CRISPR and Garlic could offer relief from climate-killing cow burps, farts
If
the researchers’ efforts are successful, they could potentially
eliminate the largest human-made source of methane and significantly
impact global warming trends. Researchers from the University of California at Davis and the
Innovative Genomics Institute are conducting a multiyear experiment to
alter the digestive processes within cow stomachs. Cows, which
are widely consumed around the world, generate significant amounts of
methane, a potent greenhouse gas that contributes to 30% of global
warming.
The team is using CRISPR technology to genetically modify microbes in
the cows’ stomachs with the goal of reducing or eliminating these
methane emissions.
“It’s completely out of the box,” said Ermias Kebreab, a professor of animal science at UC-Davis. “Nobody has done it before.”
Potential solutions from pasta ingredients?
On average, a cow emits approximately 220 pounds of methane annually,
which is about half the emissions produced by a typical car. According
to the Food and Agriculture Organization , cows are responsible for around 4% of global warming.
If
the researchers’ efforts are successful, they could potentially
eliminate the largest human-made source of methane and significantly
impact global warming trends.
While adding substances like seaweed, oregano, or garlic to cow diets can reduce methane emissions by up to 80% , this approach is only feasible for about 10% of cattle in the United States—mainly dairy cows that are fed daily.
The same situation applies globally. The remaining cattle, primarily
beef cattle, graze on pastures and feed on grass and forage.
Implementing such dietary changes for these billions of free-range
cattle would be logistically challenging.
Probiotic pills to the rescue
Methane emissions from cow burps originate from gas-producing
microbes in the cows’ digestive systems. By genetically engineering
these microbes to produce less methane, researchers aim to reduce
emissions before they are expelled.
“We’re trying to come up with a solution to reduce methane that is
easily accessible and inexpensive, without restrictions or limitations,
and that can be made available not only to California but globally,” said Matthias Hess , a professor of animal science at UC-Davis.
The scientists envision creating a type of probiotic pill that could be administered to cows at birth, potentially altering their microbiome
permanently. This approach builds on previous successes with gene
editing, such as breeding cattle without horns or with heat-resistant
slick coats.
Unlike those efforts, this project targets the microbiome itself,
offering a potential solution that could be applied across different cow
breeds.
Challenges and the road ahead
A probiotic pill designed to reduce methane emissions from cows could also boost farm productivity. Cows lose up to 12% of their energy through methane burps, and other ruminants like sheep and goats experience similar losses.
Initial trials of this probiotic will be conducted at UC Davis, where
researchers will monitor methane emissions by tracking the cows’ burps
to assess the effectiveness of the treatment.
However, there are challenges ahead. While scientists have demonstrated the ability to gene-edit
microbes, they have only been able to modify a small portion of
microbes in the cow’s gut so far. Researchers are still developing
microbial gene-editing tools and mapping the microbiome species,
effectively building their methods as they advance.
Despite these concerns, the potential benefits of microbial editing are
compelling. Methane is produced not only by cows but also by goats,
sheep, and even natural sources like Arctic permafrost and temperate
wetlands. Insights gained from this research could lead to interventions
for other animals and ecosystems, according to the researchers .
Zdroj: Interesting Engineering
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Genome of Neanderthal fossil reveals lost tribe cut off for millennia
Analysis of DNA from a Neanderthal fossil found in a French cave indicates that it belonged to a group that was isolated for more than 50,000 years
Genetic analysis of a Neanderthal fossil found in France reveals that
it was from a previously unknown lineage, a remnant of an ancient
population that had remained in extreme isolation for more than 50,000
years. This finding sheds new light on the final phase of the species’
existence.
The fossil, dubbed Thorin after a character in J.R.R. Tolkien’s The Hobbit , was discovered in 2015 at the Grotte Mandrin in the Rhône Valley in southern France when Ludovic Slimak
of the Centre for Anthropobiology and Genomics of Toulouse uncovered
some teeth in the cave’s soil. The skeleton was painstakingly excavated
over the next nine years to reveal 31 teeth, the jawbone, part of the
skull and thousands of other bone fragments.
This was an incredible discovery in itself, as remains of Neanderthals – who lived in Eurasia from around 400,000 years ago until they went extinct around 40,000 years ago – are exceedingly rate.
Even more surprising was that Thorin’s genome could be obtained from a
fragment of one of his teeth, as DNA isn’t typically preserved in warm
climates. This revealed that the fossil was from a male, but opened up a
mystery that took years to solve.
By comparing his
genome with those of other Neanderthals, Slimak and his colleagues
estimated Thorin lived around 105,000 years ago. However, archaeological
evidence and analysis of the isotopes in his bones unequivocally showed
that Thorin lived no more than 50,000 years ago – making him a “late
Neanderthal” from the final phase of the species’ existence.
“For a very long time we [geneticists] were convinced that Thorin
really was an early Neanderthal, just because his genetic lineage was so
distantly related to contemporary Neanderthals in the same region,”
says team member Tharsika Vimala
of the University of Copenhagen. “On the other side, the archaeologists
were convinced that he was a late Neanderthal. It took years of work
from both sides to get to the answer.”
Eventually, the researchers realised that they must have discovered a
hitherto unknown lineage of Neanderthals. Thorin was part of a small
group who lived between 42,000 and 50,000 years ago. The group seems to
have been a remnant of a far more ancient Neanderthal population that
diverged from the main Neanderthal population around 105,000 years ago,
and had then stayed genetically isolated for more than 50,000 years.
Thorin’s DNA showed no evidence of interbreeding between his lineage
and that of the main Neanderthal population, despite living in close
proximity. “Thorin was completely divergent from any other
Neanderthals,” says Slimak.
This isolation could have made the group particularly vulnerable.
“Long term isolation or inbreeding can be detrimental to a population’s
survival as it can reduce the genetic diversity over time, which in turn
can have negative effects on our adaptability to changing
environments,” says Vimala.
Slimak, Vimala and their colleagues then re-analysed the genome of
another Neanderthal that had lived around 43,000 years ago at Les
Cottés, France. They found traces of a “ghost population” in its DNA
from a breeding event some 15,000 to 20,000 years previously, with
another unknown Neanderthal group.
“This means that there must have been not only two populations among
late Neanderthals, but very likely three,” says Slimak. Previously it
had been thought that at the time before their extinction, the
Neanderthals were all part of one genetically similar population.
“The evidence from Grotte Mandrin is fascinating as it gives some
intriguing insights into these late Neanderthal populations and their
dynamics,” says Emma Pomeroy at the University of Cambridge.
Zdroj: New Scientist
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New method uses light to bend DNA strands for better disease understanding
Princeton
researchers developed a new tool that enables them to physically move
DNA around to study gene expression to never before seen depths. A Princeton research team has developed a groundbreaking tool to study chromosomes by physically moving DNA strands around.
Having found and turned a key, they can access the deepest mechanisms
of gene expression to find new solutions to diseases such as cancer.
According to the study, they first had to solve a longstanding
scientific mystery by identifying that chromosomes behave like elastic
and liquid. They leveraged this finding to manipulate DNA physically,
bending strands back to probe the genome.
Building on previous research with condensates, a class of membrane-less
organelles that carry out functions within the cell and then disperse,
the team figured out a way to bioengineer condensates that respond to
laser light. This enables them to pull back “the curtains,” the strands
of DNA, as the study explains.
Now, researchers
can use these liquid-like forms of matter to manipulate the structure
of the DNA to assess how that might change gene expression.
“What’s happening here is truly incredible,” said Cliff Brangwynne,
director of Princeton’s Omenn-Darling Bioengineering Institute and study
lead. “Basically, we’ve turned droplets into little fingers that pluck on the genomic strings within living cells.”
Princeton researchers have created a new tool to understand gene expression like never before.
Getting to the deepest level of a cell
Scientists are studying gene expression to increasingly new depths,
which holds promise for locating disease before it starts or the precise
mechanism that’s causing dysfunction in the first place.
However, Princeton researchers have figured out a way to play with
DNA’s very structure. They can even pull a couple of strands together
until they touch by directing condensation to specific spots on the DNA
strands. Using
laser light, principally, they could “direct their movement quickly and
precisely via surface tension-mediated forces also known as capillary
forces.”
“We haven’t been able to have this precise control over nuclear organization on such quick timescales before,” Brangwynne said in the Princeton press release. This tool provides a way to investigate gene expression in new, stunning detail and the material science of gene expression.
Could scientists play our DNA like physical symphonies?
Whereas this function may happen randomly, with this tool, they can
control the strands and observe how genes react, thereby studying the
physical material of chromosomes , a structure of DNA of thread-like strands tightly coiled around millions of proteins in the nucleus of every cell. They compare the new tool to
CRISPR technology, except it doesn’t edit the gene but opens up a new
way to understand and possibly treat certain classes of disease,
specifically related to protein imbalances, such as cancer.
With this genome -probing
technology, they can “build a map of what’s going on…and better
understand when things are disorganized, like in cancer,” as per
postdoctoral scholar Amy R. Strom.
What they don’t know yet, and what might be the next phase in their
research, is whether or not they can “control the amount of expression
by repositioning the gene.” In a groundbreaking approach that seems
almost sci-fi, researchers may soon be able to manipulate the material
of genes to address dysfunctions at their very core.
Zdroj: Interesting Engineering
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New gene therapy boosts vision up to 10,000 times in rare eye disease patients
A new gene therapy trial has showcased promise for improving vision in people with a rare genetic disease.
This gene therapy has been developed for patients with Leber
congenital amaurosis (LCA1). This genetic condition leads to major
eyesight loss in early childhood and impacts less than 100,000 people
globally.
After receiving this therapy, some study participants’ vision improved
“100 times.” Remarkably, a couple of them reported a “10,000-fold
improvement” in their vision after getting the maximum dose of this new
gene therapy.
“That 10,000-fold improvement is the same as a patient being able to
see their surroundings on a moonlit night outdoors as opposed to
requiring bright indoor lighting before treatment,” said Artur
Cideciyan, lead author and a research professor of Ophthalmology.
“One patient reported for the first time being able to navigate at
midnight outdoors only with the light of a bonfire,” said Cideciyan, who
is also co-director of the Center for Hereditary Retinal Degenerations.
The clinical trials were co-led by researchers from the Perelman School of Medicine at the University of Pennsylvania.
Therapy surgically injected
The gene therapy (ATSN-101) is specifically designed to target and correct the genetic mutation in the GUCY2D gene. This g e ne creates vision-imparting proteins. ATSN-101 is “adapted from the AAV5 microorganism.”
The Phase I/II trial enrolled 15 participants, three of whom were
pediatric patients. Patients were surgically injected under the retina
with different gene therapy dosages.
All participants suffered from “severe vision loss” — their best vision was 20/80 or worse. This means that if a person with normal vision could see an object
clearly from 80 feet away, these patients would need to move closer to
20 feet to see it clearly.
The gene treatment was shown to be both safe and effective, with
eyesight improvements beginning within a month and lasting at least a
year.
Three of the six patients who received the highest dosage were able
to navigate in various lighting conditions. Other tests used eye charts
to determine how well individuals could see faint flashes of light.
Two high-dosage participants experienced a remarkable 10,000-fold improvement in their vision.
“It is very satisfying to see a successful multi-center trial that shows
gene therapy can be dramatically efficacious,” said Cideciyan in the press release.
Zdroj: Interesting Engineering
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No lab needed: New forensic tech cuts sexual assault DNA test time to 45 mins
The researchers have introduced a novel method for separating two individuals’ DNA using a differential digestion technique combined with digital microfluidics.
Researchers have pioneered a new method to examine evidence in sexual
assault cases. This innovative technique has the potential to
significantly expedite the forensic process, cutting down on the time
required to analyze DNA evidence.
By speeding up this crucial step, the new method could help alleviate
a key concern among victims—that the forensic evidence analysis is too
slow, which often discourages them from reporting assaults.
“Faster and more accessible DNA analysis may one day enable all
sexual assault evidence to be tested (quickly), without having to go
through the many hurdles that are currently in the system,” lead author
Mohamed Elsayed told Interesting Engineering (IE).
“Our plan is to develop an instrument that will do in five minutes
what currently takes 45,” says Elsayed. “And to run many more samples
than previously.”
Reducing sample test time for sexual assault cases
Handling forensic evidence in sexual assault cases involves a
complex, multi-phase procedure. Typically, the process begins with
collecting DNA from the victim, which is then transported to a
specialized forensic laboratory where an experienced technician takes
over.
The
first task in the lab is to separate the DNA of the assailant from that
of the victim. Once this separation is achieved, the assailant’s DNA is
analyzed to help identify a potential suspect.
This entire sequence can span several days, weeks, or even longer. A
significant portion of this time is consumed by the transportation of
the evidence to the lab, and once it arrives, the speed of analysis is
influenced by the backlog of other cases awaiting examination.
The researchers concentrated on the initial and crucial
step—isolating the DNA of two individuals from a single sample. At
present, this step is performed manually by skilled experts in a
laboratory, as there is no automated method available to carry out this
task.
The technology
Elsayed and his team have introduced a novel method for separating
two individuals’ DNA using a differential digestion technique combined
with digital microfluidics. This approach addresses many of the
logistical and technical difficulties of current practices.
Elsayed explains, “Choosing to employ digital microfluidics enabled
us to automate most steps in differential digestion, drastically
reducing the amount of hands-on time required.”
“Therefore, when combining digital microfluidics with rapid DNA ,
the whole workflow is almost fully automated. The few remaining manual
steps are very simple and do not require extensive training.”
The researchers streamlined the procedure by cutting down the manual
steps needed to isolate the assailant’s DNA from thirteen to just five.
Moreover, this new technique holds the potential for a mobile
solution that could bypass the need for a traditional lab. For instance,
DNA
testing could be conducted directly at the hospital where a sexual
assault victim is taken, thereby eliminating the delays caused by
transporting the sample to a lab and waiting in line for analysis.
When asked about how extensive a training would be required for hospital
staff to conduct this test, Elsayed said, “We anticipate a few hours of
training is enough. The amount of skill required is similar to that
used in a previous study where hospital staff who were naïve to digital microfluidics ran experiments.”
Zdroj: Interesting Engineering
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First-ever 3D DNA structure of 52,000-year-old woolly mammoth assembled
The unprecedented level of structural detail was retained because the mammoth underwent freeze-drying shortly after it died.
Researchers assembled the genome and 3D chromosomal structures of a 52,000-year-old woolly mammoth, the first time ever done in ancient DNA sampling, according to a press release.
The woolly mammoth “Yuka” froze immediately after it died. The permafrost preserved its chromosomes in a state more like glass. A remarkable and unusual fossilized creature provided the most “alive” picture ever captured of ancient DNA. Most samples found are in fragments or pieces.
“Our study shows that the morphology of ancient chromosomes is preserved in mammoth permafrost samples from 52,000 years ago, enabling the genome assembly and transcriptomic analysis of extinct species,” researchers stated.
“This is a new type of fossil with a million times more sequence,” Erez Lieberman Aiden, a corresponding author of the study said. “It is also the first time a karyotype [a complete set of chromosomes] of any sort has been determined for an ancient sample.”
The study: solving an ancient puzzle Mapping the woolly mammoth’s DNA was almost like solving a puzzle with “three billion pieces,” corresponding author Marc A. Marti-Ronom analogized. Researchers had to evaluate which sections of the DNA matched up in a skin sample taken from behind its ear.
They didn’t have a picture of the completed puzzle to reference, but they could approximate it using the genomic analysis technique (Hi-C). With Hi-C analysis and DNA sequencing combined, they mapped out 28 chromosomes using the modern elephant as a model, which also has 28 chromosomes.
The first measure of cell-specific gene activity in any ancient DNA sample The most stunning aspect of the study concerns the preservation state of the fossilized chromosomes. As they “retained a huge amount of physical integrity and detail, including the nanoscale loops,” as per the press release , researchers could tell which genes were active and inactive in its skin cells. They will apply that knowledge in the next step of their research: epigenetics, or gene expression.
“For the first time, we have a woolly mammoth tissue for which we know roughly which genes were switched on and which genes were off,” corresponding author Marti-Renom says. “This is an extraordinary new type of data, and it’s the first measure of cell-specific gene activity of the genes in any ancient DNA sample.”
They offer a glance into the genome inside living cells and which genes were active. In comparison with its modern-day relatives, researchers can say that their genes had distinct patterns of behavior most likely related to its “woolly-ness” and cold tolerance.
Zdroj: Interesting Engineering
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Last common ancestor of all life emerged far earlier than thought
All life on Earth can trace its origin to LUCA, the last universal
common ancestor – and now it seems this organism may have lived a few
hundred million years after the planet formed
The organism that gave rise to all life present on Earth may have
evolved much earlier than once thought, just a few hundred million years
after the planet formed, and been more sophisticated than previous
assessments have suggested.
The DNA inside all organisms alive today, from E. coli to blue whales, has many similarities, which suggests it can all be traced back billions of years to a last universal common ancestor
– LUCA. Many efforts have been made to understand LUCA, but now a study
taking a broader approach has turned up some surprising results.
“What we’ve been trying to do is bring people representative of
different disciplines together to come up with a holistic understanding
of when LUCA existed and what its biology was,” says Philip Donoghue at the University of Bristol in the UK.
Genes that today are found in all the main branches of life may have
been passed down in an unbroken line all the way from LUCA, allowing us
to work out what genes the ancient ancestor possessed. By looking at how
those genes have changed over time, it should be possible to estimate
when LUCA was alive.
In practice, this
is much trickier than it sounds, because genes have been lost, gained
and swapped between branches. Donoghue says the team has created a
complex model that takes account of this to work out which genes were
present in LUCA. “We come out with an organism which was much more
sophisticated than many people have argued in the past,” he says.
The researchers estimate that 2600 protein-coding genes can be traced
back to LUCA, whereas some previous estimates are as low as 80. The
team also concludes that LUCA lived around 4.2 billion years ago – much
earlier than other estimates, and surprisingly close to the formation of
Earth 4.5 billion years ago. “It suggests evolving life may be simpler
than people have argued in the past because it occurred so early,” says
Donoghue.
This earlier date is partly down to what the team says is an improved
method. But it is also because that unlike others, the researchers
don’t assume that LUCA could only have existed after the late heavy bombardment ,
when Earth is thought to have been pummelled by space debris,
potentially wiping out any burgeoning life. This period has been dated
to 3.8 billion years ago, based on rocks brought back from the moon, but
there is much uncertainty about the figure, says Donoghue.
Because their reconstruction suggests that LUCA had genes for
protecting against UV damage, it is most likely that it lived at the
surface of the ocean, the researchers think. Other genes suggest LUCA
fed on hydrogen, which is in line with previous studies. It may have
been part of an ecosystem of other kinds of primitive cells that died
out, the team speculates. “I think it’s naive in the extreme to think
that LUCA would have existed on its own,” says Donoghue.
“I find this compelling from an evolutionary perspective,” says Greg Fournier
at the Massachusetts Institute of Technology. “LUCA is not the
beginning of the story of life, but just the last shared ancestor state
that we can work backwards to using genome data.”
The results also suggest LUCA had a primitive version of the
bacterial defence system known as CRISPR, to fight off viruses. “Even
4.2 billion years ago, our earliest ancestors are fighting off viruses,”
says team member Edmund Moody , also at the University of Bristol.
Peering back into the deep past is fraught with uncertainty, and
Donoghue is the first to admit that his team may have missed the mark.
“It’s almost certainly all wrong,” he says. “What we’re trying to do is
push the envelope, and create the first kind of attempt at integrating
all of the relevant evidence.”
“It won’t be the last word,” he says. “It won’t even be our last word on this topic, but we think it’s a good start.”
Patrick Forterre
at the Pasteur Institute in Paris, France, who came up with the term
LUCA, also thinks that the organisms was not living in isolation. “But
the claim that LUCA was living before the late heavy bombardment 3.9
billion years ago is completely unrealistic for me,” Forterre says. “I
am quite sure that their strategy to determine the age and gene content
of LUCA has some flaws.”
Zdroj: New Scientist
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The plague may have wiped out most northern Europeans 5000 years ago
DNA evidence from tombs in Sweden and Denmark suggests major plague
outbreaks were responsible for the Neolithic decline in northern Europe
The Neolithic culture in Europe that produced megastructures such as
Stonehenge went into a major decline around 5400 years ago. Now we have
the best evidence yet that this was due to plague.
Sequencing of ancient DNA from 108 individuals who lived in northern Europe at this time has revealed that the plague bacterium Yersinia pestis was present in 18 of them when they died.
“We think that the plague did kill them,” says Frederik Seersholm at the University of Copenhagen in Denmark.
Around 5400 years ago, the population of Europe fell sharply , particularly in northern regions. Why this happened has long been a mystery.
Over the past decade, studies of ancient human DNA have revealed that
local populations didn’t fully recover from the Neolithic decline.
Instead, they were largely replaced by other people moving in from the
Eurasian steppes. In Britain , by around 4000 years ago, for instance, less than 10 per cent of the population was derived from the people who built Stonehenge.
These studies of ancient humans also revealed several cases where the plague bacterium was present .
This suggested a potential explanation – the plague might have wiped
out Europe’s population, allowing the steppes people to move in with
little opposition.
But not everyone agreed. Occasional sporadic plague cases are to be expected and aren’t evidence of a major pandemic, argued Ben Krause-Kyora at Kiel University in Germany in 2021. These early forms of Y. pestis
were unlikely to cause a pandemic because their DNA shows they couldn’t
survive in fleas, he and his colleagues wrote. Bites from infected
fleas are the main way people contract bubonic plague, the form of the
illness that killed people during the medieval Black Death .
So Seersholm and his colleagues set out to find more evidence of a
plague pandemic. The 108 individuals whose DNA his team managed to
sequence were buried in nine tombs in Sweden and Denmark. Most died
between 5200 and 4900 years ago, and they represent several generations
of four families.
There seem to have been three separate outbreaks of the plague over
these generations. The last outbreak was caused by a strain with
reshuffled genes that might have been much more dangerous.
“It’s present in a lot of individuals,” says Seersholm. “And it’s all
the same version, which is exactly what you would expect if something
spreads very quickly.”
The plague DNA was found mainly in teeth, which shows that the
bacterium entered the blood and caused serious illness, and was probably
the cause of death, he says. In some cases, closely related individuals
were infected, implying person-to-person spread.
The team suggests this could be a result of Y. pestis infecting the lungs and spreading via droplets – a form of the illness known as pneumonic plague . Recent studies also indicate that human lice can cause bubonic plague , not just fleas, so it is possible that plague bacteria spread by this route.
“Of course, it’s worth noting that all of these individuals were
buried properly,” says Seersholm, so society hadn’t broken down at this
time. “If there was in fact an epidemic, we only see the very beginning
of it.”
After about 4900 years ago, the megalithic tombs
seem to have been abandoned for centuries. But 10 of the sequenced
individuals were buried in them much later, most between 4100 and 3000
years ago. These individuals were of steppes origin, unrelated to those
who built the tombs.
“It is 100 per cent complete replacement,” says Seersholm. “Five
thousand years ago, these Neolithic people disappear. And now we show
that plague was widespread and abundant at exactly the same time.”
The researchers aren’t claiming their findings are definitive, but
they do bolster the case that plague caused the Neolithic decline, says
Seersholm.
“I would say that we’ve definitely shown that it had the potential to
spread within humans, and that it had the potential to kill an entire
family, for example.”
Krause-Kyora accepts that the findings show the plague was highly
prevalent in this particular place and time. “Our previous explanation
needs to be revised somewhat, and we can’t just talk about isolated
cases,” he says.
But there is no evidence of high prevalence in other regions, he
says. And he thinks the normal burials show there was no deadly
epidemic. “The results could even suggest that the Yersinia infection was more of a chronic disease over a long period of time.”
Seersholm and his team will now look for more evidence elsewhere in
Europe. But the only way to know for sure how deadly the reshuffled
strain was would be to bring it back to life, he says, and that is far
too risky to attempt.
“I think that this paper will convince many colleagues who were skeptical about our previous work,” says Nicolás Rascovan
at the Pasteur Institute in Paris, whose team proposed in 2018 that the
plague was responsible for the Neolithic decline after finding it in
two individuals from the period.
Zdroj: New Scientist
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'Bridge editing' could be even better at altering DNA than CRISPR
The CRISPR gene-editing technique has revolutionised biology, but now an even more powerful system called bridge editing could let us completely reshape genomes A powerful form of DNA-editing machinery discovered in bacteria might allow us to make much bigger changes to genomes than is currently possible with CRISPR-based techniques. However, it isn’t yet clear whether it will work in human cells. Patrick Hsu at the Arc Institute in California calls the new genome editor the “bridge editing” system because it physically links, or bridges, two pieces of DNA . It can be used to alter huge sections of a genome, says Hsu, whose team worked out how sequences of “parasitic” DNA in bacteria naturally use the system to replicate, and how it might be adapted for genome editing. “We’re excited about the potential to do much broader genomic changes beyond what we can currently do with CRISPR,” he says. “We think this is an important step towards the broader vision of genome design.” CRISPR gene editing has revolutionised biology since it was unveiled in 2012. It is being used for many different purposes, and the first CRISPR-based treatments were approved last year. However, the basic form of CRISPR, which uses the Cas9 protein, is more of a gene destroyer than a gene editor. There are two parts to the standard CRISPR Cas9 protein. One part links up with a guide RNA molecule and seeks out any DNA that matches a certain section of the guide RNA. Because it is easy to make custom guide RNAs, this means that CRISPR Cas9 can be “programmed” to seek out any part of the genome. The second part of CRISPR Cas9 is a cutter that severs DNA once the Cas9 has bound to its target site. The cell repairs the damage and the Cas9 cuts it again, and this keeps happening until mistakes are made during the repairs, mutating the target site in a directed way. While being able to mutate specific sites is useful, biologists would prefer to make more precise changes, so they have been modifying CRISPR proteins to edit DNA directly instead of relying on cell repair mechanisms. Base editors, for instance, can change a single DNA letter to another without cutting the DNA. Prime editors, meanwhile, can turn an extra section of guide RNA into DNA and add it to the target site. These modified forms of CRISPR could help treat a huge range of conditions and several human trials are already under way, but tackling some diseases requires more advanced genome alterations. Lots of teams around the world are working on ways of doing this. Some realised that the mechanism used by genetic parasites called IS110 elements to cut and paste themselves from one part of a genome to another had potential, because it is RNA-guided like CRISPR, but Hsu’s team is the first to get the complete picture of how it works. The bridge-editing system consists of a so-called recombinase protein that hooks up with a guide RNA, like the CRISPR Cas9 protein. What makes it unique is that the guide RNA specifies two DNA sequences to seek out, not just one, Hsu’s team discovered. One sequence specifies the target site in the genome to be altered, just as in CRISPR, while the other specifies the DNA to be altered. This system can be used to add, delete or reverse DNA sequences of virtually any length. There are already ways of doing this, but they typically involve multiple steps and leave extra bits of DNA, called scars, behind. “Bridge editing is effectively scarless,” says Hsu. “It offers an unprecedented level of control for manipulating genomes.” This means it could be used to do far more than simply replace faulty genes, he says. It could also help us completely reshape the genomes of plants and animals. “What we’d like to do is to move beyond inserting individual genes to do chromosome-scale genome engineering,” says Hsu. “The discoveries reported are indeed exciting, and the underlying biology is truly remarkable,” says Stephen Tang at Columbia University in New York, but so far bridge editing has only been shown to work in bacterial cells or in test tubes. It remains to be seen whether and how well it will work in complex cells like those of humans, says Tang. But even if bridge editing fails to work in initial tests in human cells, it’s likely that in time the system can be modified so it does work.
Zdroj: New Scientist
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‘Powerhouse’ gene to fight obesity discovered by scientists in China
Genetic study suggests evolutionary advantages of M7b1a1 subgroup in combating obesity risks.
Chinese researchers have found a gene that might help people resist obesity, a major health problem worldwide.
This discovery could help us better understand how genes influence
obesity. It might also lead to new ways to treat and prevent the
condition.
Obesity is a big health problem worldwide and is connected to serious
issues like heart disease and type 2 diabetes. As medical research
progresses, we are learning more about obesity. This includes
understanding its many effects on health.
Despite rapid economic development, China still boasts one of the lowest obesity rates globally. A 2022 study in The Lancet found that Chinese women rank 190th and Chinese men 149th in the world for obesity rates.
Genetic factors in obesity resistance
Although diet and economic development are important, new research
led by Professor Jin Li and Associate Professor Zheng Hongxiang from
Fudan University shows that genetics could also be very important in how
some people avoid becoming obese. Their study analyzed 2,877 samples
from populations in Guangxi, Jiangsu, and Henan, as reported by South China Morning Post (SCMP ).
The researchers found a kind of mitochondrial DNA (mtDNA) that is
common in southern China and Southeast Asia and that seems to help
protect against obesity.
“Mitochondria are often referred to as the cell’s powerhouses,
generating 80 to 90 percent of the energy needed for various human
behaviors. Mitochondrial function has long been associated with
obesity,” Jin explained.
Unlike nuclear DNA ,
which is inherited from both parents, mtDNA is typically passed down
only from the mother. It is more prone to genetic mutations useful in
evolutionary analysis.
Jin and his team conducted association analyses of 16 basal
mitochondrial DNA haplogroups, genetic families tracing back to a common
ancestor. They found that a specific variant group, named M7, was
consistently linked to a reduced risk of obesity . Further analysis pinpointed a subgroup, M7b1a1, as the most likely source of this protective effect.
In 2019, Professor Kong Qingpeng from the Chinese Academy of Sciences published a study in Molecular Biology and Evolution .
It showed that the M7b1a1 subgroup is mostly found in southern China
and mainland Southeast Asia. This subgroup is also found in 5 to 14
percent of southern Han Chinese people.
Evolutionary advantages and future applications
The researchers believe that decreased mitochondrial function may explain why M7b1a1 reduces obesity
risk. “Decreased mitochondrial functions represent less energy
conservation and more heat production, which could result in less weight
gain,” Jin wrote in the study.
The team also discovered that M7b1a1 appears to have undergone population expansion approximately 15,000 years ago.
Jin suggests that this historical expansion supports their
hypothesis, “M7b1a1 carriers with greater heat generation may have
adapted to the cold climate in the Ice Age well, which may have been
evolutionarily advantageous for positive natural selection.”
These findings provide a new way to look at how genes affect traits
related to obesity. Jin and his team think their research could help
develop new ways to fight obesity by studying genes and how mitochondria
work.
The study was published in the peer-reviewed Journal of Genetics and Genomics .
Zdroj: Interesting Engineering
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99% gene transmission possible, China’s CRISPR tool boosts food security
The
innovation, known as CRISPR-Assisted Inheritance (CAIN), can increase
gene transmission rates up to 99% in just two generations! Chinese
scientists have engineered a solution by which they could bypass
natural plant gene inheritance. They aim to deploy a CRISPR-based gene
editing system to help the transmission of preferred genes even when
they aren’t suitable for a plant.
The scientists devised a system that would use both a toxin and an
antidote which would directly affect the male plant germline. Through
this process, the researchers could overcome the natural Mendelian
transmission rate. This can help increase the gene transmission rates up
to 99% over two generations.
Genetic manipulation helps tackle food security challenges
The team published their findings in Nature Plants, a peer-reviewed journal, and highlighted that food security has
been a multifaceted challenge for a long, especially from agricultural
weeds. The issue has been exacerbated by agricultural weeds and the
environmental crisis of invasive plants.
“The genetic manipulation of wild plant populations has emerged as a
potentially powerful and transformative strategy” the team proposed.
However, traditional breeding for ideal genes can be problematic for
plants, especially those constrained by Mendelian inheritance and
Darwinian natural selection. The former describes how genetic traits are
passed down through generations.
“Synthetic gene drives, inspired by natural selfish genetic elements
and transmitted to progeny at super-Mendelian (greater than 50 per cent)
frequencies, present transformative potential for disseminating traits
that benefit humans throughout wild populations, even facing potential
fitness costs,” the team added.
The team also constructed a gene-driving system called CRISPR-Assisted Inheritance using the NPG1 (CAIN) method.
CAIN method: Revolutionizing gene transmission through toxin-antidote strategy
The CAIN method utilizes a toxin-antidote strategy in the male
germline to bypass traditional Mendelian inheritance. A guide Cas9
cassette disrupts the NPG1 gene, inhibiting pollen germination.
Subsequently, a CRISPR-resistant “antidote” copy of NPG1 rescues pollen cells carrying the desired gene drive.
“CAIN transmission rates greatly exceeded the expected Mendelian
inheritance of 50 per cent in heterozygous male parents, reaching 88 to
99 per cent within two successive generations,” the team wrote.
“We established CAIN as a state-of-the-art tool to efficiently modify entire plant populations.”
Balancing crop protection with sustainability using CAIN
CAIN helps in developing a higher amount of resistance alleles. The
researchers targeted the male germline due to the fertility limitations
of toxin-antidote gene drives targeting the female germline.
“This gene drive -based
approach thus seeks to balance crop protection and environmental
considerations to minimise the loss of biodiversity while optimising
productivity,” the researchers wrote.
China has long advocated for seed source independence and emphasized sustained efforts to achieve China’s food security.
“As we venture into this new frontier in genetic engineering, [CAIN]
and other gene drive systems could reshape ecological management and
agricultural practices,” the researchers concluded.
Zdroj: Interesting Engineering
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Wearable ultrasound? New tech targets trouble spots in the brain
Sonogenetics provides researchers with a precise method to control brain activity. Researchers at Washington University in St. Louis have innovated a
noninvasive technology that merges a holographic acoustic device with
genetic engineering . This enables them to target specific neurons within
the brain accurately.
This breakthrough holds promise for the precise modulation of targeted cell types across various diseased brain regions.
Diseases of the human brain, such as Parkinson’s, affect multiple
regions, necessitating technology capable of precisely and flexibly
addressing all impacted areas simultaneously.
“By enabling precise and flexible cell-type-specific neuromodulation
without invasive procedures, AhSonogenetics provides a powerful tool for
investigating intact neural circuits and offers promising interventions
for neurological disorders,” Hong Chen, an associate professor of
biomedical engineering at the McKelvey School of Engineering and of
neurosurgery at the School of Medicine, said.
A noninvasive wearable ultrasound device
Chen and her team developed a technique called AhSonogenetics, or
Airy-beam holographic sonogenetics. This method employs a noninvasive
wearable ultrasound device to modify genetically selected neurons in
mouse brains.
AhSonogenetics integrates several of Chen’s group’s recent
breakthroughs into a single technology. In 2021, Chen and her team
introduced Sonogenetics, a method utilizing focused ultrasound to
deliver a viral construct containing ultrasound-sensitive ion channels
to genetically selected neurons in the brain
This technique employs low-intensity focused ultrasound
to produce a brief burst of warmth, opening the ion channels and
activating the neurons. Chen’s team was the first to demonstrate that
sonogenetics could influence the behavior of freely moving mice.
In 2022, Chen and her lab members designed and 3D-printed a flexible
and versatile device called an Airy beam-enabled binary acoustic
metasurface, which allowed them to manipulate ultrasound beams.
Additionally, she is working on Sonogenetics 2.0, a technique that
combines the benefits of ultrasound and genetic engineering to
noninvasively and precisely modulate specific neurons in the brains of
humans and animals.
Sonogenetics: The tech behind the device
Sonogenetics provides researchers with a precise method to control
brain activity, while airy-beam technology enables the bending or
steering of sound waves to create arbitrary beam patterns within the brain with high spatial resolution.
According to Yaoheng Yang, a postdoctoral research associate who
earned his doctorate in biomedical engineering from McKelvey Engineering
in 2022, this technology offers three distinct advantages to
researchers.
“Airy beam is the technology that can give us precise targeting of a
smaller region than conventional technology, the flexibility to steer to
the targeted brain regions, and to target multiple brain regions
simultaneously,” Yang said .
Chen and her team, including first authors Zhongtao Hu, a former
postdoctoral research associate, and Yaoheng (Mack) Yang, individually
designed each Airy-beam metasurface to serve as the basis for wearable
ultrasound devices tailored for various applications and precise brain
locations.
The team tested the technique on a mouse model of Parkinson’s
disease. Using AhSonogenetics, they successfully stimulated two brain
regions simultaneously in a single mouse, removing the need for multiple
implants or interventions. This stimulation alleviated Parkinson’s -related motor deficits in the mouse model, such as slow movements, difficulty walking, and freezing behaviors.
Zdroj: Interesting Engineering
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Study explores how Neanderthal’s Y chromosome didn’t pass over to humans
Genetic studies suggest a rapid influx of Neanderthal genes into Homo sapiens roughly 47,000 years ago. Native American recently went viral after discovering unusual amount
of Neanderthal in his DNA which sparked renewed interest about our
ancient genetic roots as several human groups existed in “the land
before time.”
A professor at the University of Pennsylvania even told Newsweek
at the time that the interbreeding of human species still remains an
untapped area of research. To make a real conclusion, he said, we need
to investigate further and then, a study was published shortly
thereafter.
It turns out, the young man who went viral isn’t even that rare. Most
of us seem to have a little Neanderthal across our DNA . Research seems
to suggest that we split — homo sapiens and Neanderthals — over 500,000
years ago to reunite later on as the two groups migrated to other
continents.
Most of the Neanderthal DNA
that modern humans have, however, it turns out, traces back to a
specific moment in time about 47,000 years ago, according to a study reported in Science, when the two groups got together and made babies.
In analyzing the DNA
of both species, we basically have the same genetic code, except the
Neanderthal Y chromosome doesn’t seem to appear our DNA as The Conversation reported. Though we have a similar blueprint, then, the lack of this gene in our DNA raises questions.
The story behind the X and the Y chromosomes
Usually, males have one X and one Y, and females have two X
chromosomes. Sometimes a person can be born with more or less sex
chromosomes which tends to lead to complications for reasons that we
don’t totally understand.
That aside, we all get some combination of the X from the male or
female parent. The Y, however, only comes from the male. Because of
that, the absence of this Neanderthal chromosome might provide a clue of
some kind.
But then, to even out the playing field, no trace of Neanderthal
mtDNA has been found in modern humans either which comes directly from
the maternal line, so it seems these cycled out for some reason.
The Y plays an important role in biological sex and male fertility, according to a study . While mtDNA can provide some health insights, its overall implications remain unclear.
Some genetic combinations might not work, why? We don’t know…
The manner in which these two groups united for breeding remains uncertain, with little studied in this aspect of our history.
The Natural Museum published an article about a paper written about whether homo sapiens might have brought about the extinction of Neanderthals through sex which might have reduced the number of Neanderthals breeding with one another.
As other species demonstrate, some directions just don’t work.
“For instance, pollen from the Capsella rubella plant can successfully fertilise Capsella grandiflora seeds, but not the other way round.”
The Natural Museum says that the lack of mtDNA might mean that only male Neanderthals and female homo sapiens mated, but some evidence seems to suggest that “male hybrids might have been less fertile than females.”
The Y evolves faster according to The Conversation and
is related to male fertility, maybe these hybrid male offspring did
experience issues due to the genetic meeting of the two groups.
“As more Neanderthal genomes are sequenced, ”
however, the author of a paper on the subject of mating between the two
groups said that “we should be able to see whether any nuclear DNA
from Homo sapiens was passed on to Neanderthals and demonstrate whether or not this idea is accurate.”
Zdroj: Interesting Engineering
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Japanese researchers use body’s own genes to treat rare skin disorders
Skin
diseases like epidermolytic ichthyosis (EI) and ichthyosis with
confetti (IWC) are now treatable through healthy skin transplantation. With recent advancements in science and technology, skin diseases can now be treated by transplanting healthy skin.
Researchers from Nagoya University Graduate School in Japan have been
successful in treating skin diseases. They are epidermolytic ichthyosis
(EI) and ichthyosis with confetti (IWC).
They achieved this by transplanting genetically healthy skin to
inflamed areas. As of now, transplanting healthy skin to inflamed areas
would be mostly used as a treatment option to tackle severe burn
injuries.
Now, the researchers applied this technique to make sure that skin ailments
are cured. It’s believed that this research could call for a new and
effective solution for those with challenging skin disorders.
Understanding EI and IWC – rare skin disorders
The study notes that EI and IWC are genetic disorders which are
extremely rare. These are mostly caused by mutations in one of the two
genes which make keratin in the skin .
In order to maintain skin integrity keratin plays an important role.
But these mutations can often form fragile skin with blisters, and thick
and scaly patches. These skin conditions have been found in a number of
patients. They showcased large patches of healthy skin in the affected
areas.
Called somatic recombination this is a process where random genetic
changes refine the mutations. They do so by altering the genes that
cause this skin condition. As a result of this, the skin can now return
to a healthy state.
There have been reports in the past where scientists have been able to
treat a kid. He had a rare genetic skin disease. They did this through a
transplant of skin grown using genetically modified stem cells as
reported by CNN .
Harnessing somantic recombinations for treating skin diseases
Lecturer Kana Tanahashi, Prof. Masashi Akiyama, and Associate Prof.
Takuya Takeich led the research and they realised that they could use
semantic recombinations for a pioneering therapy .
They tried making grafts which are called “cultured epidermal
autografts” (CEAs) containing genetic mutation corrections to give
healthy skin.
They could also graft these naturally corrected skin cells in the affected areas, and control the outbreaks of these diseases.
Milestones in skin disease treatment
The researchers tried evaluating the feasibility of transplanting
CEAs. These were derived using revertant epidermal keratinocytes —those
that lack the keratin mutation— back onto patients. After this, these
CEAs were transplanted into the peeling lesions of the patients.
After a month two of the patients had no ichthyosis recurrence in the
entire treated area. The third did not show recurrence in more than a
third (39.52%) of the affected area.
Successful in the initial days, almost 24 weeks after the
transplantation all three patients had experienced some recurrence of
ichthyosis at the transplant sites. In the end, the researchers said
that this technique could be best used to get rid of symptoms.
This would be especially applicable during severe conditions and also to treat local EI symptoms in specific regions.
This marks a milestone in the treatment of EI and IWC. Naturally,
genetic correction mechanisms of the body have led researchers to
showcase a novel and promising treatment. This study paves the way for
even more studies that would be more beneficial to patients in the long
run.
The study was published in the British Journal of Dermatology .
Zdroj: Interesting Engineering
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How starchy foods shaped human genomes
Starchy foods have played a pivotal role in human evolution, influencing not only our diets but also our genetic makeup.
A
recent study has revealed that the rise of agriculture – around 12,000
years ago – and the subsequent increase in starchy staples like wheat
and grains, significantly impacted the human genome.
Researchers from the United States, Italy, and the United Kingdom
found that our ability to digest carbohydrates has significantly evolved
over time. This is closely linked to the rise of agriculture and the
increase of starchy foods in our diets.
The evolutionary power of starchy foods The
ability to extract energy from starchy foods has increased remarkably
during this period, as shown by an expansion in the number of genes
encoding enzymes that break down starch – jumping from an average of
eight to over 11.
“The copy number of amylase genes had increased
in Europeans since the dawn of agriculture, but we had never been able
to sequence this locus fully before. It is extremely repetitive and
complex,” said Peter Sudmant, assistant professor of integrative biology
at the University of California, Berkeley , and one of the lead authors of the study.
This
increase in amylase genes closely matched the rise and spread of
agriculture across Europe from the Middle East, aligning with changes in
dietary patterns.
Decoding the amylase locus The
researchers meticulously examined the genome’s amylase locus, where the
salivary amylase gene (AMY1) and two pancreatic amylase genes (AMY2A
and AMY2B) reside.
“If you take
a piece of dry pasta and put it in your mouth, eventually it’ll get a
little bit sweet. That’s your salivary amylase enzyme breaking the starches down into sugars,” explained Sudmant.
While this happens in all humans and other primates, the human genome
contains a significantly higher number of amylase gene copies compared
to our primate relatives, such as chimpanzees and Neanderthals, who
possess only a single copy of AMY1.
UC Berkeley postdoctoral
fellow Runyang Nicolas Lou, one of the study’s co-authors, elaborated:
“Our study found that each copy of the human genome harbors one to 11
copies of AMY1, zero to three copies of AMY2A, and one to four copies of
AMY2B. Copy number is correlated with gene expression and protein level
and thus the ability to digest starch.”
Survival advantage and global adaptation The
presence of multiple amylase genes provided a survival advantage, with
the incidence of chromosomes carrying multiple copies increasing
sevenfold over the last 12,000 years.
This evolution was not
confined to Europe. The researchers found evidence of similar patterns
in other agricultural populations globally, regardless of which starchy plant was domesticated.
Erik Garrison, a co-lead author from the University of Tennessee Health Science Center ,
highlighted the broader implications of the findings: “One of the
exciting things we were able to do here is probe both modern and ancient
genomes to dissect the history of structural evolution at this locus.”
The dawn of a new method Another
breakthrough in the study was the development of a new method for
identifying diseases involving genes with multiple copies, like amylase.
This method also opens doors to exploring rapidly duplicating genes
related to the immune system, skin pigmentation, and mucus production.
The
research hints at a potential link between higher AMY1 copies and
increased tooth decay, though further investigation is needed.
Joana
Rocha, a co-author from UC Berkeley, compared the genomic structure of
the amylase locus to “sculptures made of different Lego bricks.”
Long-read
sequencing techniques allowed the team to reconstruct these complex
genetic structures with unprecedented accuracy, shedding light on human
evolutionary history and its genetic diversity.
This research,
funded by the U.S. National Institutes of Health, is part of an
expanding effort to better understand how genetic adaptations have
shaped human health and disease through our changing diets over millennia.
Starchy foods and human health The evolutionary relationship between starchy foods and human genetics continues to shape modern health.
As
our ancestors adapted to carbohydrate-rich diets, today’s populations
still show varying abilities to digest starch, potentially influencing
susceptibility to conditions such as obesity and diabetes.
Understanding
this genetic adaptation to starchy foods not only offers insights into
our past but also provides valuable information for addressing
contemporary health challenges linked to diet and metabolism.
The study is published in the journal Nature .
Zdroj: web
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Gene therapy enables five children who were born deaf to hear
Five children in China who were born deaf can now hear with both ears after getting gene therapy to provide a normal copy of a mutated gene. The degree of hearing varies from child to child, but all can now hear voices at a conversational volume and locate the source of sounds. Six months after treatment, the five children’s hearing was around 50 to 60 per cent of normal levels, says team member Zheng-Yi Chen at the Mass Eye and Ear hospital in Boston. “When we whisper, they have a difficult time, but normal conversation is fine,” he says. “We’re very happy.”
In the first part of this trial, which began in 2022, the team gave a separate group of six children in China gene therapy in one ear only. Five of the six gained hearing in the treated ear and are still continuously improving, says Chen.
The team expects the second group of five children to see further gains too. “What we see now is not the peak of the improvement,” says Chen. “We expect it to improve further.”
The trial in China is the first of several getting under way around the world, with two children in the UK and one in the US also reported to have gained hearing in one ear after receiving gene therapy.
“The trials are all broadly similar,” says Manohar Bance at the University of Cambridge, who treated the two children in the UK.
All the children in these trials were born deaf because they have mutations in both copies of the gene for a protein called otoferlin. This plays a key role in the synapses, or links, between the hair cells in the ear that detect sound and the nerves that carry the signals to the brain. The mutations affect the protein, stopping the signals from being transmitted.
Between 2 and 8 per cent of the children born deaf around the world are thought to have this condition, known as DFNB9.
The parents of children with DFNB9 have normal hearing if they each have just one mutated copy of otoferlin. Such couples are usually unaware they have a 1 in 4 chance of having a child who is born deaf.
The gene therapy involves delivering a working version of the otoferlin gene to the hair cells with the help of a virus called AAV. Because of the size of the otoferlin gene, it has to be split and put into two separate viruses .
A mixture of the viruses is injected into the inner ear and the complete gene is then reassembled inside cells that get both of its halves. The DFNB9 trials are the first time that dual AAV gene therapy, as it is known, has been used to treat people.
“This is a big technological advancement,” says Chen. “We expect to see very broad use of the technology for treating other genetic diseases.”
The trials start by treating just one ear at a time because this requires half the dose of AAV, he says, reducing the odds of any adverse events. No serious adverse events have been reported in any of the trials.
Chen’s team now plans to treat the other ear of the children in the first group. This might be tricky because the immune response to the initial AAV injection could block gene delivery, but Chen thinks it will be possible.
Treating other forms of inherited deafness will be harder, says Chen, because these result in the degeneration of some structures within the ear. With DFNB9, all the structures remain intact. “We just need to fix one component,” he says.
Some people don’t see deafness as a condition that needs to be cured , says Martin McLean at the UK’s National Deaf Children’s Society. The society’s position is that families should be free to make informed decisions for themselves .
“Parents or young people should be made aware of any risks, and above all understand that being deaf is not a barrier in itself to a happy and fulfilled life,” he says.
Zdroj: New Scientist
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Chinese scientists create 90% lethal Ebola-like virus to study eye disorders
Scientists are optimistic that this new model could help in future research on Ebola-related eye disorders. Chinese scientists have genetically modified a virus that imitates
Ebola infection. This virus has caused severe eye ulcers and ultimately
wiped out an entire group of hamsters.
Researchers are hopeful that this study will aid in the research of Ebola-related eye disorders.
In this study, vesicular stomatitis, typically found in livestock,
was harboring the Ebola virus. When they gave it to the hamsters, the
entire group died after the ulcers in their eyes worsened.
New model reveals promising insights into Ebola virus research
Vesicular stomatitis (VSV), carries a part of the Ebola virus called
glycoprotein (GP). It helps the virus to enter and infect the cells.
Five female and five male hamsters that were up to three weeks old died
within three days.
They showed symptoms similar to those in Ebola patients, such as
weight loss, multi-organ failure, severe eye inflammation, and ulcers.
Additionally, the hamsters had high levels of the virus in their bodies.
Scientists are optimistic that this new model could help in future
research on Ebola-related eye disorders. “All animals died within 2-3
days after infection,” the researchers observed, noting that this model
could be useful for testing Ebola vaccines.
According to the scientists, this model allowed for quick preclinical
testing of Ebola virus countermeasures in BSL-2 conditions.
They added, “This surrogate model is a safe, effective, and
cost-efficient tool for rapid preclinical evaluation of medical
countermeasures against the Ebola virus under BSL-2 conditions. It has
the potential to accelerate technological advances and breakthroughs in
combating Ebola virus disease.”
More accessible to researchers for studying
The Ebola virus causes internal bleeding and tissue damage and is
spread by direct contact with infected body fluids, such as blood or
sweat, or by touching contaminated objects. This is significant because
studying Ebola requires expensive and high-level biological security,
like that in BSL-4 facilities.
As a result, the virus has been less accessible to scientists.
According to the scientists, the development of countermeasures against
EBOV has been hindered by the lack of ideal animal models. The reason
was that EBOV requires handling in BSL-4 facilities.
In the study,
they also analyzed the influence of the virus. They found that the
virus had accumulated in critical tissues. Like for example the heart,
lungs, liver, spleen, kidneys, intestines, and brain. As the study
showed, the highest viral loads were found in the liver, and the lowest
levels were found in the brain.
Lab leak?
Dr Richard Ebright, a chemical biologist at Rutgers University in New Jersey told DailyMail.com that it is unlikely that a lab leak involving VSV would lead to widespread infection in the public.
“[It] will be imperative to verify that the novel chimeric virus does
not infect and replicate in human cells, and does not pose risk of
infectivity, transmissibility, and pathogenicity in humans, before
proceeding with studies at biosafety level 2,” he concluded.
Ebola is caused by a group of viruses, known as orthoebolaviruses.
They were discovered in 1976 in the Democratic Republic of the Congo.
Since Ebola was first identified in 1976, there have been 29 outbreaks
or case reports of Ebola virus disease.
According to the WHO, the 2014–2016 outbreak in West Africa was the
largest and most complex Ebola outbreak, with 28 646 reported cases and
11 323 reported deaths.
Zdroj: Interesting Engineering
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Bringing back an ancient bird
Using ancient DNA extracted from the toe bone of a museum specimen,
Harvard biologists have sequenced the genome of an extinct, flightless
bird called the little bush moa , shedding light into an unknown corner of avian genetic history.
Published in Science Advances ,
the work is the first complete genetic map of the turkey-sized bird
whose distant living cousins include the ostrich, emu, and kiwi. It is
one of nine known species of moa, all extinct for the last 700 years,
that inhabited New Zealand before the late 1200s and the arrival of
Polynesian human settlers.
“We’re pulling away the veil across the mystery of this species,” said senior author Scott V. Edwards , professor in the Department of Organismic and Evolutionary Biology and curator of ornithology at the Museum of Comparative Zoology.
“We can study modern birds by looking at them and their behavior. With
extinct species, we have very little information except what their bones
looked like and in some cases what they ate. DNA provides a really
exciting window into the natural history of extinct species like the
little bush moa.”
Bush moa were the smallest of the moa species, weighing about 60
pounds and distributed in lowland forests across the north and south
islands of New Zealand. Genomic analysis has revealed their closest
living relatives aren’t kiwis, as was originally speculated, but rather tinamous , a Neotropical bird group from which they diverged genetically about 53 million years ago.
The Harvard team offers new genetic evidence for various aspects of
bush moa sensory biology. Like many birds, they had four types of cone
photoreceptors in their retinas, which gave them not only color but also
ultraviolet vision. They had a full set of taste receptors, including
bitter and umami. Perhaps the most remarkable trait of these flightless
birds is their complete absence of forelimb skeletal elements that
typically comprise birds’ wings, the researchers wrote. Studying the moa
genome could offer new clues into how and why some birds evolved to
become flightless.
The scientists used high-throughput DNA sequencing , which allows
rapid sequencing of short DNA fragments of only 101 nucleotide base
pairs and the building of libraries with millions of these genetic
sections. To produce the bush moa genome, the team sequenced the
equivalent of 140 bird genomes, or about 140 billion base pairs of DNA,
only about 12% of which was actual moa DNA (the rest was bacterial).
They then assembled the genome, taking each snippet of DNA and
mapping it to its correct position. Genome assembly of extinct species
is painstaking work that is made more accessible through technologies
like high-throughput sequencing. Other species that have been mapped
similarly are the passenger pigeon, the woolly mammoth, and our close
relative, the Neanderthal. Using an existing emu genome as a guide, they
strung together the bush moa’s genetic sequence by finding overlaps
between each genetic snippet, essentially reconstructing a long puzzle
of 140 billion pieces.
The bush moa project originated more than 15 years ago in the lab of
the late Allan J. Baker, an expert in ancient bird DNA at the Royal
Ontario Museum who first extracted and sequenced the bird’s DNA from a
fossil recovered on the South Island of New Zealand. Also involved in
the initial DNA processing and sequencing was co-author Alison Cloutier,
who formerly worked with Baker and later became a postdoctoral
researcher in Edwards’ lab at Harvard which inherited the data.
Reconstructing the genome of a long-extinct bird fills in a new
branch of the avian family tree, opening doors to study avian evolution,
or even someday, to possibly resurrect these species through
de-extinction technologies.
“To me, this work is all about fleshing out the natural history of this amazing species,” Edwards said.
Zdroj: web
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Ancient Viruses Linked to Mental Illness
Summary: A new study reveals that ancient viral DNA sequences, once thought to be “junk DNA,” are active in the human brain and contribute to the risk of psychiatric disorders like schizophrenia, bipolar disorder, and depression. This discovery sheds light on the complex genetic factors influencing mental health.
Key Facts:
Ancient viral DNA sequences are expressed in the human brain. Some of these sequences are linked to increased risk for psychiatric disorders. Understanding these ancient viruses could revolutionize mental health research and treatment. Source: King’s College London
New research led by King’s College London has found that thousands of DNA sequences originating from ancient viral infections are expressed in the brain, with some contributing to susceptibility for psychiatric disorders such as schizophrenia, bipolar disorder, and depression.
Published in Nature Communications , the study was part-funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre and the US National Institutes of Health (NIH).
About eight percent of our genome is comprised of sequences called Human Endogenous Retroviruses (HERVs), which are products of ancient viral infections that occurred hundreds of thousands of years ago.
Until recently, it was assumed that these ‘fossil viruses’ were simply junk DNA, with no important function in the body.
However, due to advances in genomics research, scientists have now discovered where in our DNA these fossil viruses are located, enabling us to better understand when they are expressed and what functions they may have.
This new study builds upon these advances and is the first to show that a set of specific HERVs expressed in the human brain contribute to psychiatric disorder susceptibility, marking a step forward in understanding the complex genetic components that contribute to these conditions.
Dr Timothy Powell, co-senior author on the study and Senior Lecturer at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, said: “This study uses a novel and robust approach to assess how genetic susceptibility for psychiatric disorders imparts its effects on the expression of ancient viral sequences present in the modern human genome.
“Our results suggest that these viral sequences probably play a more important role in the human brain than originally thought, with specific HERV expression profiles being associated with an increased susceptibility for some psychiatric disorders”.
The study analysed data from large genetic studies involving tens of thousands of people, both with and without mental health conditions, as well as information from autopsy brain samples from 800 individuals, to explore how DNA variations linked to psychiatric disorders affect the expression of HERVs.
Although most genetic risk variants linked to psychiatric diagnoses impacted genes with well-known biological functions, the researchers found that some genetic risk variants preferentially affected the expression of HERVs.
The researchers reported five robust HERV expression signatures associated with psychiatric disorders, including two HERVs that are associated with risk for schizophrenia, one associated with risk for both bipolar disorder and schizophrenia, and one associated with risk for depression.
Dr Rodrigo Duarte, first author and Research Fellow at the IoPPN, King’s College London, said: “We know that psychiatric disorders have a substantial genetic component, with many parts of the genome incrementally contributing to susceptibility.
“In our study, we were able to investigate parts of the genome corresponding to HERVs, which led to the identification of five sequences that are relevant to psychiatric disorders.
“Whilst it is not clear yet how these HERVs affect brain cells to confer this increase in risk, our findings suggest that their expression regulation is important for brain function.”
Dr Douglas Nixon, co-senior author on the study and and researcher at the Feinstein Institutes for Medical Research at Northwell Health, in the US, said: “Further research is needed to understand the exact function of most HERVs, including those identified in our study.
“We think that a better understanding of these ancient viruses, and the known genes implicated in psychiatric disorders, have the potential to revolutionise mental health research and lead to novel ways to treat or diagnose these conditions”.
Abstract
Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions
Human endogenous retroviruses (HERVs) are repetitive elements previously implicated in major psychiatric conditions, but their role in aetiology remains unclear.
Here, we perform specialised transcriptome-wide association studies that consider HERV expression quantified to precise genomic locations, using RNA sequencing and genetic data from 792 post-mortem brain samples.
In Europeans, we identify 1238 HERVs with expression regulated in cis , of which 26 represent expression signals associated with psychiatric disorders, with ten being conditionally independent from neighbouring expression signals.
Of these, five are additionally significant in fine-mapping analyses and thus are considered high confidence risk HERVs.
These include two HERV expression signatures specific to schizophrenia risk, one shared between schizophrenia and bipolar disorder, and one specific to major depressive disorder.
No robust signatures are identified for autism spectrum conditions or attention deficit hyperactivity disorder in Europeans, or for any psychiatric trait in other ancestries, although this is likely a result of relatively limited statistical power.
Ultimately, our study highlights extensive HERV expression and regulation in the adult cortex, including in association with psychiatric disorder risk, therefore providing a rationale for exploring neurological HERV expression in complex neuropsychiatric traits.
Zdroj: web
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Oldest known human viruses found hidden within Neanderthal bones
Genetic analysis of 50,000-year-old Neanderthal skeletons has uncovered
the remnants of three viruses related to modern human pathogens, and the
researchers think they could be recreated
Genetic sequences from three common viruses that plague humanity today have been isolated from the remains of Neanderthals who lived more than 50,000 years ago.
Marcelo Briones
at the Federal University of São Paulo, Brazil, says it may be possible
to synthesise these viruses and infect modern human cells with them in
the lab.
“These Jurassic Park -like viruses could then be studied for
their reproductive and pathogenic traits and compared to present-day
counterparts,” he says.
Briones and his colleagues analysed DNA from the skeletons of two male Neanderthals found in Chagyrskaya cave in Russia.
They identified the remnants of an adenovirus, which causes cold
symptoms in modern humans; herpesvirus, which can result in cold sores;
and the sexually transmitted papillomavirus, which can cause genital
warts and cancer.
They are the oldest human viruses ever discovered, superseding a 31,000-year-old virus found in Homo sapiens teeth recovered from north-east Siberia.
Briones says by comparing the genetic sequences with modern viruses,
the team has ruled out the possibility that the viruses came from
contemporary humans who may have handled the remains or predators that
may have fed on them.
“Taken together, our data indicate that these viruses might represent viruses that really infected Neanderthals,” he says.
Some researchers have speculated that viruses may have played a role in the Neanderthals’ extinction.
Briones says the team’s results add weight to the possibility, but
cannot confirm it. “To support their provocative and interesting
hypothesis, it would be necessary to prove that at least the genomes of
these viruses can be found in Neanderthal remains,” he says. “That is
what we did.”
The fact that a single Neanderthal could be infected with three
viruses isn’t surprising, he says, since humans today are infected by
about 10 different viral species, on average, during their lifespan.
Sally Wasef
at Queensland University of Technology in Australia says the study
suggests there is a high chance of further discoveries about past
diseases that may have affected anatomically modern humans and our
extinct human relatives.
However, the study of ancient viruses remains a new field that needs
more exploration, she says. “The current tools used to authenticate
ancient DNA results from humans might not apply to viruses, which have
shorter DNA strands by default.”
Briones’s goal of recreating the ancient viruses will be challenging,
she adds. “I am sceptical that this could be achieved given the lack of
full understanding of how the viruses’ DNA is damaged and how to
reconstruct the recovered pieces into a full viral genome. Also, the
host-virus interaction, especially in a completely different
environment, is something to consider.”
Zdroj: New Scientist
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Can genetically modifying a rare marsupial save it from extinction?
Researchers are aiming to make the northern quoll resistant to the toxic
cane toads wiping it out in Australia, but little progress has been
made
The US-based “de-extinction” company Colossal Biosciences claims a team it funds in Australia has taken “a major step” towards saving an endangered marsupial called the northern quoll.
The plan is to genetically modify the animals to make them resistant
to the toxin of the invasive cane toad, but so far the team has only
edited the cells of another marsupial.
The northern quoll (Dasyurus hallucatus ) is a small, mostly carnivorous marsupial found in northern regions of Australia. Very unusually for a mammal, the males die after mating .
Populations have been devastated by introduced predators such as cats and the loss of habitat. But the single biggest threat is the invasive cane toad (Rhinella marina ), which secretes a toxin that kills many would-be predators in Australia.
This works by inhibiting a protein that pumps sodium out of cells,
which means sodium levels can rise to dangerous levels. Outside of
Australia, small changes in the pump protein that confer resistance have evolved independently in a range of predators, from insects to hedgehogs.
Stephen Frankenberg
at the University of Melbourne, Australia, and his colleagues want to
edit the genome of the northern quoll to make it resistant too.
“Our toxin-resistance edit only changes a couple of DNA bases , which
would probably arise by natural spontaneous mutation eventually anyway
if quolls were to live with toads for the next few thousand years,” says
Frankenberg. “We’re just speeding up the process so they don’t go
extinct before resistance can evolve naturally.”
His team is far from the first to propose using genetic engineering
to help save endangered species. In the US, for instance, American
chestnut trees have been genetically modified to resist the fungus that wiped out most of them.
Engineering northern quolls could help save these animals, says Jonathan Webb at the University of Technology Sydney, Australia, who isn’t part of the team.
“If the genetically engineered quolls had sufficient toxin
resistance, then they would have a high chance of surviving a predatory
attack on a cane toad,” says Webb. “Thereafter, they’d either learn to
avoid toads, or they might exploit the toads as food, which could help
turn the tide on cane toads.”
Other approaches have failed, says Webb. For instance, his team tried to develop baits that would teach northern quolls to avoid cane toads , but this didn’t prove feasible on a large scale.
But not much progress has been made towards genetically modifying northern quolls. In 2020, Frankenberg told reporters
that the team had used CRISPR gene editing to introduce toxin
resistance into cells growing in a dish of another marsupial known as
the dunnart. It is in the same family as quolls, but is easier to work
with.
Now, the team is about to release a study showing that the edited
dunnart cells are 45 times more resistant to cane toad toxin than
unaltered ones.
Only one of the two copies of the sodium-pump gene has been altered,
the paper says. If both were altered, the resistance would be even
higher, it states.
“This is like someone climbing the first rung on a ladder and
proclaiming, ‘look, this first step proves I can reach the moon’,” says Merlin Crossley at the University of New South Wales in Sydney.
The thing is, the real challenge isn’t editing cells in a dish. To
genetically modify mammals, scientists must extract and manipulate egg
cells, and then implant embryos in receptive females.
This is easy to do in some well-studied animals such as mice, but
often fails when attempted in new species. Getting it to work can take a
lot of effort and a lot of individuals to practise on. That is costly
and especially difficult with endangered species.
What’s more, until 2021
no team in the world had managed to genetically engineer any marsupial.
A major issue is that their eggs develop a hard shell soon after
fertilisation that prevents the injection of things such as CRISPR gene
editing machinery.
Even if Frankenberg succeeds in engineering toxin-resistant quolls,
his team will still need to generate large enough numbers to release
into the wild to spread the resistance gene, not to mention getting
permission to release them.
“I like the idea and think it is worth exploring,” says Crossley. But the hard part is still to come, he says.
Zdroj: New Scientist
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CRISPR gene therapy improves vision in people with inherited blindness
A clinical trial called Brilliance, which included 14 participants,
showed that CRISPR gene editing led to improved vision in people with
inherited blindness. Mass Eye and Ear researchers said their findings
support further research into CRISPR therapies for inherited retinal
disorders. The results of 11 participants showed improvement in vision.
Also, they noted, this trial involved the first patient ever to
receive a CRISPR-based investigational drug directly into the body.
Principal investigator Eric Pierce pointed out
that the trial shows that gene therapy for hereditary vision loss is a
worthy pursuit for future research. He believes the early research is
promising.
“It’s a big deal to hear how thrilled they were to finally be able to
see food on their plates,” said Pierce. “These were individuals who
couldn’t read a single line on an eye chart. They had no treatment
options, which is an unfortunate reality for most people with inherited
retinal disorders.”
More about the participants, inherited vision loss, and the process
The goal is to inject CRISPR so that it reaches the retina to restore the ability to produce genes and proteins.
Participants received an injection of the CRISPR/Cas9 genome editing
drug, EDIT-101, into one eye through a specific surgical procedure. Of
the 14 participants, 12 were adults, meaning they were between the ages
of 17 and 63.
The remaining two were children aged 10 and 14. They were born with
Leber Congenital Amaurosis. It happens in a total of about 2 or 3 out of
100,000 newborns.
Leber Congenital Amaurosis is an eye disorder that affects the retina
and leads to severe visual impairment starting in childhood. According
to the data, different subtypes have been described, and they are caused
by genetic changes in different genes.
Thus, this rare disease can be caused by more than 200 different
genetic mutations. The CEP290 gene provides instructions for the
production of a protein involved in the structure and function of
cellular components. Therefore, mutations can lead to dysfunction and
can impair the ability of photoreceptor cells to respond to light.
11 life-changing results for inherited vision loss
For effectiveness, researchers looked at four criteria. That includes
best-corrected visual acuity; dark-adapted full-field stimulus testing,
navigation of visual functions, and vision-related quality of life.
In 2020, clinicians performed a BRILLIANCE clinical trial. That was
the first time that the first time CRISPR had been used to edit human
genes within the body.
Zdroj: Interesting Engineering
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Simulated space conditions disrupt 91% of human gene expressions
The study was motivated due to a surge in spaceflights with more and more astronauts undertaking expeditions to space. A new study aiming to understand the impact of simulated microgravity
on gene expression rhythms in humans revealed that this simulated
microgravity indeed disrupts gene expression in humans.
They found that when simulated microgravity is achieved through 60
days of consistent bed rest, it impacts the processing of information in
human genes that produce proteins and RNA molecules.
The study was motivated due to a surge in spaceflights with more and more astronauts undertaking expeditions to space.
Human gene expression in space condition
“This unique study represents the largest longitudinal dataset of
time series gene expression in humans,” stated lead author Simon Archer,
also professor of molecular biology of sleep at the University of
Surrey.
“Human gene expression varies rhythmically over the 24-hour day, and
it is important to collect time series data rather than from just single
time points to get a full picture of what occurs in the body when
exposed to simulated microgravity,” he added.
He additionally noted that exposure to such a stimulated environment
in space raised questions about the impact of constant bed rest on our
bodies as we have identified a dramatic effect on the temporal
organization of human gene expression .
Another study conducted by the European Space Agency noted that when
20 men went through a 90-day protocol consisting of two weeks of
baseline before 60 days of constant bed rest at a -six-degree head-down
tilt angle to simulate the effects of microgravity experienced by
astronauts according to a statement by the researchers. This protocol was completed with two weeks of recovery.
Disruptions affecting 91% of genes
The study conducted by the University of Surrey evaluated gene
expression patterns in 24 hours at different phases of the study
including baseline, bed rest, and recovery of the astronauts.
The team discovered 91 percent of these gene expressions to be
impacted by the protocol with significant disruptions to the rhythmic
patterns. This further affects the biological processing of the human
body from protein translation, immune response, and inflammation to
muscle function.
While recovery, the aspects of the interrupted muscle function were
restored, implying a partial recovery but subjects still experienced
lasting consequences in protein translation.
This indicated that simulated microgravity’s influenced gene
expression continued to persist in the participants even after they
returned to normal conditions.
“Space travel was once thought to be unachievable; however, the
growth of the space industry means it is now a real possibility,”
expressed Senior author Derk-Jan Dijk, professor of sleep and physiology
and director of the Surrey Sleep Research Centre.
“A lot remains unknown about the impact of microgravity on the body,
and it is important we know more about this before we start ‘holidaying’
in space. Building on what we have found, the second part of our study,
using the same cohort of men, will investigate the impact microgravity
has on sleep, circadian rhythms, and hormones of individuals.”
This study was published in the journal– iScience on March 15, 2024.
Study Abstract
Physiological and molecular processes including the
transcriptome change across the 24-h day, driven by molecular circadian
clocks and behavioral and systemic factors. It is not known how the
temporal organization of the human transcriptome responds to a
long-lasting challenge. This may, however, provide insights into
adaptation, disease, and recovery.
We investigated the human 24-h time series
transcriptome in 20 individuals during a 90-day constant bed rest
protocol. We show that the protocol affected 91% of the transcriptome
with 76% of the transcriptome still affected after 10 days of recovery.
Dimensionality-reduction approaches revealed that many affected
transcripts were associated with mRNA translation and immune function.
The number, amplitude, and phase of rhythmic transcripts, including
clock genes, varied significantly across the challenge.
These findings of long-lasting changes in the
temporal organization of the transcriptome have implications for
understanding the mechanisms underlying health consequences of
conditions such as microgravity and bed rest.
Zdroj: Interesting Engineering
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Mental health conditions may accelerate ageing by damaging RNA
People with a mental health condition have more RNA damage than those without one. Since RNA damage is known to accelerate ageing, these findings could explain why mental health conditions are linked to an increased risk of dying from age-related diseases such as cancer or type 2 diabetes. Anders Jørgensen at the Psychiatric Center Copenhagen in Denmark and his colleagues measured markers of damaged RNA and DNA in more than 7700 people ages 25 and up, almost 3100 of whom had a mental health condition. They focused on markers of oxidative stress, which occurs when highly reactive compounds containing oxygen damage cells. Oxidative stress contributes to age-related diseases like heart disease, dementia and cancer . Sources of the compounds that cause oxidative stress include digestion, smoking and pollution.
The researchers analysed levels of oxidative stress markers in urine samples collected from participants between 2007 and 2013. After taking into account the age and sex of the participants, they found that samples collected from people with a mental health condition had elevated amounts of a particular marker of RNA damage. Levels of the marker were 9 per cent higher, on average, in these samples than in samples from people without a mental health condition.
By tracking participant deaths from the time each of them joined the study until the end of May 2023, the team discovered that those with elevated levels of the marker were also more likely to die during this time. Participants with high levels of the marker and a mental health condition were almost twice as likely to die as those with low levels and no mental health condition.
Together, these findings suggest that RNA damage from oxidative stress may explain the association between mental health conditions and premature death.
Why people with psychiatric conditions experience more oxidative stress is unclear, though, says Jørgensen. “We can only guess. But overall, the level of factors that could cause oxidative stress – like smoking or obesity – are usually higher in people with psychiatric illness,” he says. The study didn’t control for these aspects of health, so they might help explain the increases in oxidative stress.
Identifying exactly which of these factors have the biggest effect will be critical for improving the health of people with mental health conditions, says Jasmin Wertz at the University of Edinburgh in the UK. “So, how much impact can we have by helping [them] reduce their smoking? Getting them to exercise more?” she says.
Zdroj: New Scientist
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Colorado’s Star DNA Analyst Intentionally Manipulated Data, Investigation Finds
Yvonne “Missy” Woods allegedly cut corners and violated policies for years, affecting more than 650 cases Colorado’s star DNA scientist intentionally manipulated evidence for years, calling into question all of the criminal cases she worked on in her nearly three-decade career, according to a preliminary investigation released by officials Friday. Yvonne “Missy” Woods, who helped solve some of the state’s most notorious crimes, abruptly left her post last November after the Colorado Bureau of Investigation discovered anomalies in her work and initiated a criminal probe. The internal inquiry released Friday asserts that Woods, long one of the bureau’s most respected analysts, purposefully altered DNA testing results. The report said her manipulation affected at least 652 cases she handled between 2008 and 2023. The total could end up being higher, as investigators are still reviewing Woods’s cases dating back to the beginning of her career in 1994. “Our actions in rectifying this unprecedented breach of trust will be thorough and transparent,” said CBI Director Chris Schaefer. The review didn’t find that Woods falsified DNA matches or fabricated DNA profiles. Instead, it said she omitted material facts in records, tampered with DNA testing results, and violated a variety of lab policies including quality-control measures. State officials previously said they would need to retest and review a total of about 3,000 DNA samples handled by Woods. Her lawyer, Ryan Brackley, said Woods never created or falsely reported any exculpatory DNA evidence or gave false testimony resulting in someone being wrongfully convicted or imprisoned. “To the extent that the findings of the internal investigation will call her good work into question, Ms. Woods will continue to cooperate to preserve the integrity of her work,” he said. For months, Colorado’s criminal justice system has been in disarray at the revelations that DNA analysis conducted by Woods, who worked on such notable cases as the “Colorado Hammer Killer,” may not have been conducted properly. Prosecutors are already reviewing hundreds of cases that Woods handled and scrambling to figure out how to deal with coming trials where she provided DNA analysis. Defense lawyers have been in touch with clients who were convicted based on Woods’s findings and now want to file appeals. State lawmakers recently allocated $7.5 million to help pay for retesting and potential retrials. “For the past several months, prosecutors around the state have waited anxiously for information because of the impact on victims, the accused, and our ability to do justice,” said Boulder County’s District Attorney Michael Dougherty. Mary Claire Mulligan, an attorney whose client faces a triple murder trial in April for a case in which Woods provided DNA testing that investigators have found was incomplete, said officials need to determine how Woods’s manipulations went on for so long. “We need nothing less than complete transparency from CBI and the attorney general’s office about how this deliberate and pervasive fraud evaded detection,” she said. Experts say the scandal could potentially be one of the largest in the history of forensic DNA testing. The CBI said it is working on changes to bolster the integrity of its DNA testing program. The criminal investigation into Woods, which is being handled by South Dakota’s Division of Criminal Investigation on Colorado’s behalf to avoid a conflict of interest, is continuing.
Zdroj: web
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Puzzling skin side effects stymie advance of promising HIV vaccine
Strategy of multiple, Moderna-made mRNA shots to hone powerful antibodies hits a pothole One of the most promising attempts to reinvigorate the stalled quest
for an HIV vaccine has hit a snag that might seem minor but has major
consequences: delaying the larger trials needed to show whether the
concept works. In small safety and immune tests of the innovative
vaccine strategy, which relies on a series of messenger RNA (mRNA)
shots, an unusually high percentage of recipients developed rashes,
welts, or other skin irritations.
“We are taking this very seriously,” says Carl Dieffenbach, who heads
the Division of AIDS at the National Institute of Allergy and
Infectious Diseases, which funded a recent phase 1 trial of the vaccine.
Researchers want to understand the cause of the skin problems and how
to minimize them before expanding tests of the vaccines, which are made
by Moderna. “We would be moving more quickly if this finding had not
been observed,” says Mark Feinberg, who heads IAVI , a nonprofit that is the vaccine’s major sponsor.
The complex vaccine strategy involves injections of different mRNAs,
encoding various pieces of HIV’s surface protein or the entire molecule,
over the course of several months. The goal is to gradually guide the
immune system’s B cells to produce so-called broadly neutralizing
antibodies, or bnAbs, capable of stopping many different variants of the AIDS virus .
People living with HIV on rare occasions eventually produce bnAbs, but
no vaccine has ever done so—which has become the “holy grail” for the
field, says Linda-Gail Bekker, an AIDS vaccine researcher in South
Africa who runs the Desmond Tutu HIV Centre at the University of Cape
Town.
Different versions of this HIV vaccine have already gone through
three phase 1 trials, but they totaled fewer than 200 participants. The
recipients responded with impressive antibodies that were moving toward
bnAbs, fueling hopes for the vaccines. But skin problems—including
urticaria (hives), pruritus (itching), and dermatographism (welts after
scratching)—occurred at a noticeably high level in all of the studies, affecting 11 out 60 people in one of them .
These HIV vaccines deliver a relatively high dose of mRNA, which
Moderna scientists and others think could explain the skin issues. The
company’s original COVID-19 mRNA vaccine used the same dose and has also
been linked to skin problems, although at much lower frequencies, of 1%
to 3%. (The Pfizer-BioNTech collaboration’s COVID-19 vaccine, also
based on mRNA but given at a 70% lower dose, triggers skin problems,
too, but one Swiss study suggests they occur 20 times less frequently than with the Moderna product .)
Potentially more worrisome, however, would be if the problem is tied to
a cumulative effect from multiple mRNA shots or the genetic background
of the recipients, or if the HIV sequence itself were responsible for
the welts and hives.
Most of these skin problems quickly resolved and weren't severe
enough to stop any trial, but researchers do not want to minimize them.
“At a time when vaccine hesitancy is high, it is critically important
not to dismiss urticaria as an unimportant side effect,” says Kimberly
Blumenthal, an allergist at Massachusetts General Hospital who has also
found a link between Moderna’s COVID-19 vaccine and higher rates of urticaria .
Feinberg agrees the side effect issue needs studying, but is also
concerned that people who are vaccine opponents might misrepresent the
scope of the problem. “This finding has not been seen to the same
frequency with other mRNA vaccines against other pathogens,” he says.
Had the problem in the HIV trials not surfaced, the researchers would
have moved closer to conducting—or even launched—a study that involved a
few hundred people and had a placebo control. If the results were
positive, a phase 3 efficacy trial would determine whether it was safe,
worked, and should come to market. “We’ve hit this rather miserable bump
in the road,” Bekker says.
Multiple research groups are pursuing similar strategies to create
bnAbs. Moderna’s effort grew out of a project led by biophysicist
William Schief, who developed it at Scripps Research and then brought
the strategy to the company, where he is now a vice president. It
exploits the fact that B cells begin as naïve, or germline, cells and
then during an infection undergo a series of mutations that, in effect,
hone the ability of the antibodies they produce to bind to specific
parts of viruses and “neutralize” their ability to infect cells. The
“germline targeting” vaccine strategy relies on several shots to take B cells through this maturation process , eventually leading them to produce bnAbs against viruses.
“We call it priming, shepherding, and polishing,” explains Dennis
Burton, an immunologist at Scripps who works with Schief. Initially the
group did not use mRNA. Its vaccine contained a small piece of HIV’s
viral surface protein attached to a nanoparticle that presented it to
the immune system in a novel way, and early results were promising. In a
2022 Science paper, Schief and colleagues reported that 97% of the 36 people who received the vaccine developed the B cell antibody gene mutations needed to progress toward becoming broadly neutralizing.
Schief switched to mRNA because it provides far more flexibility,
allowing the researchers to readily fine-tune the HIV component of the
vaccine. Because of the enormous diversity of HIVs in circulation, he
contends that an effective vaccine likely will have to trigger
production of up to five different bnAbs. That would mean priming,
shepherding, and polishing multiple B cell lineages. Without the
easy-to-modify mRNA, Schief says, “good luck—that is a daunting,
daunting task.”
NIAID now plans to repeat the phase 1 trials of some of these Moderna/IAVI HIV vaccines with a lower dose.
Bekker, who lives in a country that has more people living with HIV
than any other, is still hopeful the approach will pan out. “We’ve got
to chapter one of an exciting novel.” After decades of failed attempts
to develop an HIV vaccine, the goal remains pressing, she says. “Last
year, the world had 1.3 million infections of HIV. I think it remains an
urgent requirement to find a good solution.”
Zdroj: web
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Crucial chemical for life can form in conditions found on early Earth
Pantetheine, which helps enzymes to work and is found in every organism,
can be formed by simple reactions and may have played a role in the
origins of life
One of the most important molecules in living organisms has been
synthesised from scratch under everyday conditions. The finding suggests
that the chemical could have formed naturally early in our planet’s
history and played a role in the origins of life.
The substance in question is called pantetheine. It isn’t a household
name on the level of DNA or protein. However, pantetheine is the key
component of a larger molecule called acetyl coenzyme A, a “cofactor” that helps enzymes to work.
“Coenzyme A is in every organism ever sequenced,” says Matthew Powner at University College London.
Powner has spent most of his career finding ways to make biological
molecules from simple chemicals in ways that could have occurred
naturally. In the past decade, he has shown that simple aminonitriles can be used to make nucleotides – the building blocks of DNA – and peptides, short versions of proteins.
His team has now shown that aminonitriles can be used to make
pantetheine in a series of reactions starting with simple chemicals like
formaldehyde. This took place in water, often at concentrations so
dilute that the reaction mixtures looked like clear water. Sometimes the
team used heat to speed things up, but otherwise didn’t need to
intervene once the reactions were under way.
“It’s just all one pot – literally just throw it all in, don’t change
anything, don’t do anything – and we get 60 per cent yield of our
product,” says Powner.
Acetyl coenzyme A is involved in the synthesis of several
biologically crucial chemicals. Some of the oldest groups of
microorganisms use processes involving it to obtain carbon from the
environment.
Crucially, pantetheine is the active part of the acetyl coenzyme A
molecule. The other bit “isn’t essential to its function”, says Powner.
Cofactors of this sort are found in all living organisms. They have been described as remnants of life’s origin and early evolution .
“Obtaining any key organic biological cofactor from scratch” would be
impressive, “let alone one of such central importance”, says Zachary Adam at the University of Wisconsin-Madison, who wasn’t involved in the research.
For Adam, the significance of the study goes beyond pantetheine and
acetyl coenzyme A. “They are reporting this particular part of the
cofactor, but the intermediates are being shown to be just as
important,” he says. Other chemicals produced along the way have been
shown to help make other biological molecules. “They’re building out
this network of compounds.”
Many ideas about the origins of life have assumed that a small set of
biological molecules formed long before the others. For instance, the
“RNA world” hypothesis states that the first life was made solely of
RNA, with other chemicals like proteins and lipids being added later
once the RNA was capable of making them.
Powner is one of several researchers pushing for a different scenario ,
in which many key molecules formed early and interacted from the
beginning. “All of these products can be a product of the same chemical
reactions,” he says. Rather than starting with just RNA or just
peptides, “it could be easier to make all of them together, and then the
chemistries that they do are integrated from the origin”.
Zdroj: New Scientist
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DNA samples reveal cases of Down Syndrome in prehistoric humans
Ancient DNA analysis has opened a window
into the past, revealing instances of Down Syndrome in historical
populations from Bronze and Iron Ages.
This genetic disorder affects around one in every 1,000 newborns today.
Researchers at the Max Planck Institute for Evolutionary Anthropology explored the ancient past's genetic conditions.
They
have gathered ancient human DNA dating back tens of thousands of years.
The scientists examined more than 10,000 DNA samples in this new
study.
They were able to identify six people who all had an extra copy of Chromosome 21, which is an indication of Down Syndrome.
All six individuals died at a very young age These instances span diverse historical periods.
One instance, uncovered in a Finnish church graveyard, can be traced back to the 17th to 18th century.
The remaining five people, dating back 5,000 to 2,500 years, were discovered at Bronze Age sites in Greece and Bulgaria and Iron Age sites in Spain.
These prehistoric individuals with Down Syndrome faced challenging times, with all six succumbing to an early fate, most never reaching the age of one.
The
absence of treatment most certainly led to their early death.
Individuals with Down Syndrome can now live longer lives, thanks to the
advancements in modern medicine.
They were laid to rest carefully,
surrounded by colored bead necklaces, bronze rings, and sea shells –
tokens of appreciation from their ancient societies. The five burials
were found to be located within settlements.
One ancient case of rare Edwards Syndrome identified But the
research doesn't end there. Amidst the quest for Down Syndrome cases,
the researchers stumbled upon another enigma – an individual from the
Spanish Iron Age with an unexpected genetic anomaly.
This
individual carried three copies of Chromosome 18, a rare condition known
as Edwards Syndrome, with far more severe health implications than Down
Syndrome.
Edwards Syndrome occurs in fewer than one case per 3,000 births.
“At
the moment, we cannot say why we find so many cases at these sites
[Spanish Iron Age],” said Roberto Risch, an archaeologist of the
Universitat Autònoma de Barcelona, who works on intramural funerary
rites.
Risch further added: “But we know that they belonged to the
few children who received the privilege to be buried inside the houses
after death. This already is a hint that they were perceived as special
babies.”
The team highlights that these revelations are just the
beginning. With the number of DNA samples growing, the researchers
strive to unveil how ancient societies cared for those who needed a
helping hand or were slightly different.
“What we would like to
learn is how ancient societies reacted to individuals that may have
needed a helping hand or were simply a bit different,” said Kay Prüfer,
who coordinated the DNA sequence analysis, in the press release .
Zdroj: Interesting Engineering
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Inhalable therapy shows promise in treating lung cancer
Cancer, especially lung cancer, is still incredibly tough to beat. Despite recent advancements in its treatment, lung cancer remains complicated. It doesn't always respond well to medications.
However, Columbia University researchers offer a potential solution: inhalable IL-12 mRNA therapy .
What is IL-12 mRNA? IL-12
is a vital molecule in the immune system. It acts as a messenger,
specifically targeting T cells (immune system soldiers) and guiding them
to be more effective against threats like cancer and infections.
The
instructions for creating IL-12 are contained within a molecule called
IL-12 mRNA. Scientists are investigating how to deliver this message to
cells directly. This will enable them to produce their IL-12 and
activate the immune system in a targeted way.
Using IL-12 mRNA this approach could lead to new cancer treatment options.
Promising new approach Researchers wrapped mRNA in tiny natural carriers named extracellular vesicles (EVs) for targeted delivery.
These EVs were isolated from human kidney cells and loaded with the mRNA using a mild electrical pulse.
To
test their approach, they injected mice with lung cancer cells. Later,
they delivered the mRNA-loaded EVs through a nebulizer, aiming them
directly at the lungs.
The researchers tracked where the EVs went in the body and how they affected the tumor's immune response.
The lab investigated how well the EVs penetrated mucus and entered cancer cells and immune cells called macrophages.
Inhaling a breath of hope The
study found that breathing in tiny natural carriers loaded with
instructions for making an immune molecule (IL-12 mRNA) was highly
effective in treating lung cancer in mice.
Using "extracellular
vesicles" (EVs), this method worked better than traditional delivery
methods and led to smaller tumors, longer survival, and stronger immune
responses.
The therapy triggered a powerful immune attack on the
tumors, including increased production of a key immune molecule (IFNγ)
and more potent killer cells (CD8+ T cells and NK cells).
Inhaling a breath of hope: Researchers wrapped mRNA in tiny natural carriers named extracellular vesicles
(EVs) for targeted delivery. These EVs were isolated from human kidney
cells and loaded with the mRNA using a mild electrical pulse. To test
their approach, they injected mice with lung cancer cells. Later, they
delivered the mRNA-loaded EVs through a nebulizer, aiming them directly
at the lungs. The researchers tracked where the EVs went in the body and
how they affected the tumor's immune response. The lab investigated how
well the EVs penetrated mucus and entered cancer cells and immune cells
called macrophages.
Their analysis
also showed that specific immune cells (CD8+ T cells) were crucial for
the therapy's success, highlighting their role in fighting cancer and
building immunity.
Conclusion The study suggests a breakthrough in treating lung cancer.
Professor
Ke Cheng, the lead researcher, highlighted, "In this new study, we show
that inhaled exosomes can efficiently reach the lung and deliver an anti-lung cancer
cargo, IL-12 mRNA. This is a major step forward in advancing the
development of new inhalable drugs to treat lung cancer, which has one
of the lowest five-year survival rates in the world."
This targeted approach avoided harming healthy tissue and boosted the immune system's attack on the cancer.
This
method could lead to safer, more effective treatments for lung cancer,
with easier administration and longer-lasting benefits.
While additional human studies are necessary, the findings reveal promising potential for transforming cancer treatment.
Zdroj: Interesting Engineering
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Study finds penile fibroblasts are a key player in erectile function
Learn how fibroblasts play a crucial role in fine-tuning blood flow, potentially reshaping the way we approach erectile dysfunction treatments. A new study published in Science on February 8 might change our approach toward treating erectile dysfunction. Researchers have uncovered a key player in the intricate dance of penile blood flow regulation in mice. The findings shed light on the role of fibroblasts in the erectile process, opening doors to potential therapeutic alternatives for human erectile dysfunction. For men, the ability to achieve and maintain penile erections is crucial for sexual health and overall well-being. However, various factors, including aging, diabetes, and atherosclerosis, can compromise this function. The study, led by Eduardo Linck Guimaraes and his team, focused on understanding the role of fibroblasts in the physiology of erections. "Fibroblasts are the most abundant cells in the penis of both mice and humans, but they have been neglected in research," said Eduardo Guimaraes in a press statement. "Now we can show, using a very precise method called optogenetics, that they have a very important role in regulating blood flow in the penis, which is what makes the penis erect." The corpora cavernosa (CC) is erectile vascular tissue responsible for blood flow and enlargement during vasodilation. It plays a pivotal role in penile erection. The sympathetic release of norepinephrine can suppress penile blood flow, while nitric oxide and acetylcholine, released during sexual arousal, counteract this effect, leading to vasodilation within the CC. Despite our knowledge of these mechanisms, the regulation of this intricate system has remained elusive. The researchers identified two significant populations of previously unknown perivascular fibroblast cells within the CC by employing single-cell RNA sequencing, optical tissue clearing, and optogenetic activation techniques in a transgenic mouse model. Number of fibroblasts fine-tune blood flow regulation These fibroblasts express the norepinephrine transporter SLC1A3, and their role was found to mediate vasodilation by reducing norepinephrine availability. The study also revealed a newly found aspect of fibroblast behavior. The number of fibroblasts in the CC was found to fine-tune blood flow regulation. An increased frequency of erections stimulated fibroblast proliferation, which was achieved by down-regulating Notch signaling. This process resulted in a higher number of fibroblasts, elevated basal penile blood flow, and reduced sensitivity to norepinephrine. Ji-Kan Ryu and Gou Young Koh, writing in a related Perspective, emphasized the potential implications of the study for human health. While the study was conducted in mice, the authors propose a new therapeutic paradigm that involves creating conditions to increase norepinephrine uptake or decrease Notch signaling in penile perivascular fibroblasts. This approach holds promise for treating erectile dysfunction in patients unresponsive to current therapies. The findings point toward a dynamic coordinating role of Notch signaling in CC fibroblasts during the erectile process. Although the study did not directly examine humans, the implications for future therapeutic interventions are significant. The prospect of manipulating fibroblasts to enhance vasodilation opens up a new frontier in the quest to address erectile dysfunction, potentially offering hope for individuals facing challenges with existing treatments.
Zdroj: Interesting Engineering
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Vaccine for deadly skin cancer shows ‘groundbreaking’ results in clinical trial
New hope may be on the horizon for melanoma patients in the form of a novel skin cancer vaccine.
This week, Moderna announced that its new vaccine has shown promising results in clinical trials.
Among 157 patients with advanced melanoma ,
the vaccine led to "statistically significant improvement in survival
before the cancer returned," according to a statement from Hackensack
Meridian John Theurer Cancer Center in New Jersey, which has been
participating in the clinical trials.
In the study, the vaccine was used in combination with Merck’s immunotherapy drug, Keytruda.
"Keytruda
is a checkpoint inhibitor, meaning it blocks an enzyme that the cancer
cell uses to become invisible to the immune system," said Dr. Marc
Siegel, clinical professor of medicine at NYU Langone Medical Center and a Fox News medical contributor, was not involved in the vaccine trials.
In clinical trials, Moderna's melanoma vaccine was used in combination with Merck’s immunotherapy drug, Keytruda. (iStock)
"Keytruda
works well in certain kinds of highly mutagenic cancers, including
melanoma, and there is often a very effective response," Siegel told Fox
News Digital.
"But the cancer can then mutate away from the impact of the drug and once again become resistant to an immune response."
Fox News medical contributor Dr. Marc Siegel said that Moderna's mRNA vaccine "shows real promise." (Fox News)
The
patients who took the experimental mRNA vaccine along with Keytruda —
all of whom previously had surgery to remove their cancer — saw a 44%
reduction in the risk of death or recurring disease compared to those
who did not take the vaccine, the companies said.
"This is truly
game-changing, groundbreaking stuff," said Dr. Andrew Pecora, an
oncologist and researcher at the Hackensack Meridian John Theurer Cancer
Center, who has been involved in the clinical trials since they began.
"This is truly game-changing, groundbreaking stuff,"
said Dr. Andrew Pecora, an oncologist and researcher at the Hackensack
Meridian John Theurer Cancer Center, who has been involved in the
clinical trials since they began. (Hackensack Meridian)
Immunotherapy
has been shown to be effective in about half of cancer patients, Pecora
noted — but for the other half, the proteins of the tumor are not
properly presented to the immune system to be recognized and killed.
"In
those cases, the melanoma is kind of hiding out or it doesn't express
proteins that well, so the immune system doesn't recognize the proteins
as foreign," Pecora told Fox News Digital in a phone interview.
The Moderna vaccine is "revolutionizing" the immune system’s ability to recognize and kill the melanoma, he said.
The vaccine, which Pecora described as "miraculous," is personalized to each patient’s specific tumor.
"You
and I may have melanoma, but my melanoma may be very different than
yours even though it looks exactly the same under the microscope,
because the DNA changes that occurred in mine are different than yours,"
he told Fox News Digital.
That means a generic cancer vaccine wouldn’t work for everyone, Pecora said.
With the new vaccine, the scientist takes a piece of the person's
tumor and precisely determines what parts of the DNA of the tumor are
mutated or changed, and then creates a personalized mRNA vaccine that
targets those changed pieces of DNA, the doctor said.
"We can
literally vaccinate the person against their tumor-specific proteins,
overcoming one of the limitations of current immunotherapy," he said.
"The simultaneous use of an mRNA vaccine seems to show improved regression and remission of metastatic melanoma," Siegel said.
"I think this shows real promise for combined therapies."
The vaccine is now entering Phase 3 trials , as the researchers work to determine how and when it will receive FDA approval.
The trial participants have not reported any side effects other than what they experienced with immunotherapy, Pecora said.
"It could be approved as soon as the next year or two," he predicted.
The hope is that this breakthrough will also be applied to other forms of cancer beyond melanoma.
The deadliest form of skin cancer, melanoma is fast-growing and can spread to any organ.
In 2023, nearly 187,000 Americans were expected to be diagnosed with melanoma, according to the Melanoma Research Foundation.
More
than 97,600 of those will be diagnosed with invasive melanoma, and
7,990 Americans are expected to die from the disease in 2023.
Zdroj: web
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Breakthrough: Artificial DNA opens door to designer proteins
DNA, the molecule
that stores the genetic information of all living things, is made up of
just four chemical letters, or nucleotides. But what if we could add
more letters to this alphabet and create new kinds of DNA?
That's
what a team of researchers from the University of California San Diego,
the Foundation for Applied Molecular Evolution, and the Salk Institute
for Biological Studies have done. They have developed a new version of DNA with six letters instead of four, showing that it can be used to make proteins, the building blocks of life.
This feat, published in Nature Communications , opens doors to a future where custom-designed proteins and novel biological applications could become a reality.
Four nucleotides DNA,
the blueprint of life, encodes its instructions using just four
nucleotides – adenine (A), thymine (T), guanine (G), and cytosine (C).
These nucleotides pair in specific configurations, forming the iconic
double helix. But what if this alphabet could be expanded? The
implications are compelling, ranging from personalized medicine to
revolutionary materials.
"Life on Earth is amazingly diverse with
just four nucleotides, so imagine what we could do with more," said Dong
Wang, Ph.D., a professor at Skaggs School of Pharmacy and
Pharmaceutical Sciences at UC San Diego and the senior author of the
study.
"By expanding the genetic code, we could create new
molecules that have never been seen before and explore new ways of
making proteins as therapeutics."
Wang and his
colleagues used a synthetic DNA system called AEGIS, which stands for
Artificially Expanded Genetic Information System. AEGIS was created by
Steven A. Benner, PhD, at the Foundation for Applied Molecular
Evolution, as part of a NASA-funded project investigating how life could
have evolved in other planets.
Dr. Dong Wang aptly describes that
adding new 'letters' to the genetic code expands the vocabulary of
life, allowing us to write more complex narratives." His team's
breakthrough demonstrates that cells can readily incorporate synthetic
nucleotides into the DNA recipe.
Using AEGIS AEGIS adds
two new letters to the standard DNA alphabet, which consists of adenine
(A), thymine (T), guanine (G), and cytosine. These letters pair up in a
specific way to form the double-helix structure of DNA, which was
discovered by James Watson and Francis Crick in 1953.
The new
letters, Z and P, have the same shape and size as the natural ones, so
they can fit into the DNA helix without disrupting its geometry. This
means that the enzymes that read and copy DNA, such as RNA polymerase,
can recognize and process AEGIS DNA just like natural DNA.
RNA polymerase The
key lies in mimicking nature's machinery. The researchers identified
RNA polymerase, a key enzyme that converts DNA into RNA, which is then
used to make proteins. They designed two artificial nucleotides that
flawlessly mimic the geometry of natural nucleotides. RNA polymerase
readily accepted these novel additions when tested, seamlessly
incorporating them into transcription.
The researchers tested
whether RNA polymerase from bacteria could transcribe AEGIS DNA into RNA
and found that it could do so with high accuracy and efficiency.
"This is a remarkable demonstration
of how robust and adaptable the biological machinery is," said Wang.
"By mimicking the natural shape of DNA, our synthetic letters can sneak
in and be used to make new proteins."
This breakthrough
paves the way for exciting possibilities. Imagine designing proteins
with tailor-made properties capable of precisely targeting tumors for
cancer therapy or engineering bacteria to synthesize eco-friendly
biofuels. The vast horizons extend beyond medicine and environmental
applications to materials science and potentially even synthetic
biology.
Of course, challenges remain. Optimizing the
incorporation of new nucleotides, ensuring their stability within the
genome, and deciphering the full potential of this expanded code are
areas for further exploration. Yet, the foundation for rewriting the
genetic lexicon has been laid.
This discovery signifies a
momentous leap in our understanding of life's blueprint. It holds the
promise of ushering in a new era of biological design, where the
possibilities are limited only by our imagination.
"These new
proteins could have applications in medicine, biotechnology, and
bioengineering," said Wang. "We are only scratching the surface of what
we can do with artificial DNA."
Study abstract: Artificially
Expanded Genetic Information Systems (AEGIS) add independently
replicable unnatural nucleotide pairs to the natural G:C and A:T/U pairs
found in native DNA, joining the unnatural pairs through alternative
modes of hydrogen bonding. Whether and how AEGIS pairs are recognized
and processed by multi-subunit cellular RNA polymerases (RNAPs) remains
unknown. Here, we show that E. coli RNAP selectively recognizes
unnatural nucleobases in a six-letter expanded genetic system.
High-resolution cryo-EM structures of three RNAP elongation complexes
containing template-substrate UBPs reveal the shared principles behind
the recognition of AEGIS and natural base pairs. In these structures,
RNAPs are captured in an active state, poised to perform the chemistry
step. At this point, the unnatural base pair adopts a Watson-Crick
geometry, and the trigger loop is folded into an active conformation,
indicating that the mechanistic principles underlying recognition and
incorporation of natural base pairs also apply to AEGIS unnatural base
pairs. These data validate the design philosophy of AEGIS unnatural
basepairs. Further, we provide structural evidence supporting a
long-standing hypothesis that pair mismatch during transcription occurs
via tautomerization. Together, our work highlights the importance of
Watson-Crick complementarity underlying the design principles of AEGIS
base pair recognition.
Zdroj: Interesting Engineering
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Rare gene variants can change your height by up to 7 centimetres
Gene variants that have an unusally large effect on some people's
heights have been discovered by analysing the genomes of more than
300,000 individuals
Nearly 30 rare gene variants that decrease people’s height by up to 7
centimetres, or raise it by up to 5 cm, have been discovered by
analysing the genomes of more than 300,000 individuals.
“The variants I found, they’re very rare, so less than 1 per cent of
individuals carry them, but their effects are very large,” says Gareth Hawkes at the University of Exeter Medical School in the UK.
Height is largely genetically determined, with environmental factors
such as nutrition playing only a minor role. By comparing the gene
variants in millions of people with their heights, more than 12,000 common gene variants that are linked with stature have already been identified .
However, these common variants usually only have a small effect, typically raising or lowering height by a millimetre or less.
Common variants have mainly been found by analysing data from
so-called DNA chips, which look at sites in the genome where single DNA
letters often vary between individuals. Such studies cannot identify rare variants that are not included in the DNA chips.
Now, the number of whole-genome sequences is becoming large enough to
identify rare variants that affect height. Hawkes and his colleagues
started by analysing the genomes of 200,000 people in the UK Biobank
study. They then checked the findings by looking at another 130,000
genomes from two US projects called All of Us and TOPMed. This means
their research is based largely on people with European ancestry.
The team found 29 rare variants that have an average effect of about 3
cm, but can add up to 5 cm to someone’s height or take off 7 cm. Most
appear to act by altering the level of activity of genes, rather than
altering the proteins encoded by genes.
Loic Yengo
at the University of Queensland in Australia, who carried out the study
that identified 12,000 common variants, says the variants found so far
in people of European ancestry explain only about half of the variation
that is thought to be genetic.
“This work is complementary to ours,” says Yengo. “However, the 29
variants identified in this study account for a very limited amount of
height variance. So there is still a long way to go before we identify
all the rare variants responsible for the missing heritability.”
Tallness is regarded as a desirable attribute in many cultures, so much so that some people pay large sums for leg-lengthening operations that involve breaking both femurs. However, last year Sridharan Raghavan at the University of Colorado reported that certain gene variants linked to greater height also increase the risk of some nerve, skin and heart conditions .
“The mechanism linking height with cardiovascular traits still needs
some elucidation, so any relationship of newly discovered
height-associated rare variants with cardiovascular traits would likely
have to be tested directly,” says Raghavan.
However, some conditions such as varicose veins are probably
associated with height at least partially for physical reasons, he says,
such as the return of blood from the feet being more physically
demanding.
Hawkes says he does not see any immediate medical applications for the latest findings. However, understanding the genetics
of height will help us understand the genetics of other traits, too.
“Our predictions, not just for height but for disease and all kinds of
[traits], are going to get better and better,” he says.
In theory, in vitro fertilisation (IVF) clinics could screen embryos
for these variants and give parents a choice of having taller children, as at least one IVF clinic does with eye colour .
The idea of parents choosing their children’s traits is controversial
and in the case of the latest research, only a few per cent of people
possess any of these rare variants.
Zdroj: New Scientist
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Mutation behind Huntington's linked to higher childhood intelligence
The genetic mutation that causes the brain condition Huntington's
disease may result in greater intelligence among young people, which
could mean evolution selected for it
The genetic mutation that causes Huntington’s disease, a devastating
brain condition, may have been selected for by evolution because it also
leads to higher intelligence in people’s childhood and 20s.
This idea may not only lead to a rethink of strategies to treat
Huntington’s, but could also change our perspective on the genetics of
intelligence. “There are a lot of implications for our understanding of
the biology of the brain,” says Jordan Schultz at the University of Iowa, one of the authors of an analysis outlining the latest idea.
Huntington’s is a rare genetic condition that usually strikes in
middle age, beginning with unusual jerking movements and cognitive
problems before progressing inexorably to death. The condition is
especially cruel because those affected often witness a parent becoming
increasingly disabled, knowing they have a 50-50 chance of the same
fate. A genetic test is available, but many refuse it as there are no
effective treatments.
The mutation responsible for Huntington’s affects a gene called huntingtin ,
which encodes a protein made in the brain. The longer, mutated form of
the gene may have from 40 to more than 100 repeats of the same three DNA
“letters”, but even in the standard version of the gene, there are
usually between nine and 35 of these triplet repeats.
It isn’t yet known exactly how the longer form of the gene causes
Huntington’s symptoms. The leading idea is that the mutated protein is
somehow toxic to neurons, mainly based on post-mortem studies looking at
the brain cells of those affected.
Recently, though, an alternative idea has been gaining ground. This
says that the mutated huntingtin protein exerts its chief effects by
altering brain development in the uterus and during infancy, making the
brain more vulnerable to the normal degenerative processes of ageing . But in early life, these brain changes may cause higher intelligence quotient (IQ).
Much of the recent evidence for this idea comes from a study led by Schultz’s University of Iowa colleague Peggy Nopoulos , a co‑author of the new paper. She has been following the health of children from Huntington’s-affected families since 2006.
Brain scans show that in those children with the Huntington’s
mutation, certain areas of their brains are slightly larger than usual
in childhood, but become smaller from about their late 20s, presumably
due to cells beginning to die. In 2019, the team published this finding in relation to the striatum ,
in the centre of the brain. This area, which is involved in controlling
movements as well as many other cognitive functions, is an established
site of cell death in Huntington’s disease.
The team has also shown that the mutation causes an increase in the
size of the cortex, the outer layer of the brain more commonly linked
with cognitive abilities, although this data hasn’t yet been published,
says Nopoulos.
The same group of children also underwent a range of cognitive tests, which found a link between the mutation and their General Ability Index score , a children’s version of the standard IQ scale.
In this study of 316 children, the team didn’t just class the
children as having the mutation or not, but also counted the number of
triplet repeats in the gene. The researchers found the highest cognitive
ability was about 113 points – well above the average of around 100
points – being seen in children with 40 or 41 repeats, which means they
would develop Huntington’s. This is compared with a score of 105 for
those with 15 to 19 repeats who haven’t inherited the mutated gene.
It is impossible to prove that the Huntington’s mutation was selected for by evolution ,
but greater intelligence presumably helps people to survive and
reproduce. And as the condition’s first symptoms tend to start only in
people’s 30s or later, they could have had several children by then.
Intriguingly, other researchers studying people without Huntington’s,
who all have 35 or fewer triplet repeats, found that it is more common
to have higher numbers of repeats than would be expected by chance, as if that has a selective advantage .
If the new idea is right, it would change how we think about
intelligence, as no other single gene has been discovered with such a
large positive effect on IQ. But more evidence may be needed to convince
brain geneticists. “It would be very exciting if it were true,” says Robert Plomin at King’s College London.
To be convinced, Plomin wants to see the finding replicated in larger studies, mainly because all intelligence -related genetic research to date has found that, while it is highly heritable, the trait is generally influenced by hundreds of genes , each with a tiny effect – of much less than 0.1 of an IQ point.
On the other hand, these studies haven’t counted the number of
repeats in the Huntington’s gene, says Nopoulos. Instead, they focus on
the more common kinds of genetic variation, such as when one DNA letter
is replaced by another. “This is a whole different way of looking at the
genetic code,” she says.
Whether or not the Huntington’s mutation boosts IQ, other kinds of
evidence support the idea that the normal function of the huntingtin
protein is to help build a developing brain. For instance, a study published in August looking at young adults with the mutation found that the brain cells that die first have a higher level of activity for genes involved in the organ’s development.
If altered brain development is the root cause of the condition’s
symptoms, that could be bad news for efforts to develop a treatment, as
many therapies in the works are designed to lower levels of the
huntingtin protein.
However, the toxicity idea has support from animal studies, says Carlos Estevez-Fraga
at University College London, who was involved in the young adults
study. He says it is possible that the mutation has dual effects:
altering early brain development and inducing later-life toxicity. “It
is reasonable to think that lowering it in the adult brain has the
potential for benefit.”
So far, three huntingtin-lowering strategies have failed in clinical
trials, including a drug called tominersen, which didn’t improve
Huntington’s symptoms despite cutting levels of the protein in
cerebrospinal fluid.
It is too soon to know if the whole strategy is flawed, but one thing
most researchers agree on is that we need to know more about the
natural functions of the non-mutated form of the huntingtin protein.
“That will be a very, very important piece of the puzzle,” says Schultz.
Zdroj: New Scientist
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Cannabis addiction may be partly down to genetics
An analysis of genetic data from more than 1 million people shows that those with cannabis use disorder share similar markers.
People who develop a cannabis use disorder share certain genetic markers, and that pattern holds across racial groups, according to the largest study of its kind.
Around one-third of people who self-identify as regular cannabis
users will go on to develop cannabis use disorder – the continued,
regular use of the drug despite a negative impact on one’s life. People
with cannabis use disorder often find it difficult to quit the drug and
need higher and higher doses to feel an effect.
“It’s possible that you could be only a weekend user and still meet
the criteria for cannabis use disorder, but it’s pretty unlikely,” says Joel Gelernter at the Yale School of Medicine. “These are mostly much more frequent users.”
The genetic link to problematic cannabis use has been explored
before, but this latest research is the first to look at a large sample
across different racial backgrounds. Researchers combed the genetic
information of more than 1 million individuals registered in the Million
Veteran Program, which collects data from military members in the US.
Their sample included a range of ancestry groups ,
such as European, African, East Asian and mixed race. Then, using a
technique called genetic correlation, they compared variations in each
person’s DNA to see if these were associated with a certain trait: in
this case, cannabis use disorder.
“We found that the pattern was very close to identical across the different ancestries,” says Dan Levey ,
also at the Yale School of Medicine. They compared variations in each
person’s DNA and found that some were associated with a certain trait.
For example, in people with European ancestry, strong expression of a
neuronal receptor called CHRNA2 was associated with a higher risk of
developing cannabis use disorder.
The researchers also analysed health records and found a link between
lung cancer and developing cannabis use disorder for those with European
ancestry, even when controlling for cigarette use. Gelernter says that,
as a result, we may see a rise in lung cancer cases – which often take
years to diagnose – alongside the rise in the popularity of cannabis.
“If smoking pot does lead to increased risk for lung cancer, the uptick
won’t be observable until decades from now,” says Gelernter. “This is
something that people should be on the lookout for.”
Zdroj: New Scientist
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Sickle cell CRISPR 'cure' is the start of a revolution in medicine
The approval of a first CRISPR treatment, for sickle cell disease and beta thalassemia, is just the start for a technology still in its infancy
Just 13 years after the CRISPR gene-editing technique was described, the first medical treatment to make use of it has been approved. On 15 November, the UK Medicines and Healthcare products Regulatory Agency authorised a treatment that can effectively cure sickle cell disease and transfusion-dependent beta thalassemia for people aged 12 and over. The US and European Union are expected to approve it soon too.
It is a momentous step forward – and it is just the start. The treatment, called Casgevy, is based on a first-generation CRISPR technique. Improved versions of CRISPR already being tested in people promise to be safer, cheaper and more effective. Meanwhile, some researchers are trying to create even better gene-editing tools that could make CRISPR redundant.
If these efforts succeed, gene editing could soon be used to treat and prevent many common conditions, such as heart disease, as well as inherited ones. It is also probably the best hope for greatly extending our healthy lifespans and is already helping to treat some cancers .
Researchers had developed several gene-editing techniques before CRISPR, but creating the necessary tools was extremely difficult and expensive. The problem lay in the first step: finding the bit of DNA you want to change.
Early gene-editing techniques required proteins to be designed with the right shape to bind to specific DNA sequences. With CRISPR, the editing protein remains the same, finding the desired target with the help of a “guide RNA” with a matching sequence.
Because RNAs are cheap and easy to make, thousands of labs worldwide were able to start using CRISPR. However, the standard form is more of an eraser than an editor. CRISPR’s Cas9 protein just cuts DNA at a specific site and when the cell tries to repair the cut, it introduces mutations.
“The native function of CRISPR is to destroy, not to edit,” says Stephen Tang at Columbia University in New York, who was not involved in research related to CRISPR for sickle cell disease or beta thalassemia.
But destruction can sometimes cure. Sickle cell disease and beta thalassemia are caused by mutations in the adult form of haemoglobin, the oxygen-carrying protein in our blood. Casgevy works by destroying the “off switch” that halts the production of fetal haemoglobin as we get older.
The treatment involves removing blood stem cells from the body, editing them and replacing them. This removal is done for two reasons.
Firstly, we still lack effective ways to deliver CRISPR machinery to a high enough proportion of specific cell types in the body, such as blood stem cells. Secondly, when cells are edited outside the body, some checks for potentially dangerous unwanted mutations can be done before reimplanting them.
The downside is this is very expensive, because of all the hospital visits and lab time required for personalised treatments. The ideal would be an off-the-shelf treatment that can be given as an injection to anyone with a certain condition, editing only the cell types that need altering and making specific edits without introducing random mutations.
That means not relying on cells’ repair mechanisms to do the editing. “We need tools where all the components of the gene-editing process are under our control,” says Tang.
The good news is that we are already part of the way there. Modified forms of CRISPR known as base editing and prime editing can alter DNA directly. On 12 November, it was announced that CRISPR base editors injected directly into people’s bodies in a small, initial trial had lowered their cholesterol levels .
This approach works because it involves editing liver cells and the liver is the easiest organ to deliver things to due to its blood-cleaning function. However, rapid progress is being made in targeting other organs.
Base editing and prime editing are limited to making tiny changes, though. That is why Tang’s team and others are creating new gene editors based on so-called jumping genes. Also known as transposons, these are DNA sequences that move from one location on the genome to another. These editors will be able to add or remove large stretches of DNA containing entire genes. Tang thinks this approach will prove superior, pointing out that our genomes have already been extensively modified by transposons.
What has been remarkable about gene editing is the speed at which the technology has advanced since CRISPR’s inception – and there is no sign of it slowing.
Zdroj: New Scientist
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One-time CRISPR treatment could permanently lower cholesterol
A small trial of a cholesterol-lowering treatment based on CRISPR gene
editing has produced promising results, but there are questions over
safety
A CRISPR gene-editing treatment has lowered cholesterol
levels in a small, initial trial involving 10 people. The effect has
lasted for six months since the first participant was treated, and the
expectation is that it will be permanent – but a heart attack in one person has raised safety concerns.
The trial, carried out in New Zealand, involved people with an
inherited disease that results in very high cholesterol levels and so a
very high risk of heart disease. However, the company developing the
treatment, Verve Therapeutics in Boston, hopes its one-off treatment
could eventually replace cholesterol-lowering drugs like statins.
“It’s early but could open the way for an entire new way to treat heart disease,” CEO Sek Kathiresan said on X.
In the three people given the highest doses, levels of LDL
cholesterol (LDL-C), which is linked to heart disease risk, fell between
39 and 55 per cent.
For now, though, questions remain about safety. One of the three
people who received a high dose had a heart attack a day after being
treated that might have been related to the treatment, but could also
have been due to their underlying disease, Verve said in a press release announcing the results.
The company is
planning further small trials of the higher dose levels in the UK and
New Zealand, and aims to do a larger, randomised controlled trial if
those go well. This will provide more definitive evidence on the safety
issue.
“These data confirm our hypothesis that a single-course gene editing
medicine has the potential to induce meaningful and durable reductions
in LDL-C,” Andrew Bellinger, the chief scientific officer at Verve, said
in the press release.
The treatment involves a variant of CRISPR gene editing known as base editing .
The standard CRISPR technique uses an enzyme to cut the DNA in the
genome of cells, which can result in potentially dangerous mutations.
Base editing involves modifying CRISPR enzymes so they change one DNA
letter to another without cutting the DNA. This greatly reduces the
risk of unwanted mutations, though it doesn’t entirely eliminate it.
Almost all CRISPR treatments so far have involved removing cells from
an individual, modifying them in a lab and then putting them back into
the body. Such personalised treatments are extremely expensive.
But because CRISPR base editing is safer, Verve is injecting the
CRISPR machinery into people’s bodies, in the form of lipid
nanoparticles carrying RNAs – similar to the mRNA covid-19 vaccines . That means the treatment could be cheaper and much more widely available if it proves safe.
Inside the body, almost all the lipid nanoparticles are mopped up by
liver cells, which then produce the base-editing protein that disables a
gene for a protein called PCSK9. The PCSK9 protein breaks down an
enzyme that removes cholesterol from the blood, so disabling PCSK9
lowers cholesterol.
Some people have natural mutations that disable PCSK9 , and they are less likely to get heart disease without any apparent ill effects.
While this initial trial was very small, the fact that those given
the highest doses saw large reductions in cholesterol, whereas those
given the smallest doses had much lower or insignificant changes
suggests the treatment is effective, according to Bellinger.
“It’s a hugely important milestone for the field,” tweeted John Evans at Beam Therapeutics, another company working on base-editing treatments.
According to Sean Wu
at Stanford University in California, it is possible that inflammation
caused by the lipid nanoparticles led to the heart attack, but this
remains unclear.
Zdroj: New Scientist
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Yeast has half its DNA rewritten in quest for synthetic complex cells
A team aiming to produce the first complex cell with an entirely
synthetic genome has created a strain of yeast with half of its
chromosomes designed from scratch
A large international team has created a strain of yeast in which
half of the 16 chromosomes are synthetic ones that have been redesigned
and created from scratch, in a major step towards creating the first
complex cell with an entirely synthetic genome.
“We’re more than halfway there now,” says project leader Jef Boeke at New York University Langone Health.
The idea of the project is both to gain a better understanding of
complex cells and to create yeast strains for industrial use, for
instance for making biofuels. “We think it’s going to be an amazing
platform for optimising yeast for producing products that are useful to
humankind,” says Boeke.
Other groups have created viruses and bacteria
with entire genomes synthesised from scratch, but yeast is more
challenging because it is a complex or eukaryotic cell, like those in
all plants and animals .
Complex cells have larger genomes divided into many different
chromosomes rather than the single small genome typical of bacterial
cells.
The synthetic versions
of all 16 yeast chromosomes are now complete, but putting all 16
together in a single yeast strain could take another year or so, says
Boeke. “When we get all those chromosomes into a single strain, we’re
going to be able to do a whole bunch of new things we couldn’t do
before.”
The main issue
isn’t physically assembling this strain, but “debugging” the synthetic
chromosomes. “As we build things, we discover these bugs, and these are
the result of changes we intentionally made that, according to what we
know about biology, should not have had a negative impact but it turns
out that they do,” he says.
Eukaryotic cells have a lot more repetitive or “junk” DNA than bacteria. There are even bits of junk DNA within genes, called introns , that have to be spliced out of the RNA copies of genes that carry the instructions for making proteins.
The team has removed most of this repetitive DNA, making the
synthetic chromosomes around 10 per cent smaller. “We believe that by
removing repetitive DNA we will make a fundamentally more stable base
for biotechnology,” says Boeke.
Once all the introns are removed, the team plans to remove the RNA splicing machinery as well.
The team has also added 3000 sites to the genome where they can
trigger recombination, where pieces of code are exchanged between
different chromosomes. The idea is to rapidly evolve strains for industrial applications.
“It’s kind of like shuffling a deck of cards”, says Boeke. “The
scramble system is essentially evolution on hyperspeed, but we can
switch it on and off.”
There is also an entirely new 17th chromosome containing all the
genes for molecules involved in protein synthesis called tRNAs. Cells
need to make lots of tRNAs, but because the genes are aligned in
different directions on natural chromosomes, enzymes can crash into each
other and break the DNA.
On the new artificial chromosome, all the genes are aligned in the
same direction to prevent breaks. “There’s nothing like that in nature,
that’s for sure,” says Boeke.
The synthetic yeast should have some kind of biocontainment system to ensure it cannot survive and spread in the wild, says Geoffrey Taghon at the US National Institute of Standards and Technology, who isn’t part of the team.
“Even if remote, the risk of an escaped, potentially invasive
synthetic organism is still a serious one that warrants some
consideration,” says Taghon.
“We are very much in agreement that adding some sort of containment
system to the final strain would be ideal,” says Boeke. The team has
already made changes that mean the synthetic yeast couldn’t outcompete wild ones , he says.
The technology developed to create the yeast is now being used to
rewrite parts of the mouse genome, to create more human-like mouse
strains for medical research. However, because the mouse genome is 200
times bigger than that of yeast, creating an entirely synthetic mouse
isn’t practical with existing technology.
“Unless there’s some major speed-ups, it’s not going to happen in my
lifetime,” says Boeke. “But I wouldn’t rule it out. Never underestimate
the power of technology development.”
Zdroj: New Scientist
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Humans caught more diseases after we domesticated animals
Analysis of DNA from human remains up to 37,000 years old shows that
more infectious diseases jumped from animals to people after the dawn of
farming
DNA from the bones and teeth of 1300 people who died up to 37,000
years ago has revealed what infectious diseases some of them had when
they died – as well as how the incidence of some of these diseases
changed over time. The findings show that animal diseases were much more
likely to jump to humans after the advent of farming.
This is the first direct evidence that the domestication of animals
led to humans acquiring more infectious diseases, according to Eske Willerslev
at the University of Copenhagen in Denmark and his colleagues. This
“profoundly impacted global human health and history throughout the
millennia and continues today”, the team writes.
The study looked at a wide range of microbes in human remains from all over the world
and many different times, making it the largest and most comprehensive
of its kind so far. The oldest human remains were from around 37,000
years ago, but most were between several thousand and a few hundred
years old.
The researchers exploited the fact that it is becoming common to sequence the genomes of ancient people , and that the DNA of bacteria or DNA viruses present in the bones or teeth gets sequenced, too.
These microbial sequences are filtered out when ancient human genomes are reassembled .
To identify them, the team analysed raw data from the sequencing of
more than 1300 ancient human genomes, including 130 that haven’t yet
been published.
Most of the microbial DNA the researchers found was from soil
bacteria, suggesting bacteria got into the bones after burial. In teeth,
much of the microbial DNA came from bacteria known to live in people’s
mouths.
However, the team was also able to identify many disease-causing
bacteria and viruses that were in the blood of people before they died
and may have caused or contributed to their death.
The most common was the bacterium that causes the plague, Yersinia pestis ,
found in 39 people, which is 3 per cent of the remains. This bacterium
mainly infects rodents, but can be spread to people by fleas.
The oldest plague cases were in three people who lived in various
parts of Asia around 5700 years ago. The bacterium was also found in a
person entombed on Orkney in Scotland around 4800 years ago – about 800
years before the previous earliest known case of the plague in Britain .
Overall, the team found lots of plague cases between 6000 and 3000
years ago. Then there was a gap until 2000 years ago, when there was a
wave lasting for a few centuries, then another gap until a second wave
corresponding with the medieval “Black Death” plague pandemic .
The researchers think that the gaps where no plague cases were
detected “represent an actual reduction in the underlying incidence of
the disease”. Their findings fit with other studies suggesting that the
early form of plague wasn’t very transmissible and died out, to be replaced later by more transmissible strains that caused pandemics.
The next most common microbe was Borrelia recurrentis , which causes a disease spread by body lice called
louse-borne relapsing fever. This disease is now rare, but the team
found it in 31 people, 2.3 per cent of the total, suggesting it was
widespread in the past.
The first cases the researchers found were in Scandinavia around 4500 years ago, implying B. recurrentis first jumped from animals into people around this time, but it isn’t clear what the original animal source was.
Other diseases identified include malaria , hepatitis B, leprosy and leptospirosis, also known as Weil’s disease.
The researchers divided the kinds of microbes they found into five
broad types, including zoonotic diseases, those that jumped from animals
into humans. They found there was an increase in zoonotic diseases from
around 6000 years ago, but not of any of the other four types.
“The risk and extent of zoonotic pathogen transmission likely
increased with the adoption of more widespread husbandry practices and
pastoralism,” the study says.
Pontus Skoglund
at the Francis Crick Institute in London says the work is “promising”.
While it is possible to identify trends in the incidence of pathogens in
the distant past, studies like this need to take account of potential
biases, he says. For instance, people who died of disease may have been buried in different ways to the standard, or cremated instead.
Another issue with the study is that standard DNA sequencing misses RNA viruses, such as flu and coronaviruses , which may have caused major outbreaks in the past. Specific techniques are needed to detect these viruses.
Willerslev declined to discuss the findings prior to publication in a peer-reviewed journal.
Zdroj: New Scientist
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Molecular engineers successfully create a working DNA 'nanomachine'
Molecular engineers
have devised an unimaginably tiny machine at the nanometer (nm) scale
similar to molecular robots, which can move and work together in a
controlled manner.
Petr Šulc, an assistant professor at Arizona
State University's School of Molecular Sciences, worked with Professor
Michael Famulok from the University of Bonn, Germany, and Professor Nils
Walter from the University of Michigan on this project.
DNA chemical energy regulating motion The
team designed and developed nano assemblies at the molecular level.
They devised a DNA nanomachine measuring 70 nm × 70 nm × 12 nm, driven
by the chemical energy of DNA-templated RNA-transcription-consuming
nucleoside triphosphates, according to the study.
This nanomachine
uses chemical energy to generate controlled, rhythmic pulsating motion.
This advancement illustrated the potential for creating precise,
controllable nanoscale devices with applications in various fields such
as nanotechnology, medicine, and materials science.
Zdroj: Interesting Engineering
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Gene-edited chickens are partially resistant to bird flu
Scientists
from the University of Edinburgh’s Roslin Institute have successfully
gene-edited chickens to make them partially resistant to the bird flu
but experts argue that only full immunity can see the danger of the
virus eradicated.
This is according to a report by BBC News published this week.
Influenza A viruses, which are responsible for causing bird flu, can
be divided into many subtypes based on the surface proteins
hemagglutinin (H) and neuraminidase (N). While certain bird flu subtypes
are less dangerous, others are more virulent and capable of causing
serious illness.
Direct contact with diseased birds or with their droppings, saliva,
or respiratory secretions is the main way that bird flu viruses are
transmitted. In rare instances, the infection can spread through tainted
food, water, gear, and clothing.
Serious sickness and death
The symptoms of infected birds might range from minor or asymptomatic
illnesses to serious sickness and death. Indicators of an infection can
include neurological signs, swollen eyes, a swollen head and neck, and
respiratory difficulty.
In the worst of cases, bird flu can be transmitted to humans. Bird
flu infections in humans can range in severity from moderate to extreme,
with symptoms that are comparable to those of the seasonal flu. In
certain cases, however, they can cause serious respiratory illness or
even death.
The newly gene-enhanced chickens were reported to show no negative
side effects from the bird flu two years after being infected. However, a
large dose of the virus did infect half the chickens, resulting in an
infection and showing that they were not completely immune despite
having enhanced resistance to the virus.
This caused worry for scientists who claimed that even if any
improvement in bird flu resistance is to be commended, only a treatment
that guarantees total immunity can be put into action in real-world
situations.
Worries of a more powerful virus
Any intervention that develops only partial resistance would also
drive the virus to mutate in order to fight back, which could result in a
more powerful virus that could be more damaging to humans.
Some subtypes of avian influenza, such as H5N1 and H7N9, have already
raised public concerns about the potential for a global pandemic if
they were to acquire the ability to transmit efficiently from human to
human. Aggravating these strains could be extremely problematic.
The scientists behind the new development, however, claim that full
immunity is well within their reach. They have thus far managed to edit
two out of the three genes responsible for the bird flu and feel
confident that they can tackle the third one within the next few years.
“When we did these edits in the cells there was no growth of the
virus at all. The changes stopped all replication of the flu,” Prof Mike
McGrew, of the Roslin Institute, told BBC News .
”I am extremely confident that editing the three genes will give full immunity.”
Zdroj: Interesting Engineering
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Google DeepMind's new AI tool can predict genetic diseases
Genetic mutations are changes to our DNA sequence. This happens when cells make copies of themselves during cell division. Mutation is the ultimate source of human genetic variation and has evolutionary and disease genetics implications. A mutation affecting our genes might give birth to a genetic disorder. But just because you have a mutation doesn’t mean it will be a genetic disorder.
That is why researchers at DeepMind, the artificial intelligence arm of Google, have announced that they have trained a machine learning model called AlphaMissense to classify which DNA variations in our genomes are likely to cause disease.
Zdroj: Interesting Engineering
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Genetic Testing for Cancer Susceptibility
Approximately 10% of patients diagnosed with cancer have a germline variant in a gene that increases susceptibility to cancer. The most common examples include germline pathogenic variants (mutations) in BRCA1 and BRCA2, which are associated with an increased risk of breast, ovarian, pancreatic, and prostate cancer, and germline pathogenic variants in MLH1, MSH2, MSH6, and PMS2 (Lynch syndrome), which are associated with increased risk of colorectal cancer, endometrial cancer, and other cancer types.
More than 100 genes that increase susceptibility to cancer (with varied levels of penetrance and association with cancer susceptibility) have been described. The prevalence of these germline genetic variants varies by cancer type, ranging from 4% to 6% in patients with lung cancer, esophageal cancer, and head and neck cancer to 30% for male patients with breast cancer.
In patients diagnosed with cancer, testing for gene variants associated with increased cancer susceptibility is important for at least 2 reasons. First, testing informs the most optimal treatment for a patient with cancer. Second, testing helps identify relatives who may have inherited genes that increase their cancer susceptibility. Identifying these genes could improve outcomes by increasing cancer screening and risk-reducing measures such as preventive surgery. With the advent of next-generation sequencing technologies, genetic testing for cancer risk has shifted from sequential, single-gene testing to multiple-panel genetic testing using blood or saliva. These tests require only 2 to 4 weeks for results and are performed by several large commercial laboratories.
For patients diagnosed with cancer for whom practice guidelines recommend genetic susceptibility testing, multiple-panel genetic testing is covered by most health insurance entities. Practice guidelines now recommend testing for inherited cancer susceptibility genes for all patients with ovarian, male breast, and pancreatic cancer. For other cancer types, including female breast, prostate, and colorectal, the criteria for testing have expanded, with more practice guidelines now advocating for genetic susceptibility testing for all patients or increasing subsets of patients.
Genetic testing for inherited cancer syndromes has become an integral component of cancer care because it directly affects management and therapy. In 2014, the first poly(adenosine diphosphate–ribose) polymerase inhibitor was approved by the US Food and Drug Administration for BRCA -associated ovarian cancer, and more recently approval has been expanded to include treatment for BRCA -associated breast cancer, pancreatic cancer, and prostate cancer. At the time of breast cancer diagnosis, identifying a high-risk variant in a susceptibility gene such as BRCA1 or BRCA2 may encourage some women to select risk-reducing bilateral mastectomy or risk-reducing salpingo-oophorectomy. Patients with variants in cancer-predisposing genes are also candidates for more frequent or intensive cancer screening. Examples include colonoscopy every 1 to 2 years in Lynch syndrome, breast magnetic resonance imaging in females with BRCA1 and BRCA2 genetic variants, and whole-body magnetic resonance imaging in patients with Li-Fraumeni syndrome.
In this issue of JAMA , Kurian et al report the rate of genetic testing in inherited cancer susceptibility in more than 1.36 million patients diagnosed with cancer between 2013 and 2019. Kurian et al linked genetic test results from the 4 major commercial laboratories to incident cancer diagnoses reported to the California and Georgia Surveillance, Epidemiology, and End Results tumor registries. Kurian et al report that only 6.8% of patients with cancer underwent genetic susceptibility testing within 2 years of the cancer diagnosis. The testing rates were higher for male breast cancer and ovarian cancer, for which practice guidelines recommend universal testing for all diagnosed patients.
However, even for ovarian cancer, for which universal genetic testing has been recommended since 2010, the rate of genetic testing was only 38.6%. The highest rate of testing was 50% for men with breast cancer. For pancreatic cancer, the rate of genetic testing increased from 1.2% in 2013 to 18.6% in 2019, the year that universal testing for this tumor type was first recommended. Previously, testing was recommended only for patients meeting specific family history criteria, or with specific ancestries known to be associated with higher rates of genetic susceptibility. Because tumor registries do not record family histories, the number of people with cancer who met practice guideline criteria but who did not undergo genetic testing could not be evaluated. Some cancer patients may have obtained genetic testing through direct-to-consumer laboratories and would not have been counted among the patients with genetic testing in the analyses. Nonetheless, the low rates of cancer genetic testing reported by Kurian et al raise concern and should stimulate interventions to increase rates of genetic testing with the goal of reducing cancer burden.
A strength of the study by Kurian et al was measurement of testing at the population level using the California and Georgia statewide tumor registries. When the results were analyzed by race and ethnicity, 22% of Asian patients, 25% of Black patients, and 23% of Hispanic patients underwent genetic testing for male breast cancer, female breast cancer, or ovarian cancer compared with 31% of non-Hispanic White patients with these cancer types. Uncertain genetic test results (defined as a result that could not clearly indicate whether the variant was related to cancer), which can result in suboptimal clinical management and increased patient anxiety, were significantly more common in non-White patients. The combination of low genetic testing and more frequent identification of variants of uncertain clinical significance can perpetuate existing disparities.
The analyses by Kurian et al did not identify reasons for underuse of genetic testing. Potential explanations can be divided into at least 2 categories. First, there are health care system–related barriers (eg, lack of timely access to genetic counseling). Many health systems do not employ genetic counselors and there is a US shortage of these professionals. Second, there are patient factors, such as preoccupation with coping with cancer treatment, lack of awareness or interest, mistrust, or fear of the potential consequences of testing, which may contribute to low genetic testing rates. These health care system–related and patient-related factors are even greater in vulnerable populations, including racial and ethnic minority groups, residents of rural regions, and patients with low health literacy.
New care delivery models are needed to improve the rates of cancer susceptibility genetic testing. In the US, this is a priority of the National Cancer Institute’s Moonshot program. First, clinicians must be familiar with practice guidelines indicating when cancer susceptibility genetic testing is indicated. Ensuring consistency of practice guidelines sponsored by professional societies may facilitate this goal. Clinical decision support tools integrated within electronic records could systematically identify patients eligible for cancer genetic testing. Automated clinician notifications of eligibility and testing criteria integrated in pathology reports for cancer types with inherited susceptibility genes may increase genetic test ordering by clinicians.
Second, clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing. Traditionally, cancer susceptibility genetic testing has required a visit with a genetic counselor before testing to obtain informed consent and ensure clear understanding of the consequences for the patient and their relatives if a cancer susceptibility variant is identified. However, this model of delivery for genetic counseling is neither efficient nor sustainable. Patients must have access to clear, reliable, and convenient sources of information to inform their decision to undergo testing and understand and manage test results. An individual visit with a genetic counselor should not be a prerequisite to testing.
An alternative to the traditional genetic counseling pretesting visit is a point-of-care testing approach, also known as mainstreaming. In this model, nongenetic health care clinicians (usually surgeons or oncologists) provide a brief educational session, obtain consent, and order genetic testing during a single medical center visit. Several studies of patients with breast, ovarian, pancreatic, and prostate cancer demonstrated excellent feasibility and acceptability for this approach. The results (especially for positive or uncertain test results) can also be delivered by a genetic counselor or other clinicians trained in cancer genetics.
To ensure patients receive necessary information, pretest (and potentially posttest) genetic counseling can be delivered using digital methods such as web-accessible videos. Genetic counselors can explain inherited cancer susceptibility in the patient’s preferred language. Videos can be supplemented by telehealth visits with genetic counselors for patients requiring individually tailored information. Experience suggests that many patients agree to germline testing after viewing a short video. Comprehension could be evaluated with brief surveys. This approach can make genetic counseling and genetic testing widely available at minimal expense.
In the future, artificial intelligence–supported chatbots may respond to patients’ questions about genetic testing. Many genetic counseling interactions currently are performed using telehealth and this trend does not appear to be waning as the COVID-19 pandemic subsides. Telehealth is convenient, efficient, and may help increase genetic testing rates. Permanent elimination of regulatory barriers for telemedicine genetic counseling across the US would help sustain access to genetic counseling.
Identification of gene variants associated with increased cancer susceptibility can improve outcomes for both cancer patients and family members. As data from Kurian et al highlight, genetic cancer susceptibility testing is underused, and this is a missed opportunity to decrease the population-level burden of cancer. With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented.
Zdroj: JAMA
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Germline Genetic Testing After Cancer Diagnosis
Importance Germline genetic testing is recommended by practice guidelines for patients diagnosed with cancer to enable genetically targeted treatment and identify relatives who may benefit from personalized cancer screening and prevention.
Objective To describe the prevalence of germline genetic testing among patients diagnosed with cancer in California and Georgia between 2013 and 2019.
Design, Setting, and Participants Observational study including patients aged 20 years or older who had been diagnosed with any type of cancer between January 1, 2013, and March 31, 2019, that was reported to statewide Surveillance, Epidemiology, and End Results registries in California and Georgia. These patients were linked to genetic testing results from 4 laboratories that performed most germline testing for California and Georgia.
Main Outcomes and Measures The primary outcome was germline genetic testing within 2 years of a cancer diagnosis. Testing trends were analyzed with logistic regression modeling. The results of sequencing each gene, including variants associated with increased cancer risk (pathogenic results) and variants whose cancer risk association was unknown (uncertain results), were evaluated. The genes were categorized according to their primary cancer association, including breast or ovarian, gastrointestinal, and other, and whether practice guidelines recommended germline testing.
Results Among 1 369 602 patients diagnosed with cancer between 2013 and 2019 in California and Georgia, 93 052 (6.8%) underwent germline testing through March 31, 2021. The proportion of patients tested varied by cancer type: male breast (50%), ovarian (38.6%), female breast (26%), multiple (7.5%), endometrial (6.4%), pancreatic (5.6%), colorectal (5.6%), prostate (1.1%), and lung (0.3%). In a logistic regression model, compared with the 31% (95% CI, 30%-31%) of non-Hispanic White patients with male breast cancer, female breast cancer, or ovarian cancer who underwent testing, patients of other races and ethnicities underwent testing less often: 22% (95% CI, 21%-22%) of Asian patients, 25% (95% CI, 24%-25%) of Black patients, and 23% (95% CI, 23%-23%) of Hispanic patients (P < .001 using the χ2 test). Of all pathogenic results, 67.5% to 94.9% of variants were identified in genes for which practice guidelines recommend testing and 68.3% to 83.8% of variants were identified in genes associated with the diagnosed cancer type.
Conclusions and Relevance Among patients diagnosed with cancer in California and Georgia between 2013 and 2019, only 6.8% underwent germline genetic testing. Compared with non-Hispanic White patients, rates of testing were lower among Asian, Black, and Hispanic patients.
Zdroj: JAMA
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An unknown Siberian community abruptly disappeared, new study finds
Early on in human history, it is commonly documented that humans moved from North Asia to North America over the Bering Strait. Last week, a study claimed that people might have crossed Beringia earlier than we thought due to climate change. According to a new study published in Current Biology yesterday (Jan.12), genomes from ten individuals with ages up to 7,500 years old demonstrate gene flow from people migrating from North America to North Asia (i.e in the opposite direction). The research team also looked at the remains of a prehistoric shaman who lived in western Siberia some 6,500 years ago. According to the current DNA analysis, this location is more than 900 miles (1,500 kilometers) west of the group with which he shared genetic links.A previously unknown population Their investigation identifies a hitherto unidentified early Holocene Siberian population that resided in the Neolithic Altai-Sayan region close to the border of Russia, China, Mongolia, and Kazakhstan. They were descendants from both Paleo-Siberian and Ancient North Eurasian (ANE) people, according to DNA research. “We describe a previously unknown hunter-gatherer population in the Altai as early as 7,500 years old, which is a mixture between two distinct groups that lived in Siberia during the last Ice Age,” says Cosimo Posth at the University of Tübingen, Germany, and senior author of the study. “The Altai hunter-gatherer group contributed to many contemporaneous and subsequent populations across North Asia, showing how great the mobility of those foraging communities was," he adds.The homeland of Denisovans As stated in the release, Posth also suggested that the Denisovans were also found here. Additionally, this area has played a significant role in human history as a crossroads for migrations of people throughout millennia between northern Siberia, Central Asia, and East Asia. The newly discovered gene pool might be the best source for the presumed ANE-related population that gave rise to Bronze Age populations from North and Inner Asia. This includes the Lake Baikal hunter-gatherers, the pastoralists connected to Okunevo, and the mummies from the Tarim Basin, researchers say. “The finding that surprised me the most is from an individual dated to a similar period as the other Altai hunter-gatherers but with a completely different genetic profile, showing genetic affinities to populations located in the Russian Far East,” says Ke Wang at Fudan University, China, and lead author of the study. “Interestingly, the Nizhnetytkesken individual was found in a cave containing rich burial goods with a religious costume and objects interpreted as possible representation of shamanism.” “It is not clear if the Nizhnetytkesken individual came from far away or the population from which he derived was located close by,” she says. “However, his grave goods appear different than other local archeological contexts implying mobility of both culturally and genetically diverse individuals into the Altai region.”Study abstract: The peopling history of North Asia remains largely unexplored due to the limited number of ancient genomes analyzed from this region. Here, we report genome-wide data of ten individuals dated to as early as 7,500 years before present from three regions in North Asia, namely Altai-Sayan, Russian Far East, and the Kamchatka Peninsula. Our analysis reveals a previously undescribed Middle Holocene Siberian gene pool in Neolithic Altai-Sayan hunter-gatherers as a genetic mixture between paleo-Siberian and ancient North Eurasian (ANE) ancestries. This distinctive gene pool represents an optimal source for the inferred ANE-related population that contributed to Bronze Age groups from North and Inner Asia, such as Lake Baikal hunter-gatherers, Okunevo-associated pastoralists, and possibly Tarim Basin populations. We find the presence of ancient Northeast Asian (ANA) ancestry—initially described in Neolithic groups from the Russian Far East—in another Neolithic Altai-Sayan individual associated with different cultural features, revealing the spread of ANA ancestry ∼1,500 km further to the west than previously observed. In the Russian Far East, we identify 7,000-year-old individuals that carry Jomon-associated ancestry indicating genetic links with hunter-gatherers in the Japanese archipelago. We also report multiple phases of Native American-related gene flow into northeastern Asia over the past 5,000 years, reaching the Kamchatka Peninsula and central Siberia. Our findings highlight largely interconnected population dynamics throughout North Asia from the Early Holocene onward.
Zdroj: Interesting Engineering
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Plan for microbes to eat Chernobyl's nuclear waste may be ruined
Researchers hoping to identify bacteria capable of consuming radioactive waste at the Chernobyl nuclear power plant fear their work has been destroyed by Russian troops. Researchers at the Chernobyl nuclear power plant in Ukraine had been looking for bacteria to eat radioactive waste – but they now fear that their work was irreparably lost during the Russian invasion of the facility. Anatolii Nosovskyi, director of the Institute for Safety Problems of Nuclear Power Plants (ISPNPP) – which carries out research in several labs at Chernobyl – said in a letter to the global scientific community, seen by New Scientist, that his staff are still unable to return to work despite Russian troops withdrawing from the plant earlier this month. A limited party was able to access laboratories on 12 April and found doors and windows broken and most scientific equipment looted, damaged or destroyed. Nosovskyi suggested that soldiers were tasked with collecting their data. “Almost all the computer equipment was taken to a separate premise where the looters removed the memory cards,” he wrote. ISPNPP researcher Olena Pareniuk has been in the city of Zhytomyr, around 130 kilometres west of Kyiv, for the past week after being first evacuated to Chernivtsi at the start of the invasion. Before the attack, she was attempting to identify bacteria that could consume radioactive waste within Chernobyl’s destroyed reactor, and she fears that her research will be impossible to resume. “The truth is that there are still scattered Russian troops in Chernobyl, so scientists and other people who are not military are not allowed there,” she says. “Also, the forests are mined, so it will take a while for us to come back to labs as usual. As for now, all our entrance permissions are stopped until further notice.” Pareniuk had been studying the microbial diversity of pools of water within the containment building around the destroyed reactor, but these pools have long since disappeared. “I still have a hope that my samples are in their fridge. It will be impossible to get those biodiversity samples for the second time,” she says. “We were trying to cultivate the specific microorganism that might ‘eat’ lava, concrete and steel constructions inside the arch and spent fuel storage. That might be restored, but it will take a lot of money, time and work.”Another ISPNPP researcher, Maxim Saveliev, is less optimistic. “We need to start near from zero mostly in all subjects, having people but no data, as all our hard discs have been stolen,” he says. Work at the laboratories is still on hold. In his letter, Nosovskyi said that budgets to rebuild and replace equipment won’t come while the country is at war, and will be difficult to secure even in the aftermath. He also said that the ISPNPP plans to launch a charitable fund asking scientific organisations around the world to help. Life is also difficult for other workers at the power plant. Pareniuk says that their shifts typically last around 12 hours, but that the rail route between the site and the town of Slavytych – where most workers live – passes through Belarus and is considered too risky because of the country’s alliance with Russia. “No one really wants to risk people’s life and send them to Belarus even for a couple of hours,” she says. The alternative route through Chernihiv, Kyiv, Bucha and Irpin is challenging because of downed bridges and shelled roads, meaning that a one-way journey itself may take longer than the shift, says Pareniuk.
Zdroj: New Scientist
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Our Ancestors Were Partying With Denisovans 14,500 Years Ago
Up to 8% of our DNA comes from Denisovans who lived alongside Homo sapiens and Neanderthals in Asia.
The bone was from an entirely new type of human, or hominin , and they were christened "Denisovans" after the cave in which the bone was found. The Denisovans, or Homo denisovan , now joined Homo sapiens and Neanderthals as a distinct form of humans.
In 2019, Greek archaeologist Katerina Douka and colleagues radiocarbon-dated the oldest specimens from Denisova Cave, and they came up with a startling age of between 195,000 and 122,700 years ago . When they radiocarbon-dated artifacts that were found within the cave, the date came in at a staggering 287,000 years ago .
Up until 2019, only Denisova Cave contained evidence of this elusive species, with specimens from five
distinct Denisovans having been found. Then, scientists at Lanzhou
University examined a partial mandible, or jaw bone, that had been part
of the university's collection since 2010.
Originally discovered in the Baishiya Karst Cave
in 1980 by a Buddhist monk, when scientists examined the jaw bone, they
discovered that it belonged to a Denisovan who lived over 160,000 years ago. That date is a full 100,000 years before the first modern humans arrived in the area.
Located on the Tibetan Plateau, the Baishiya Cave sits at a height of 10,760 feet (3,280 m ) above sea level, while the Denisova Cave is only 2,296 feet (700 m ) above sea level. Soil samples taken from the Baishiya Cave and analyzed at Arizona State University (ASU) indicated that Denisovans may have been occupying the cave up to 45,000 years ago .
That date is significant because it means that Denisovans and modern
humans were living side by side at the same time in central Asia.
Many forms of us Denisovans and Neanderthals split from modern humans about 804,000 years ago , then from each other about 640,000 years ago . This means that Denisovans are the descendants of an earlier migration of H. erectus
out of Africa and that they are completely distinct from modern humans
and Neanderthals. Indeed, the exceedingly large molars of Denisovans are
similar to those of Australopithecines .
This adds to the debate over whether Homo sapiens solely evolved in
Africa, or whether our evolution continued in Asia. Also found in the
Denisova Cave alongside the child's finger bone were bone tools, a
marble ring, an ivory ring, an ivory pendant, a red deer tooth pendant,
an elk tooth pendant, a chloritolite bracelet, and a bone needle. This
indicates that Denisovans may have been making sophisticated tools and
jewelry.
Denisovans are among us Denisovans definitely interbred with
modern humans, a fact that is borne out by modern Sherpas who live on
the Tibetan Plateau. At 13,123 feet (4,000 m )
above sea level, the Sherpas have a genetic adaptation to high
altitudes that came from Denisovans. This adaptation allows them to live
where oxygen levels are 40% less than that of the sea level.
Within
the cells of all of us are mitochondria, which are small, rod-like
power plants, and those of Sherpas are highly efficient at using oxygen.
Sherpas' muscles get more mileage out of less oxygen than any other
humans.
Statistical geneticist Sharon Browning
of the University of Washington in Seattle and colleagues have also
found traces of Denisovan DNA in populations throughout Australia and
Melanesia. Melanesia is comprised of the islands northeast of
Australia. Between 3% and 5% of the DNA of Aboriginal Australians and Melanesians is from Denisovans. Between 7% and 8% of the Papuans' DNA who live in Indonesia is from Denisovans.
Species interbreeding Modern humans and Denisovans may have interbred with one another as late as 14,500 years ago in New Guinea. Denisovans also interbred with Neanderthals, with about 17% of the Denisovan genome that was found in the Denisova Cave deriving from Neanderthals.
Of the five
Denisovan specimens found in Denisova Cave, one was a young woman who
has been nicknamed "Denny". She was a Denisovan/Neanderthal hybrid whose
father was a Denisovan and whose mother was a Neanderthal.
Several different species of animals can interbreed with one another,
however, their offspring are usually infertile. Examples of species
interbreeding include:
Zebra + any other Equine = Zebroid Lion + Tiger = Liger, produced by a male lion and a tigress, it is the largest of all known felinesBottlenose Dolphin + False Killer Whale = Wholphin , while reported in the wild, two exist at Sea Life Park in HawaiiGrizzly Bear + Polar Bear = Grolar Bear Domestic Cattle + American Bison = Beefalo, this cross has led to genetic pollution of American bison herdsServal Cat + Domestic Cat = Savannah Cat , first bred in 1986, in 2001 the International Cat Association accepted it as a new registered breedMale Donkey + Female Horse = Mule , known to be infertile, mules are patient, sure-footed, and hardyMale Dromedary Camel + Female Llama = Cama , first produced in 1998 at the Camel Reproduction Center in DubaiYak + Domestic Cattle = Dzo , they are larger and stronger than regular cattle or yaksWolf + Dog = Wolfdog , wolves are
usually bred to German Shepherds, Siberian Huskies, or Alaskan
Malamutes, and their behavioral characteristics are unknown. Ghost hominins Of all people living today, except those from sub-Saharan Africa, around 2.8% of our DNA comes from Neanderthals. However, when scientists at the University of Utah analyzed the genomes of Europeans, Asians, Neanderthals, and Denisovans, they concluded that the latter two must have mated with a super-archaic "ghost hominin" that had separated from Homo sapiens around 2 million years ago .
Candidates include Homo erectus and Homo heidelbergensis , and this interbreeding might have extended to up 600,000 years ago . Another
"ghost hominin" is found in the DNA of those living on the island of
Flores, and only in the DNA of short-statured people who live near the Liang Bua Cave . This cave is where fossils of Homo Floriensis , better known as the "Hobbit", have been found. A skeleton found in 2003 stood 3 feet 7 inches (1.1 m ) tall while stone tools also recovered in the cave date to between 50,000 and 190,000 years ago .
ASU's Charles Perreault told the Daily Mail
that, "... Denisovans, like Neanderthals, were not mere offshoots of
the human family tree. They were part of a web of now-extinct
populations that contributed to the current human gene pool and shaped
the evolution of our species in ways that we are only beginning to
understand."
Zdroj: web
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‘Softer’ form of CRISPR may edit genes more accurately
Gene editing with CRISPR can cause off-target mutations, but this seems to happen less often with an enzyme that cuts one of the strands of DNA instead of both. A new form of the genome-editing technique CRISPR could provide a more accurate way to edit mutations that cause genetic diseases. The approach, which was tested in fruit flies, fixes a genetic mutation on one copy of a chromosome by using the equivalent chromosome – inherited from the other parent – as a template. CRISPR usually works with a protein called Cas9, which acts as molecular scissors to cut through the two strands of a DNA molecule at the site of a targeted sequence. This can allow new DNA sequences to be inserted between the cuts to replace the mutated gene. However, this insertion usually works for less than 10 per cent of cells and insertions can occur in incorrect, or off-target, regions of the genome. Now, Ethan Bier and Annabel Guichard at the University of California, San Diego, and their colleagues have developed a new form of CRISPR that can more efficiently insert correct DNA sequences at the site of a mutation, with fewer off-target effects. “I was blown away,” says Bier. “In general, with existing CRISPR techniques, you have to worry about roughly 1 per cent of edits being mistakes or off-target. I would say that, in the case of our system, it would be more like 1 in 10,000.” The method uses a variant of the Cas9 enzyme called a nickase, which only cuts one strand of the DNA double helix. “We found that ‘softly’ nicking, or cutting, one strand of the DNA is even more efficient than making a clean double-stranded break,” says Bier. The researchers tested the approach in fruit flies that had a mutation that turned their eyes white instead of red. They found that the nickase system corrected the eye colour mutation in up to 65 per cent of cells, giving the flies red eyes. Standard CRISPR using Cas9 corrected the mutation in up to 30 per cent of cells, causing each eye to have a small patch of red. “It was a truly incredible moment. We knew we had found something absolutely amazing when we saw that right away,” says Guichard. The team didn’t introduce any extra pieces of DNA as a template for the cell to correct the mutation on the chromosome, so the molecular machinery must have used the other chromosome – inherited from the other parent – as a template. The team was able to confirm this was the case. DNA repair of one chromosome using the other corresponding chromosome was generally not thought to be possible. But recent findings suggest that this can occasionally occur under specific circumstances that have yet to be defined. “There’s accumulating evidence that when you create damage to one chromosome in a mammalian cell, then that somehow recruits the other chromosome. Then the region that’s broken gets the Band-Aid from the other chromosome,” says Bier. “We don’t really understand what is responsible for doing that. One of the exciting elements of the work is that it opens up an avenue of discovering the whole set of components that are responsible for this new category of repair.”
If it is proven to work in people, the approach could potentially repair any disease-associated genetic mutations that have a healthy copy on the matching chromosome. This means it won’t be able to fix mutations on the X chromosome in boys, men and transgender women, who lack a second copy of this sex chromosome. It also won’t work for people with the exact same disease-linked mutation on both chromosomes from each parent.
Zdroj: New Scientist
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Scientists Use Stem Cell Therapy for Spinal Cord Injuries
The team injected patients with their own bone marrow stem cells, noticing remarkable effects.
Injecting bone marrow stem cells in patients with spinal cord injuries significantly improved their motor functions.
Scientists from Yale University and Sapporo Medical University in Japan reported their findings in the Journal of Clinical Neurology and Neurosurgery on February 18.
How stem cell therapy helped The
stem cells were prepared from the patients' own bone marrow, and
injected intravenously back into the patients, with no side effects from
the therapy noted by the researchers. This was not a blind trial, and
no placebos were administered.
Over half of the patients
reported improved motor functions within weeks of the injections. Key
motor functions include walking and using hands.
The
patients in question had experienced non-penetrating spinal cord
injuries a few weeks prior to the study, which were caused by minor
falls or trauma. These injuries left them without motor function or
coordination, sensory loss, and bowel and bladder dysfunction.
This type of therapy isn't only ideal for spinal cord injuries, but also for brain injuries, such as strokes. As Jeffery Kocsis of Yale University said "Similar results with stem cells in patients with stroke increases our confidence that this approach may be clinically useful."
Adding
to this comment, Stephen Waxman from Yale University said "The idea
that we may be able to restore function after injury to the brain and
spinal cord using the patient’s own stem cells has intrigued us for
years. Now we have a hint, in humans, that it may be possible."
It's
still the early days of this stem cell therapy for spinal cord
injuries, and the authors of the study stress that further studies need
to be carried out before confirming the results of their initial,
unblinded trial — something that could take years.
It's still exciting news, as stem cell therapy has been researched for years as a potential remedy for such injuries. Just last year, the Mayo Clinic carried out trials
on stem cell therapy for spinal cord injuries. While in Japan, a few
eyebrows were raised in 2019 as the nation accepted stem cell therapy to
treat spinal cord injuries, perhaps a little prematurely some
scientists suggested in the journal Nature .
The remnants of a virus that plagued our mammal ancestors during the age of the dinosaurs have been found lurking in our genomes The remnants of a virus that plagued our mammal ancestors during the age of the dinosaurs have been found lurking in our genomesThe remnants of a virus that plagued our mammal ancestors during the age of the dinosaurs have been found lurking in our genomes
Zdroj: web
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People of European descent evolved resistance to TB over 10,000 years
Ancient DNA reveals that people of European ancestry have lost a gene variant linked to tuberculosis (TB) susceptibility over centuries.
TB is one of the world’s deadliest diseases and is caused by the Mycobacterium tuberculosis
bacterium. People whose DNA contains two copies of a genetic variant
called P1104A are more likely to develop symptoms of TB after being
infected with the bacterium.
To trace the frequency of P1104A over time, Gaspard Kerner at the
Pasteur Institute in France and his team analysed modern human DNA from
around the world and compared it with more than 1000 samples of ancient DNA from Europeans from the past 10,000 years.
They found that the variant first appeared in DNA in low
numbers around 8500 years ago in western Eurasia. Using simulations and
demographic models to date the origins and movements of this variant,
the team predicted it may have originated in the same region around
30,000 years ago, long before the existence of TB in Europe. “It may
have appeared randomly, like when animals have mutations in their
genome,” says Kerner.
It then spread across central Europe 5000 years ago, and reached its
highest frequency 3000 years ago, with around 10 per cent of the
population carrying P1104A.
Kerner says it was able to spread without affecting an individual’s susceptibility to TB during that time as many people would only have had one copy of the variant.
The frequency of the variant drastically decreased 2000 years ago,
around the time modern TB bacteria became common. This may be because it
was under strong negative selection from TB, Kerner says, as increasing
migration made people more likely to inherit two copies of the variant
and therefore become more susceptible to TB.
“Individuals carrying this mutation may have died faster than other
individuals,” he says. The spread of TB during this time may have been
aided by migration increasing populations and bringing new bacteria and
diseases to Europe.
While the variant is now uncommon in modern Europeans and Americans,
it is absent in African and eastern Asian populations. Kerner says this
is consistent with the findings that P1104A emerged in Eurasia and that
other genes may be behind the prevalence of TB in Africa and Asia today.
“People still get sick from TB, both in Europe and elsewhere,” says
Vegard Eldholm at the Norwegian Institute of Public Health. Around 10
per cent of those infected with the bacterium develop TB. “This might
reflect a long history of co-evolution, and humans having adapted to
contain the infection. But it takes time for evolution to purge the
gene,” Eldholm says.
Zdroj: New Scientist
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Scientists Use DNA Supercoiling Technique to Produce Muscles for Miniature Robots
The possible applications of this development are countless.
University of Wollongong (UOW) researchers have taken inspiration from DNA supercoiling to produce miniature muscles that can work with the tiniest of robots, according to a study published in Science Robotics . The innovation could revolutionize how we tackle miniature robotics.
"Our
work describes a new type of artificial muscle that mimics the way that
DNA molecules collapse when packing into the cell nucleus," Professor Geoffrey Spinks from UOW’s Australian Institute for Innovative Materials said in a statement.
"We
were able to create DNA-like unwinding by swelling twisted fibers.
Supercoiling occurred when the fiber ends were blocked against rotation.
We show that these new artificial muscles generate a large amount of
mechanical work."
Before you get too excited about the potential applications
of this new invention, it should be noted that the movements of these
new artificial muscles are still too slow at the moment to be put to
use.
"We have used hydrogels to generate the volume changes that drive the supercoiling but that response is inherently slow," Dr. Javad Foroughi from
UOW’s Faculty of Engineering and Information Sciences, co-author of the
research paper, said. The next step for the researchers will be to
speed up the response.
"We do believe that the
speed can be increased by making smaller diameter fibers, but right now
the applications are limited to those that need a slower response,"
Professor Spinks added.
So what could this development
mean for robotics? It may make current tiny robots more agile by
allowing them more range of motion. For instance, we can imagine it
being applied to HAMR-JR robots to increase their agility.
Perhaps, it could even be used in the case of miniature robots
that are meant to crawl inside the human body for medicinal purposes.
Imagine robots that could actually better direct themselves when
entering the human body to deliver treatment or search for sources of
illness!
The applications for this invention are many and they could prove very fruitful for humanity.
Zdroj: web
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Geneticist Says It Could Be Humans That Contaminated Mars With Life
Despite thorough protocols, bacteria or microbes may have survived on the craft sent to Mars by NASA.
In what may be the most surprising news of this week, geneticist Christopher
Mason, a professor at Weill Cornell Medicine, Cornell University, is
now saying that despite NASA's rigorous measures, the agency may have
contaminated Mars with life. The professor wrote an in-depth article
about the subject matter published on the BBC .
In
the feature, Mason asks if any bacteria on Earth could have survived on
the crafts sent to Mars, landed on the planet, and thrived there. These
substances may have then been picked up by Earthly aircraft and considered alien .
"NASA
and its engineers in the Jet Propulsion Laboratory (JPL) have precise
and thorough protocols to minimize the number of organisms that might
inadvertently hitchhike on a space mission. Internationally agreed standards guide how rigorous these protocols should be and NASA meets, and in some cases, exceeds them," writes Mason.
"Yet, two recent studies highlight how some organisms might survive the cleaning process and also the trip to Mars, and also how fast microbial species can evolve while in space ."
Mason
outlines the process that was required to build the Perseverance rover
emphasizing how the rover was built one layer at a time, "like an onion,
with everything cleaned before it is added." These extreme methods are
taken in order to limit the bacteria, viruses, fungi, or spores on
equipment to be sent on a mission.
"But, it is almost impossible to get to zero biomass on
a spacecraft. Microbes have been on Earth for billions of years, and
they are everywhere. They are inside us, on our bodies, and all around
us. Some can sneak through even the cleanest of clean rooms," argues
Mason.
As such, says the scientists, experts must
take measures to ensure any life they find on foreign planets is indeed
of a foreign source. It is quite possible that the life spotted on Mars
could be from an entity that survived on the crafts sent to the Red
Planet.
"But even if Perseverance —
or the missions that preceded it — did accidentally carry organisms or
DNA from Earth to Mars, we have ways of telling it apart from any life
that is truly Martian in origin. Hidden within the DNA sequence will be
information about its provenance," explains Mason.
This
transfer of microbes is not all bad, further explains Mason. In fact,
he argues that when we come to land someday on Mars our microbes will
help us survive there. The key however is to be able to distinguish what
comes from Earth and what comes from the Red Planet.
The Mars Perseverance Rover mission made its way to the Red Planet on July 30, 2020. The Mars 2020 Perseverance is now hunting for microscopic life using a precision X-ray device — called PIXL — powered with artificial intelligence (AI).
Zdroj: web
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Gene Editing: The Future of the Olympics or a Looming Crisis?
Athletes break records every day, constantly raising the bar. Could scientifically perfect athletes be in our future?
The Russian Federation isn’t at the 2020 Tokyo Olympics. Its
athletes aren’t wearing its signature stripes of white, blue, and red,
nor are they carrying its flag. In 2017, the International Olympic
Committee banned Russia from competing in the Olympics. Their charge?
Doping.
After an independent investigation led by the
World Anti-Doping Agency (WADA), investigators found that Russian
officials were doping the country's athletes, providing them with
performance-enhancing drugs that supercharged their elite athletic
abilities. The investigation caused a massive public outcry around the
world and took down a number of athletes who were instrumental to the
nation’s success at the 2014 Winter Olympics at Sochi.
But
what if they hadn’t used performance-enhancing drugs? What if athletes
could turn to more internal changes to amplify their athleticism?
That is the promise – and peril – of gene editing. Genome
editing allows scientists to alter the DNA in an organism, whether
through adding, subtracting, or changing the genetic code at a specific
location. There are many methods for editing DNA, but the most commonly mentioned are CRISPR-Cas9 and TALENs , and the implications for not just the Olympics but all sports deserve serious consideration.
Gene editing methods Two of the inventors of the CRISPR technique,
Jennifer Doudna and Emmanuelle Charpentier, won the Nobel Prize in
Chemistry for its development. CRISPRs, or Clustered Regularly
Interspaced Short Palindromic Repeats, are repeated sequences of DNA
interspersed with unique sequences of spacers. CRISPRs are naturally
occurring— they’re used by bacteria and archaea to fight off pathogens
by slicing up the intruder’s genetic material and adding these slices to
its own genome as a sort of "library". Since the pathogens’ genes
become a part of the bacterium’s genes, the bacteria can “remember” the
pathogen and better fight it in the future.
How did we turn this microbial defense into a gene-editing
powerhouse? It all starts with RNA. The spacer sequences from CRISPR can
be transferred into RNA sequences – the A, C, G, and U. The RNA acts as
a guide, bringing the CRISPR system to a specific spot on the DNA. The
Cas9 enzyme (or other enzymes) are used to bind to this DNA location and
gives it a snip, sending off alarm signals within the cell. The cell
desperately tries to fix the cut DNA, and in doing so pastes the ends
back together, this time without the gene or genes cut off by the
enzyme. The result? Scientists can activate or delete parts of the genes
or sequences of DNA that change some function of the organism.
TALENs ,
or Transcription Activator-Like Effector Nucleases, is another method
being used for efficient gene editing. Xanthomonas genus bacteria wreak
havoc on plants, injecting a protein called TAL that can shut down a
plant's genes. This protein might be bad for plants, but for scientists,
it’s opened up the world of gene editing even more. TAL is made up of
sections that can identify certain DNA nucleotides, and tinkering with
these sections allows scientists to locate genes they want to edit. When
TAL is matched up with endonuclease, which bacteria use to destroy
pathogenic DNA, it creates the TALEN system— TAL protein and
ENdonuclease.
Biology and athleticism During the
Olympics, the physiological prowess of elite athletes is clear, whether
it’s the long-limbed volleyball players or the muscular weightlifters.
Unsurprisingly, physiological advantages vary by sport, but there’s a
number of genetic advantages that can arise.
Lance
Armstrong was considered to be one of the most talented cyclists in
history before his infamous doping scandal. Even without
performance-enhancing drugs, Armstrong still had a genetically powerful
build for cycling: he has a higher maximum oxygen consumption than the
average person. Maximum oxygen consumption, or VO2max, was thought to be
based solely on exercise, but the trainability of VO2max, and VO2max
more broadly, are increasingly associated with genetics .
Michael Phelps, the most decorated Olympian of all time, naturally produces half the lactic acid
of other Olympic swimmers. When we perform high-energy activities, the
body switches from generating energy aerobically (with oxygen) to
generating energy anaerobically (without oxygen). During this process,
the body breaks down a substance called pyruvate into lactic acid. This lactic acid
tires out muscles, leaving them with that all-too-familiar burning
sensation when you exercise. Since Phelps doesn’t have as much lactic
acid, he’s able to recover from high-intensity activity quickly.
In recent years, there’s been major controversy surrounding testosterone and female athletes.
Just recently, Namibian Olympian Christine Mboma was barred from competing in the 400m race on the basis that her testosterone levels were too high . It’s worth noting that testosterone, while it does play a role, may not be the most crucial element in athletic performance.
Many
studies linking an association between the hormone and athleticism are
inherently flawed, as they test the impacts of exogenous testosterone—
in essence, they test the effects of doping rather than naturally
occurring testosterone. Roughly 1 in 4 male Olympians have testosterone
levels that are lower than that present in most men ,
and many of these athletes were competing in sports such as
weightlifting and track, which are often associated with testosterone.
Genetically modifying athletes Here’s the question: could we create designer elite athletes using genome editing? It’s complicated.
In 2018, news broke that twin girls in China were genetically modified
using CRISPR to be born immune to HIV. Conducted by He Jiankui, the
experiment supposedly neutralized the CCR5 gene, which enables HIV to
infect an individual. He Jiankui was subsequently sentenced to three years in prison.
However,
the ethics behind genome editing in humans are hotly contested. The US
National Academy of Sciences and National Academy of Medicine have
hosted an interdisciplinary committee to outline the regulatory
standards and ethics of human gene modification. The very first of these
regulations was that genome editing can occur if it is restricted to preventing the transmission of a serious disease or condition.
The World Anti-Doping Agency recently placed gene editing on their list of prohibited practices and substances .
There’s just one problem— it’s extremely difficult to determine if
someone has modified their genome. One study, however, has shown promise
in alleviating this issue by detecting leftover inactive Cas9
from the CRISPR-Cas9 editing process. However, if an enzyme other than
Cas9 or a different method altogether (like TALEN) is used to edit the
gene, then this method cannot be used.
In theory, we
could genetically engineer children to grow into “better” athletes: a
runner with stronger leg muscles, a taller volleyball or basketball
player, an archer with pinpoint vision. But before we go full-on
Gattaca, it’s worth considering that if every athlete is identical, has
the same strength and flexibility, then what happens to the excitement
of the game?
What
happens to watching, eyes glued to the screen, as the underdog beats
the time-honored pro? Or enjoying the suspense of the world champion
team going up against a lower-seeded rival with something to
prove? Genome editing might not have a role in sports yet, but it begs
the question: if genome editing makes an appearance in sport, would the
joy of the games disappear?
Zdroj: web
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Priceless samples from Ukraine's seed bank destroyed in bomb attack
Part of Ukraine’s national seed bank, a repository of genetic diversity, has been destroyed by a blast in Kharkiv, and the rest of the collection remains at risk.
Tens of thousands of seed samples that were part of Ukraine’s national seed collection have been destroyed by a Russian bomb attack on the city of Kharkiv, according to a video posted on YouTube on 14 May. The collection was the 10th largest in the world and supplied seeds to breeders in many countries, including Russia. “Almost everything turned into ashes,” said Sergey Avramenko at the Plant Production Institute named after V.Ya. Yuriev in the video, which is no longer available. “There were varieties that were hundreds of years old and cannot be restored.” The video shows that the contents of a large room containing bags and packets of seeds have been almost completely destroyed. Only a handful of seeds weren’t burnt black and these probably won’t germinate, said Avramenko. At one point in the video, he showed a puddle of melted metal on the floor. That metal was aluminium, according to Avramenko, meaning temperatures in the room reached at least 660°C. “In these rooms, there was no military or territorial defence, there was only a scientific institution,” he said. Seed banks, also called gene banks, preserve the genetic diversity of plants as a repository for breeders. When the Nazis invaded Ukraine during the second world war, they preserved the seed collection because they recognised its importance, said Avramenko in the video. But Russia deliberately targeted the institute, he claimed. Before the war, the National Gene Bank of Plants of Ukraine in Kharkiv stored more than 150,000 samples of over 1800 plant species from around the world. However, it appears most of these haven’t been destroyed. “Despite recent media reports, our current understanding from the management of the gene bank is that the main seed collections are still safe and that the damage we are seeing online is mainly to an agricultural research station,” Stefan Schmitz, head of the Crop Trust in Bonn, Germany, told New Scientist. “Nevertheless, the main collections of the national gene bank system are at high risk – as are the dedicated staff who maintain them. We are relieved to hear that no lives have been lost among the staff. We are doing what we can to help them,” he says. “The agricultural heritage stored in the Ukrainian gene bank system is of inestimable value not just to Ukrainian agriculture, but to the whole world,” says Schmitz. Seeds can’t be stored indefinitely in seed banks. They have to be resown every few years, with fresh seeds collected and stored, which is why maintaining them is expensive. According to Avramenko, the seeds in the room were those sent out be resown in spring. In another room, he showed that the bicycles staff use to take the seeds to fields had been destroyed. Winter crops were already sown, he says. In 2011, 4 per cent of Ukraine’s seed collection was duplicated and backed up in the Svalbard Global Seed Vault in Norway with the help of the Crop Trust, says Schmitz, and some varieties are also found in seed banks elsewhere. But the vast majority remains at risk. “So if anything is lost, it will be lost forever,” he says. “Any loss of the collections will have a negative impact on prospects for global food and nutritional security. Every seed sample conserved in a gene bank represents a unique additional option available to breeders, researchers and farmers in the fight against climate change and food insecurity, and we cannot afford to lose any of them,” says Schmitz. “We are unfortunately facing an unprecedented loss of agricultural biodiversity in farmers’ fields. We must not lose crop diversity from gene banks too,” he says.
The Plant Production Institute in Kharkiv didn’t respond to a request for comment.
Zdroj: New Scientist
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Genetically engineered bacteria have learned to play tic-tac-toe
Genetically engineered bacteria have learned to play tic-tac-toe E. coli bacteria modified to act like electronic components called memristors can be set up to act as a simple neural network and trained to play noughts and crosses. For the first time, humans have played tic-tac-toe – also known as noughts and crosses – with bacteria. These were no ordinary bacteria, but E. coli extensively genetically modified and set up to act as a simple neural network, a form of artificial intelligence. This approach could have all kinds of applications, from creating living materials capable of learning to making “smart” microbiomes, says Alfonso Jaramillo at the Spanish National Research Council. He and his team started with an E. coli strain genetically modified to sense 12 different chemicals and respond by altering the activity of any genes the researchers chose. This strain, called Marionette, was created in 2019 by another group. Jaramillo and his colleagues further modified the Marionette strain so that it had numerous copies of two bits of circular DNA, called plasmids, each coding for a different fluorescent protein: one red and one green. The ratio of the number of these two plasmids – and hence the colour of the bacteria’s fluorescence – isn’t predetermined and can be altered by the 12 chemicals and by certain antibiotics. In the absence of any further input, this ratio remains constant and is thus a form of memory. What’s more, when the bacteria do get another input, the output – the colour resulting from the ratio of fluorescent proteins – depends on the previous ratio. This means that the bacteria behave in the same way as an electronic component called a memristor that is being used to create computer chips that mimic how the synapses in a brain work. Jaramillo calls these creations “memregulons”. The team decided to teach these memregulons to play tic-tac-toe, as this is a benchmark often used to demonstrate new approaches in computing. The bacteria were grown in eight wells corresponding with the outer squares of a tic-tac-toe grid. For simplicity’s sake, the team assumed that the human player always starts and puts a cross in the centre square. The first bacterial nought is then placed on the square corresponding to the well with the reddest colour. The human plays next and the bacteria are “told” of the move by one of the chemicals they can sense being added to each well – each chemical corresponds to one square. That changes the protein ratio in each well, indicating the next move. Each game takes several days as time is needed for the bacteria to respond. “In the beginning, the bacteria play randomly,” says Jaramillo. But they can be trained by “punishing” wells that play a wrong move with a dose of antibiotics. After eight training games, the bacteria became expert players, says Jaramillo. The team simulated how the trained sets of bacteria play games, and these simulations show they could beat unskilled humans. But the researchers didn’t play any further games after the training stage in which the bacteria lost every time, so E. coli have yet to actually beat humans at tic-tac-toe. “We did not bother to play those winning games,” says Jaramillo. “[It] is a powerful demonstration of adapting a complex biological system to perform an entirely artificial task,” says Joanne Macdonald at the University of the Sunshine Coast in Australia. In 2006, Macdonald created a DNA-based computer that was unbeatable at tic-tac-toe. “The tic-tac-toe game playing with bacteria is an excellent demonstration of their innovative work,” says Sangram Bagh at the Saha Institute of Nuclear Physics in India, who leads one of the two groups that have previously created bacteria-based artificial neural networks. He isn’t convinced that Jaramillo and his team’s set-up meets the definition of an artificial neural network. “But still, it is a good strategy,” says Bagh. Jaramillo says his system is a simple form of neural network known as a one-layer linear artificial neural network. His team is already creating more complex neural networks with the bacteria that can do tasks such as handwriting recognition, he says. “They can do very sophisticated things.”
Zdroj: New Scientist
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All four of the key DNA building blocks have been found in meteorites
We have now discovered all four building blocks of DNA in meteorite
samples, suggesting that space rocks may have delivered the compounds to
Earth, contributing to the origin of life
All four of the key DNA building blocks have now been found in meteorites , suggesting that space rocks may have delivered the compounds to Earth, contributing to the origin of life.
DNA has a spiral-staircase structure, in which each step consists of pairs of molecules called nucleobases .
Two of these four nucleobases – adenine and guanine, which belong to a
group of chemical compounds called purines – were first detected in
meteorites in the 1960s.
Now, Yasuhiro Oba
at Hokkaido University in Japan and his colleagues have discovered the
remaining two DNA nucleobases, cytosine and thymine, known as
pyrimidines, in several meteorites.
The team found the nucleobases in about 2 grams of rock from three
meteorites: the Murchison, Murray and Tagish Lake meteorites. The
Murchison and Murray meteorites, which hit Earth in the mid-20th
century, are thought to date to at least 5 billion years ago. Like
Earth, the Tagish Lake meteorite probably formed 4.5 billion years ago,
and it hit our planet about two decades ago.
Oba’s team ground each rock sample into a powder that was added to
water, before using ultrasound waves to separate the particles into
layers. The group then used mass spectrometry to identify compounds
according to their molecular weight.
“There was a reason why cytosine and thymine in meteorites were never
reported until now … these compounds are in very trace amounts, which
required a method with the capability to measure such small amounts,”
says Michael Callahan at Boise State University in Idaho.
Could the compounds have come from contamination? In soil around the
Murchison meteorite landing site in Australia, the relative amounts of
nucleobases differ substantially from those in the meteorite, suggesting
that the rock’s nucleobases came from space.
“I am convinced that the data is not reflective of terrestrial contamination,” says Bradley De Gregorio at the Naval Research Laboratory in Washington DC.
Rocks containing nucleobases may have hit Earth between 4 and 3.8
billion years ago, in the Late Heavy Bombardment. This precedes the
earliest known undisputed microbe fossils, which are about 3.4 billion
years old.
Oba’s team also detected a higher concentration of nucleobases in the
soil the Murchison meteorite fell onto than in the meteorite.
“If these results are representative of typical pyrimidine
concentrations in meteorites,” says Callahan, “then [nucleobases present
on] Earth would likely have been responsible for the emergence of
genetic material rather than inputs from extraterrestrial delivery.”
Zdroj: New Scientist
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A huge team of scientists finally finishes decoding the last 8% of the human genome
A team of 99 researchers from across the globe published a complete draft of the human genome today in the academic journal Science. The breakthrough comes nearly twenty years after the Human Genome Project made a similar claim by ignoring sections of DNA that were then believed to be unimportant. “The sequence means that we've entered the beginning of a new frontier,” neurogeneticist Erich Jarvis, who is a co-author on the new paper, tells IE. “With complete genomes, I can start to ask new questions of biology that were not possible before,” he says.
This breakthrough was decades in the making The new dataset amounts to an extraordinarily long sequence of just four letters — A, T, C, and G — that represent the four molecules that encode a person’s genes. Unlike the genome unveiled in 2003, today’s announcement includes highly repetitive (but crucially important) regions of the genome that were too difficult for researchers to parse in the 1990s and early 2000s. The full genome is more than three billion letters long. That means that if it were printed in 12-point font, your genetic code would stretch all the way from Houston to Boston. The breakthrough was possible because scientists have better technology and a more refined understanding of genomics than they did two decades ago. It also took a lot of collaboration.
The researchers refined older techniques Almost every cell in the body contains a person’s entire genome, recorded in the exact molecular structure of their DNA. The molecules represented by A, T, C, and G are arranged in a sequence along the length of the DNA. If it were unraveled and stretched out, the DNA contained in a single cell would be roughly eight feet long. Of course, that’s not how DNA exists inside our cells. Evolution has led living things to discover all kinds of innovative ways to fold DNA into a set of packages so small they easily fit inside a cell’s nucleus. Researchers read DNA by chopping it up into pieces that are small enough for existing technology to manage. One reason researchers were able to decipher the complete genome now is that newer machines are able to read longer pieces than they ever have before. Under ideal circumstances, a cutting-edge machine can read DNA fragments that are a few hundred thousand base pairs long. “The DNA is physically going through this pore,” Jarvis says. “As it passes through, the pore reads off the different base pairs.” Researchers don’t read just one copy of DNA. They cultured special cells to produce dozens of identical copies. These are chopped into fragments and read simultaneously. “Imagine your phone is a very thin wafer, filled with millions of pores, and you have the DNA going through all the pores at the same time… you want the same sequence to come through somewhere between 30 to 50 times,” he says. “Then you want to average the information.” Fewer errors helped the researchers assemble the complete genome That redundancy makes it possible to find and fix errors. Not only do errors present a hurdle to scientists who will use this dataset in their research down the line. Errors also add an additional layer of difficulty for the researchers tasked with reassembling the fragments into a complete genome. Commercially available algorithms are able to get roughly 97 or 98 percent of the sequence correct, Jarvis says, “but the remaining two percent still has errors in it.” Those errors present a tremendous challenge when they occur in highly repetitive and “hard-to-sequence regions where it's hard to sort out one copy from another copy.” A member of Jarvis's lab, Giulio Formenti, developed an algorithm that serves as “the last check of sequence accuracy… to clean up the last remaining two percent,” Jarvis says. That contribution — among many others from researchers across the world — made it possible for these researchers to fill in the missing sections of the genome.The researchers plan to sequence a lot more genomes But this is hardly the end of the effort to decode and understand the human genome and its impact on organisms. Bioinformatician Adam Phillippy, a co-leader of the project, says “[t]ruly finishing the human genome sequence was like putting on a new pair of glasses. Now that we can clearly see everything, we are one step closer to understanding what it all means.” Having one complete genome puts us a big step closer to the kind of personalized medicine that researchers have been talking about for decades. "In the future, when someone has their genome sequenced, we will be able to identify all of the variants in their DNA and use that information to better guide their healthcare,” Phillippy says. The new genome is also an important step for researchers who need a complete genome for other reasons. Jarvis is co-leading an effort to sequence hundreds of complete genomes from people around the world. “The goal is to create as complete a human genome as possible, representing much more of human diversity,” he says.
Zdroj: Interesting Engineering
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Rice and maize yields boosted up to 10 per cent by CRISPR gene editing
Turning off a particular gene in maize and rice could enhance grain yields by 10 per cent and 8 per cent respectively, according to a new study. By exploring similar genes in other cereal grains, global crop production could be boosted. Maize and rice are staple foods around the world, and each has a distinct history of cultivation for large-scale consumption. It is believed that maize originated in Mexico, while rice came from China. Despite the independent evolution of these species, plant biologists have noted that they possess some very similar traits. This is known as convergent evolution. To investigate these resemblances, Xiaohong Yang at China Agricultural University in Beijing and her colleagues mapped the genomes of maize (Zea mays L. ssp. mays) and rice (Oryza sativa). They found 490 pairs of genes that seemed to serve analogous functions in both grains. From these pairs, the researchers identified two genes – known as KRN2 in maize and OsKRN2 in rice – that affected their grain yield. By using CRISPR gene editing to switch off these genes, they could increase grain yield by 10 per cent in maize and 8 per cent in rice. These figures came from real-world tests in farm fields. “These are excellent results,” says Yang, who hopes to continue exploring the 490 gene pairs to further improve rice and maize production. “These are two species that are the most important in terms of the economy,” says co-author Alisdair Fernie at the Max Planck Institute of Molecular Plant Physiology in Potsdam, Germany. “They have such different domestication histories with different centres of origin, and very different habitats to a large extent. The fact that convergent evolution happened with so many genes is fascinating.” A better understanding of the genetic evolution of maize and rice could also lead to what are known as de novo domestication events, says Fernie, which is when domesticated genes are inserted into non-domesticated species to make new crops. Wild crops are generally more resilient against extreme weather and pathogens, but typically have a low yield. “With CRISPR and gene editing, we could just take a handful of these domestication genes , such as KRN2, and introduce them back into their wild species relative,” he says. “The idea is that you could make high-yielding but resilient crops, which will be critical for us in the future.”
Zdroj: New Scientist
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Bone-boosting lettuce could help Mars astronauts stay healthy
Eating lettuce containing a hormone that boosts bone formation might help astronauts from losing bone mass in space – and might even help treat osteoporosis on Earth too
Lettuce genetically-modified to produce a bone-forming hormone could
be eaten by astronauts to keep them healthier on long missions.
Bone loss, or osteoporosis, is a common problem when people spend a long time in the microgravity of space .
Astronauts on the International Space Station need to exercise for at
least 2 hours each day and take a bone-preserving drug to limit such
effects. But on longer missions, like a human spaceflight to Mars , stronger bone-forming drugs that require injections could be needed, which would take up valuable cargo space.
Kevin Yates at the
University of California, Davis, and his colleagues used a soil
bacterium to transfer a gene that produces a variant of the human
version of parathyroid hormone (PTH) into lettuce. The same variant is
commonly used as a drug to stimulate bone formation. The researchers
screened a number of modified lettuce plants and observed that the most
productive specimens produced 10 to 12 milligrams of PTH per kilogram.
An astronaut could get all the PTH they need by eating 380 grams of the
lettuce per day.
Yates and his team think that they will be able to improve on the
initial results, which they presented today at the American Chemical
Society Spring 2022 conference in San Diego, California. They hope that
extracting medicine from produce grown from seeds in space could become
the norm for future missions.
“This is a new way of thinking and solving problems for space
exploration,” says Yates. “Typically in the past it’s been abiotic
solutions – just package stuff up and fly it with you or have
consumables that you use up and have more sent to you from Earth.”
Yates also speculates the lettuce could be used to treat osteoporosis
on Earth too, where the condition is seen in millions of people.
“In principle, it could be [useful] in terms of treating osteoporosis,” says David Reid
at the University of Aberdeen, UK. But the use of a hormone that builds
up tissue like PTH might be unnecessary, he adds. “You can usually,
unless it’s very profound, get away with other drugs which prevent bone
breakdown, rather than a bone-forming drug.”
Zdroj: New Scientist
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The patient who got the world's first pig heart transplant has died after 2 months
David Bennett, the
57-year-old man who became globally known as the first human to receive a
genetically modified pig's heart as a transplant has died in the
hospital where he underwent the transplant and was recovering, according
to a press release .
Bennett
was first admitted to the University of Maryland Medical Center (UMMC)
in October last year with arrhythmia - the irregular beating of the
heart, which in his case had become life-threatening. The doctors placed
him on extracorporeal membrane oxygenation (ECMO), commonly known as a
heart-lung bypass machine to keep him alive.
A heart transplant was recommended, but with over 110,000 Americans on the waitlist to receive one, Bennett's time was running out. The clinical team suggested an alternative that had never been tried before.
Xenotransplantation The
only alternative available to Mr. Bennett was a transplant from a
species that wasn't human but a genetically modified pig. Revivicor, a
Virginia-based biotechnology company, uses genetic engineering to
develop a line of pigs that are less likely to be rejected by the human
body. This is because the company has removed genes from the pig that
alarms the human immune system and then put in genes of human origin
that would increase the acceptance of the transplanted organ.
This was the first time, such as transplant was being attempted on a living human being. Earlier in October, the company had transplanted kidneys successfully into a dead body.
Mr.
Bennet was explained all the risks of the procedure and after receiving
special approvals from the U.S. Food and Drug Administration, the
transplant was completed in the first week of January.
The patient was recovering from the surgery Within
days following the surgery, the procedure was hailed as a success since
the organ was not rejected by his body. The transplanted organ was
performing well without any signs of rejection, the hospital noted in
the press release. Bennett wasn't discharged from the hospital after the
surgery and continued to receive recovery care that included physical
therapy to help him regain strength.
Bennett was also
allowed to spend time with his family and even engaged in routine tasks
such as watching Super Bowl during his stay in the hospital. However, a
few days ago, Bennett's health began deteriorating and after the doctors
realized that he would not recover, he was given palliative care. The
exact cause of the death has not been revealed and hospital officials
are expected to conduct a thorough examination to know more, The New York Times reported .
"We
are devastated by the loss of Mr. Bennett. He proved to be a brave and
noble patient who fought all the way to the end. We extend our sincerest
condolences to his family," said Bartley Griffith, one of the surgeons,
who performed the procedure in January. "As with any first-in-the-world
transplant surgery, this one led to valuable insights that will
hopefully inform transplant surgeons to improve outcomes and potentially
provide life-saving benefits to future patients."
Zdroj: Interesting Engineering
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106-million-year-old virus found ‘fossilised’ in the human genome
106-million-year-old virus found ‘fossilised’ in the human genome The remnants of a virus that plagued our mammal ancestors during the age of the dinosaurs have been found lurking in our genomes Around 106 million years ago, the DNA of a virus somehow got integrated into the genome of one of our mammal ancestors. Two million years later, something similar happened again with the same kind of virus. Now, the ancient remnants of that virus has been found inside our cells. “It’s kind of hiding in plain sight in the human genome,” says Aris Katzourakis at the University of Oxford. These two viral “fossils” are some of the oldest ever discovered, and possibly even the oldest. They are also rather unusual. Our genomes are strewn with “fossil” viruses, but almost all are retroviruses, which actively insert DNA copies of their RNA genes into the genomes of the cells they infect. If this happens in cells that give rise to sperm or eggs, this virus-derived DNA can be passed down the generations. Over time, the viral genes mutate and eventually can no longer give rise to infectious viruses. Between 5 and 10 per cent of our genome consists of retroviral remnants. The newly discovered virus instead belongs to an ancient group of DNA viruses called Mavericks. Fossil Mavericks have been found in various animals, including fish, amphibians and reptiles, but until now had never been found in mammals. The researchers think these viruses plagued mammals from the time these animals first evolved around 180 million years ago during the Jurassic Period until at least 105 million years ago during the Cretaceous Period, when the insertions took place. After that, Mavericks appear to have died out in mammals for reasons that aren’t clear. They might still infect other animals, such as fish, but as yet no free-living Maverick viruses have ever been found. “There aren’t that many non-retroviral viruses in our genome,” says Katzourakis. “This is the only DNA virus in the human genome that we know of, and it’s certainly the oldest non-retroviral insertion in our genomes.” There is one fossil retrovirus in the human genome, called ERV-L, that is thought to be older, but there is some overlap in the age estimates. “It is difficult to know for certain whether the ERV-L retrovirus or this Maverick is indeed older as slightly different methodologies were used to ascertain their age,” says Katzourakis.There would have been viral insertions even earlier than these ones, too, but their fossil remnants may have been lost or mutated beyond recognition. Occasionally, though, integrated viral genes are co-opted by evolution and become useful to their hosts.
Zdroj: New Scientist
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106-million-year-old virus found ‘fossilised’ in the human genome
The remnants of a virus that plagued our mammal ancestors during the age of the dinosaurs have been found lurking in our genomes
Around 106 million years ago, the DNA of a virus somehow got integrated into the genome of one of our mammal ancestors. Two million years later, something similar happened again with the same kind of virus. Now, the ancient remnants of that virus has been found inside our cells.
“It’s kind of hiding in plain sight in the human genome,” says Aris Katzourakis at the University of Oxford. These two viral “fossils” are some of the oldest ever discovered, and possibly even the oldest. They are also rather unusual. Our genomes are strewn with “fossil” viruses, but almost all are retroviruses, which actively insert DNA copies of their RNA genes into the genomes of the cells they infect. If this happens in cells that give rise to sperm or eggs, this virus-derived DNA can be passed down the generations. Over time, the viral genes mutate and eventually can no longer give rise to infectious viruses. Between 5 and 10 per cent of our genome consists of retroviral remnants. The newly discovered virus instead belongs to an ancient group of DNA viruses called Mavericks. Fossil Mavericks have been found in various animals, including fish, amphibians and reptiles, but until now had never been found in mammals. The researchers think these viruses plagued mammals from the time these animals first evolved around 180 million years ago during the Jurassic Period until at least 105 million years ago during the Cretaceous Period, when the insertions took place. After that, Mavericks appear to have died out in mammals for reasons that aren’t clear. They might still infect other animals, such as fish, but as yet no free-living Maverick viruses have ever been found. “There aren’t that many non-retroviral viruses in our genome,” says Katzourakis. “This is the only DNA virus in the human genome that we know of, and it’s certainly the oldest non-retroviral insertion in our genomes.” There is one fossil retrovirus in the human genome, called ERV-L, that is thought to be older, but there is some overlap in the age estimates. “It is difficult to know for certain whether the ERV-L retrovirus or this Maverick is indeed older as slightly different methodologies were used to ascertain their age,” says Katzourakis. There would have been viral insertions even earlier than these ones, too, but their fossil remnants may have been lost or mutated beyond recognition. Occasionally, though, integrated viral genes are co-opted by evolution and become useful to their hosts.
Zdroj: New Scientist
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Artificial life made in lab can grow and divide like natural bacteria
SYNTHETIC cells made by combining components of Mycoplasma bacteria with a chemically synthesised genome can grow and divide into cells of uniform shape and size, just like most natural bacterial cells. In 2016, researchers led by Craig Venter at the J. Craig Venter Institute in San Diego, California, announced that they had created synthetic “minimal” cells. The genome in each cell contained just 473 key genes thought to be essential for life. The cells were named JCVI-syn3.0 after the institute and they were able to grow and divide on agar to produce clusters of cells called colonies. But on closer inspection of the dividing cells at the time, Venter and his colleagues noticed that they weren’t splitting uniformly and evenly to produce identical daughter cells as most natural bacteria do. Instead, they were producing daughter cells of bizarre shapes and sizes. “[The creators of JCVI-syn3.0] had thrown out all the parts of the genome that they thought were not essential for growth,” says Elizabeth Strychalski at the US National Institute of Standards and Technology. But their definition of what was necessary for growth turned out to be what was needed to make beautiful colonies growing on an agar plate, she says, rather than what was needed to produce cells that divide in a uniform and lifelike way. By reintroducing various genes into these synthetic bacterial cells and then monitoring how the additions affected cell growth under a microscope, Strychalski and her team were able to pinpoint seven additional genes required to make the cells divide uniformly. When the researchers added these seven genes to JCVI-syn3.0 to produce a new synthetic cell, they found that this was enough to restore normal, uniform cell division and growth. Strychalski and her colleagues found that while two of the seven genes were already known to be involved in cell division, five were previously without a known function. “It was surprising,” she says. “Those five genes were outside the scope of what we had known about,” says James Pelletier at the Massachusetts Institute of Technology, a co-author of the study. “The minimal cell has many genes of unknown function that, although we have no idea what they do, they are necessary for the cell to live – so that’s an exciting area for future research,” he says. “[This research] is incredibly important for understanding how life works and what genes are needed to operate cells reliably,” says Drew Endy at Stanford University in California. “Basic research on minimal cells helps us understand the principles of the phenomena of life, and the evolutionary history of life,” says Kate Adamala at the University of Minnesota in Minneapolis. This is because the minimal cell is a good analogue of the last universal common ancestor of all life on Earth. The new finding also “brings us closer to engineering fully defined, understood and controllable” live cells, she says. “Free of the complexity of natural live systems, synthetic cells are a tool for both basic research and biotechnology.” “The potential applications are vast, in agriculture, nutrition, biomedicine and environmental remediation,” says Jef Boeke at New York University. “The ability to correct and refine biological code like this is a crucial step to getting us there.”
Zdroj: New Scientist
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CRISPR-based 'antibiotic' eliminates dangerous bacterium from the gut
Genetically engineered bacteria armed with CRISPR could help combat antibiotic-resistant infections and also allow doctors to edit people's microbiomes A benign bacterium armed with a designer, CRISPR-based weapon has been used to eliminate a harmful bacterium from the guts of mice while leaving all other microbes unharmed. The approach could give us a new way of tackling antibiotic-resistant infections of the gut and skin, says Sébastien Rodrigue at the University of Sherbrooke in Canada, and also help treat a wide range of diseases by editing the microbiome. Others have shown that this approach works in cells growing in dishes but Rodrigue’s team is the first to get it to work effectively in animals. “And if it works in mice, it should also work in other animals, including people,” he says. CRISPR is best known as a gene-editing tool, but it can also be programmed to kill bacterial cells that have specific bits of DNA inside them. The hard part is that doing this requires getting a CRISPR system inside every single one of the bacterial cells that you want to kill. “The real challenge is the delivery,” says Rodrigue. One way to deliver CRISPR is to exploit circular bits of DNA within bacteria known as conjugative plasmids. These carry genes that make the bacteria pass them on to other bacterial cells via a process called conjugation. Rodrigue’s team tested lots of different conjugative plasmids in a common group of bacteria to find the one that was most effective at transferring itself. The group then evolved it in the lab to make it even more efficient. The team added the genes for a CRISPR system targeting an antibiotic-resistant strain of E. coli, and put the plasmid inside a benign bacterium used as a probiotic. When the CRISPR-armed probiotic bacteria were given to mice, they eliminated 99.9 per cent of the E. coli bacteria in four days. Next, the team targeted a bacterium called Citrobacter rodentium that damages the guts of mice it infects. The CRISPR-armed probiotic bacteria cured infections within four days. “It completely eliminated the Citrobacter rodentium,” says Rodrigue. The team has now begun testing the method in pigs, where it could provide an alternative to the antibiotics widely used by farmers. The method is very efficient, says Alejandro Chavez at Columbia University in New York. “Overall, an approach like this is certainly possible.” But there are potential risks with such efficient conjugative plasmids, says Chavez. If something went wrong, the plasmids might end up spreading undesirable genes. To ensure nothing like this can happen, Rodrigue plans to ensure that the plasmids don’t persist after treatment. One way to do this is to delete the genes that the plasmids need to replicate, so they soon die out. Another is to make the CRISPR system target and destroy the plasmids after a certain delay – a timed self-destruct system. “That’s the next step in terms of biocontainment,” says Rodrigue. The CRISPR-armed probiotic bacteria effectively act as a highly selective antibiotic. They could be used to treat infections wherever bacteria can survive in the body, from the skin to the bladder. In addition, many medical conditions, from cancer to Crohn’s, are associated with changes in people’s microbiome, says Rodrigue. It often isn’t clear where these changes are a cause or a consequence. Having a tool that allows us to alter the microbiome will help us find out, and could lead to new treatments. “We could use this as a way of changing the microbiome to favour health rather than disease,” says Rodrigue.
Zdroj: New Scientist
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CRISPR-based 'antibiotic' eliminates dangerous bacterium from the gut
Genetically engineered bacteria armed with CRISPR could help combat antibiotic-resistant infections and also allow doctors to edit people's microbiomes A benign bacterium armed with a designer, CRISPR-based weapon has been used to eliminate a harmful bacterium from the guts of mice while leaving all other microbes unharmed. The approach could give us a new way of tackling antibiotic-resistant infections of the gut and skin, says Sébastien Rodrigue at the University of Sherbrooke in Canada, and also help treat a wide range of diseases by editing the microbiome. Others have shown that this approach works in cells growing in dishes but Rodrigue’s team is the first to get it to work effectively in animals. “And if it works in mice, it should also work in other animals, including people,” he says. CRISPR is best known as a gene-editing tool, but it can also be programmed to kill bacterial cells that have specific bits of DNA inside them. The hard part is that doing this requires getting a CRISPR system inside every single one of the bacterial cells that you want to kill. “The real challenge is the delivery,” says Rodrigue. One way to deliver CRISPR is to exploit circular bits of DNA within bacteria known as conjugative plasmids. These carry genes that make the bacteria pass them on to other bacterial cells via a process called conjugation. Rodrigue’s team tested lots of different conjugative plasmids in a common group of bacteria to find the one that was most effective at transferring itself. The group then evolved it in the lab to make it even more efficient. The team added the genes for a CRISPR system targeting an antibiotic-resistant strain of E. coli, and put the plasmid inside a benign bacterium used as a probiotic. When the CRISPR-armed probiotic bacteria were given to mice, they eliminated 99.9 per cent of the E. coli bacteria in four days. Next, the team targeted a bacterium called Citrobacter rodentium that damages the guts of mice it infects. The CRISPR-armed probiotic bacteria cured infections within four days. “It completely eliminated the Citrobacter rodentium,” says Rodrigue. The team has now begun testing the method in pigs, where it could provide an alternative to the antibiotics widely used by farmers. The method is very efficient, says Alejandro Chavez at Columbia University in New York. “Overall, an approach like this is certainly possible.” But there are potential risks with such efficient conjugative plasmids, says Chavez. If something went wrong, the plasmids might end up spreading undesirable genes. To ensure nothing like this can happen, Rodrigue plans to ensure that the plasmids don’t persist after treatment. One way to do this is to delete the genes that the plasmids need to replicate, so they soon die out. Another is to make the CRISPR system target and destroy the plasmids after a certain delay – a timed self-destruct system. “That’s the next step in terms of biocontainment,” says Rodrigue. The CRISPR-armed probiotic bacteria effectively act as a highly selective antibiotic. They could be used to treat infections wherever bacteria can survive in the body, from the skin to the bladder. In addition, many medical conditions, from cancer to Crohn’s, are associated with changes in people’s microbiome, says Rodrigue. It often isn’t clear where these changes are a cause or a consequence. Having a tool that allows us to alter the microbiome will help us find out, and could lead to new treatments. “We could use this as a way of changing the microbiome to favour health rather than disease,” says Rodrigue.
Zdroj: New Scientist
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DNA of Native American leader Sitting Bull matched to living relative
Tatanka Iyotake, popularly known as Sitting Bull, is famed as a 19th century leader of the Hunkpapa Lakota Sioux people – and DNA strengthens the claim that he has living descendants A study that blends history with contemporary DNA technology has further strengthened the claim of a familial relationship between a living Native American and a historical figure: Tatanka Iyotake, popularly known as Sitting Bull. Sitting Bull was a leader of the Hunkpapa Lakota Sioux people. In 1876, he was victorious against General Custer’s 7th Cavalry Regiment of the US Army in the Battle of the Little Bighorn, also known as the Battle of the Greasy Grass. Today, Ernie LaPointe, a Native American author and president of the Sitting Bull Family Foundation, is widely accepted as the great-grandson of Sitting Bull. Now, LaPointe has had his claim strengthened by genetics . LaPointe and his three sisters have previously used historical records, including birth and death certificates, to make a strong case of a familial relationship with Sitting Bull. In 2007, a lock of Sitting Bull’s hair that had been preserved at the National Museum of Natural History in Washington DC was repatriated to LaPointe and his sisters – and a small sample was sent to a team of geneticists led by Eske Willerslev at the University of Copenhagen to allow for DNA analysis . The outcome of the analysis was important for LaPointe, who is named as a co-author on the new study. In order to secure the right to determine the fate of the final resting place of Sitting Bull, he needed to provide irrefutable evidence that Sitting Bull was indeed his forbear. Genetic evidence would serve this purpose. By comparing DNA from Sitting Bull’s hair with DNA from LaPointe’s saliva, the new study does indeed irrefutably establish that LaPointe is the great-grandson of the legendary leader, says Willerslev. Willerslev says the methods generally used to establish ancestry, such as analysis of the Y chromosome, weren’t possible in this case because the DNA in the hair sample was so degraded. But it was possible to use haplotype frequency to establish a relationship. A haplotype is a set of alleles inherited from one parent. Even unrelated individuals can share common haplotypes, so Willerslev’s team took saliva samples from non-related members of LaPointe’s community, to detect haplotypes that were specific to Sitting Bull’s bloodline. “It’s fair to say that the more material you have… the more reliable your results will be,” says Willerslev, but he is still confident that the genetic evidence is incontrovertible. Willerslev, who has been fascinated by Sitting Bull and his legacy since childhood, attended a traditional Lakota ceremony where Sitting Bull’s spirit was resurrected to obtain permission to use the reclaimed lock of hair for scientific scrutiny. Oglala Lakota Nation President Kevin Killer, a Lakota Sioux Native American leader, explains that hair has a special significance in Native American culture and is considered sacred and the seat of the spirit. Killer, who wasn’t involved in the study, welcomes the research, which lends support to the culture of oral history of Indigenous people. “To see [our oral history] backed up by science… is a step in proving how strong our oral history that dates back to 10,000 years [is].” Kimberly TallBear-Dauphine at the University of Alberta in Canada, a Dakota Native American who wasn’t involved in the study, says that LaPointe’s descent from Sitting Bull was never really contested since Lakota people’s genealogies are very well documented both through paper documentation and oral history. “I’m sure there are benefits for scientists in the use of this technology… [but] they are simply confirming genetically what we already knew through other kinds of evidence,” she says. Putting the study in perspective, she says: “It certainly doesn’t give Lakota people anything they didn’t already know in terms of Ernie’s relationship with Sitting Bull.”
Zdroj: New Scientist
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Genetically engineered bacteria could heal us from inside our cells
Billions of years ago, bacteria began living inside other cells and carrying out essential functions. Genetic engineering could create new types of these ‘endosymbionts’ Bacteria have been genetically engineered to enter and live inside mouse immune cells, where they released proteins that altered the behaviour of those cells. The work is a first step towards creating “artificial endosymbionts” that could live inside some human body cells and do everything from guiding the regeneration of damaged tissues to treating cancer. “That’s the vision in the long run,” says Christopher Contag at Michigan State University. Several other groups are also developing artificial endosymbionts, which they say could allow us to make crops and farm animals more productive, and could treat age-related conditions. The idea of creating artificial endosymbionts used to be regarded as fanciful, says Bogumil Karas at the University of Western Ontario in Canada, but due to the huge advances in our ability to engineer organisms in recent years, it is starting to be seen as feasible. “This is going to be one of the biggest things in the very near future,” he says. “I’ve seen huge interest in the last five years or so.” Most organisms depend on the microbes living on or in them – the microbiome – but sometimes the relationship is even more intimate. Some bacteria live inside the cells of plants or animals in a mutually beneficial relationship called endosymbiosis. Endosymbionts can give organisms abilities vital for their survival. The energy-producing structures in all animal and plant cells evolved from endosymbiotic bacteria, as did the photosynthetic structures in all plant cells. To create a new endosymbiont from scratch, Contag’s team started with a bacterium called Bacillus subtilis, found in our guts among other places. “It’s a normal microbiome bacterium,” says team member Cody Madsen, also at Michigan State University. The researchers engineered it to produce mammalian proteins that alter the activity of genes and thus control what mammalian cells do. To get the bacteria inside mouse cells, Contag and Madsen and their colleagues relied on the fact that some animal cells can engulf bacteria via a process called phagocytosis. Normally, engulfed bacteria remain trapped in membrane-bound sacs where they are digested. But the engineered B. subtilis strain secretes a protein that enables it to break out of these sacs. The researchers added the engineered bacteria to mouse immune cells known as macrophages growing in a dish. They managed to get the bacteria into 99 per cent of cells. They also showed that the mammalian proteins the bacteria had been engineered to produce altered the behaviour of the macrophages. What the team has yet to achieve is getting the bacteria to live in harmony with their new hosts. After two days, 10 per cent of the macrophages were killed by the bacteria inside them, which divided and reproduced too fast. The next step, says Madsen, is to add a genetic circuit that will ensure the bacteria divide only when the host cell divides. The team also plans to engineer the bacteria so they can be controlled once they are inside an animal, by making them respond to specific chemicals or magnetic fields. The advantage of using magnetism is that it would give localised control. “You could make the cells that have these endosymbionts into stem cells, and then flip another switch and turn that stem cell into another cell type,” says Contag. Such switches could also be used to kill off the bacteria if necessary, says Madsen. It is amazing the team managed to get the bacteria into such a high proportion of cells, say Karas. But achieving this in the body, and in other cell types, will be much more difficult, he says, and getting long-term survival is obviously crucial. “I’m not convinced that engineered endosymbionts would necessarily offer advantages beyond less complex approaches,” says John Rasko, a stem cell expert at the University of Sydney. “The regulatory hurdles and ethical challenges are probably even greater than the technical ones.” There are many other ways to control gene activity in mammalian cells, says Huseyin Sumer at the Swinburne University of Technology in Australia. “The most immediate application [of artificial endosymbionts] could be in agriculture,” he says. For instance, plants such as beans don’t need nitrogen fertilisers because they can capture nitrogen directly from the atmosphere with the help of bacteria growing on their roots. Karas’s team is trying to give other crops this ability by turning the nitrogen-fixing bacteria into endosymbionts. This could have enormous benefits, as nitrogen fertilisers are a large source of greenhouse gases as well as a major pollutant of rivers and seas. In principle, artificial endosymbionts could be used to give animals some extraordinary abilities. Sumer says his team had begun experiments to see if mammalian cells could be made to photosynthesise before the pandemic interrupted the work.
Zdroj: New Scientist
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Genetically engineered bacteria could heal us from inside our cells
Billions of years ago, bacteria began living inside other cells and carrying out essential functions. Genetic engineering could create new types of these ‘endosymbionts’
Bacteria have been genetically engineered to enter and live inside mouse immune cells, where they released proteins that altered the behaviour of those cells. The work is a first step towards creating “artificial endosymbionts” that could live inside some human body cells and do everything from guiding the regeneration of damaged tissues to treating cancer.
“That’s the vision in the long run,” says Christopher Contag at Michigan State University.
Several other groups are also developing artificial endosymbionts, which they say could allow us to make crops and farm animals more productive, and could treat age-related conditions.
The idea of creating artificial endosymbionts used to be regarded as fanciful, says Bogumil Karas at the University of Western Ontario in Canada, but due to the huge advances in our ability to engineer organisms in recent years, it is starting to be seen as feasible.
“This is going to be one of the biggest things in the very near future,” he says. “I’ve seen huge interest in the last five years or so.”
Most organisms depend on the microbes living on or in them – the microbiome – but sometimes the relationship is even more intimate. Some bacteria live inside the cells of plants or animals in a mutually beneficial relationship called endosymbiosis.
Endosymbionts can give organisms abilities vital for their survival . The energy-producing structures in all animal and plant cells evolved from endosymbiotic bacteria , as did the photosynthetic structures in all plant cells.
To create a new endosymbiont from scratch, Contag’s team started with a bacterium called Bacillus subtilis , found in our guts among other places. “It’s a normal microbiome bacterium,” says team member Cody Madsen, also at Michigan State University.
The researchers engineered it to produce mammalian proteins that alter the activity of genes and thus control what mammalian cells do.
To get the bacteria inside mouse cells, Contag and Madsen and their colleagues relied on the fact that some animal cells can engulf bacteria via a process called phagocytosis . Normally, engulfed bacteria remain trapped in membrane-bound sacs where they are digested . But the engineered B. subtilis strain secretes a protein that enables it to break out of these sacs.
The researchers added the engineered bacteria to mouse immune cells known as macrophages growing in a dish. They managed to get the bacteria into 99 per cent of cells. They also showed that the mammalian proteins the bacteria had been engineered to produce altered the behaviour of the macrophages .
What the team has yet to achieve is getting the bacteria to live in harmony with their new hosts. After two days, 10 per cent of the macrophages were killed by the bacteria inside them, which divided and reproduced too fast.
The next step, says Madsen, is to add a genetic circuit that will ensure the bacteria divide only when the host cell divides.
The team also plans to engineer the bacteria so they can be controlled once they are inside an animal, by making them respond to specific chemicals or magnetic fields. The advantage of using magnetism is that it would give localised control.
“You could make the cells that have these endosymbionts into stem cells, and then flip another switch and turn that stem cell into another cell type,” says Contag.
Such switches could also be used to kill off the bacteria if necessary, says Madsen.
It is amazing the team managed to get the bacteria into such a high proportion of cells, say Karas. But achieving this in the body, and in other cell types, will be much more difficult, he says, and getting long-term survival is obviously crucial.
“I’m not convinced that engineered endosymbionts would necessarily offer advantages beyond less complex approaches,” says John Rasko , a stem cell expert at the University of Sydney. “The regulatory hurdles and ethical challenges are probably even greater than the technical ones.”
There are many other ways to control gene activity in mammalian cells, says Huseyin Sumer at the Swinburne University of Technology in Australia. “The most immediate application [of artificial endosymbionts] could be in agriculture,” he says.
For instance, plants such as beans don’t need nitrogen fertilisers because they can capture nitrogen directly from the atmosphere with the help of bacteria growing on their roots . Karas’s team is trying to give other crops this ability by turning the nitrogen-fixing bacteria into endosymbionts.
This could have enormous benefits, as nitrogen fertilisers are a large source of greenhouse gases as well as a major pollutant of rivers and seas.
In principle, artificial endosymbionts could be used to give animals some extraordinary abilities. Sumer says his team had begun experiments to see if mammalian cells could be made to photosynthesise before the pandemic interrupted the work.
Zdroj: New Scientist
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IVF embryos discarded as 'abnormal' can actually become healthy babies
Embryos that are often discarded by IVF clinics because they contain some seemingly abnormal cells are just as likely to develop into healthy babies as embryos with no chromosomal abnormalities, two new studies show.
The finding means that many people trying to conceive with IVF will have more embryos to choose from and can worry less about using slightly abnormal ones.
To select the most viable embryos for implantation, IVF clinics visually assess their shape and structure and often do genetic tests as well. This pre-implantation genetic testing is useful for identifying embryos with major chromosomal abnormalities that are unlikely to survive, but there is controversy over what to do with those that only contain a small portion of cells with chromosomal abnormalities – known as mosaic embryos.
About 1 in 4 embryos made via IVF are found to be mosaic. These embryos are often discarded or used as last-ditch options because of the perceived risks that they will miscarry or develop into babies with chromosomal conditions.
However, two studies that will be presented at the annual meeting of the American Society for Reproductive Medicine on 20 October in Baltimore, Maryland, suggest these concerns are unfounded.
In the first study, Andria Besser at New York University Langone Fertility Center and her colleagues monitored the pregnancies of 35 people who had been implanted with mosaic embryos. Testing at the end of the first trimester showed that none of their fetuses had chromosomal abnormalities .
In the second study, Antonio Capalbo at Igenomix, a global reproductive genetic testing company, compared pregnancy outcomes for 484 chromosomally normal embryos, 282 low-level mosaic embryos and 131 moderate-level mosaic embryos made via IVF. Mosaicism was classified as low level if 20 to 30 per cent of cells in the embryo had abnormal numbers of chromosomes and moderate if this figure was 30 to 50 per cent.
Both types of mosaic embryos had the same chance of implanting as chromosomally normal embryos and had the same chance – about 42 per cent – of leading to the successful births of babies. Genetic testing of the newborns found they had no chromosomal abnormalities , regardless of what kind of embryo they came from.
There could be two reasons for these findings. One is that mosaic embryos may have ways of removing abnormal cells as they develop. The other, which both Besser and Capalbo believe is more likely, is that testing difficulties lead to many embryos being identified as mosaic when they aren’t. Embryo testing is tricky because it involves sampling tiny amounts of DNA from the layer of cells surrounding the embryo, which are hard to analyse and may not reflect the chromosomal status of the embryo itself.
“But in any case, there doesn’t seem to be any negative outcomes associated with the transfer of these embryos,” says Capalbo.
The findings are consistent with recent work by Nathan Treff and Diego Marin at US reproductive testing company Genomic Prediction, who reviewed the outcomes of more than 2700 mosaic IVF embryo transfers and found that only one resulted in a child with mosaicism. This mosaicism was mild and didn’t affect the child’s health.
Our new understanding of mosaic embryo outcomes could spare IVF clients a lot of unnecessary heartache and worry, says Capalbo. Surveys have found that two-thirds of IVF clients who only have mosaic embryos decide not to use them , probably because of the perceived risks, and more than a third of IVF clinics in the US wouldn’t implant mosaic embryos .
“We’re definitely seeing a shift now in thinking about mosaic embryos,” says Besser. “Everyone used to be really nervous about transferring them because we just didn’t know the risks, but now we have this data to back us up, we can provide much more reassurance to people.”
Zdroj: New Scientist
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Scientists Use Gene Therapy to Restore Vision After Stroke in Mice
Researchers from the Purdue Institute for Integrative
Neuroscience, Pennsylvania State University, and Jinan University in
China have collaborated on a study to restore vision after stroke in
mice using gene therapy, a press release from Purdue University said.
A stroke is a medical condition
when an artery in the brain is blocked preventing tissues in the area
from getting oxygen and nutrients. The oxygen-starved cells die leading
to a loss of function. On most occasions, a stroke patient loses the
ability to move a part of his body but in many cases, it affects their
vision too.
The neuronal network is flexible though and can sometimes
repair itself to restore vision in stroke patients. In the past,
scientists have attempted stem cell therapy to restore vision but a
patient’s immune system can reject these treatments due to immune
mismatches. Professor Alexander Chubykin is an expert on neurons and
under his guidance, the team decided to use gene therapy instead.
Previous research has shown that a transcription factor,
NeuroD1, can activate certain genes that can convert astrocytes into
neurons. Astrocytes are cells in the brain and spinal cord that do not
carry electrical impulses but protect the neurons – the cells that carry
electrical impulses and provide them oxygen and nutrients. Using
NeuroD1-mediated gene therapy , these supporting cells can be converted into important information-carrying cells.
The researchers first induced stroke in mice so that it
affected the visual centers in the brain and then measured the extent of
the vision loss. They then delivered the gene therapy into the affected
areas and allowed the transformed cells to be integrated into neural
pathways, restoring vision loss.
“We don’t have to implant new cells, so there’s no immunogenic
rejection. This process is easier to do than stem cell therapy, and
there’s less damage to the brain,” said Chubykin in a press release. “We
can see the connections between the old neurons and the newly
reprogrammed neurons get reestablished. We can watch the mice get their
vision back.”
The team also measured the responses to a visual stimulus after the intervention and the extent of recovery in the mice. The study published in Frontiers journal
states that after therapy, the neurons in the mice regained normal
levels of response to light in as little as three weeks. Further
research in this area can be used to correcting the loss of motor
function in the future, the press release said.
Zdroj: Interesting Engineering
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How our ape ancestors suddenly lost their tails 25 million years ago
Around 25 million years ago, our ancestors lost their tails. Now
geneticists may have found the exact mutation that prevents apes like us
growing tails – and if they are right, this loss happened suddenly
rather than tails gradually shrinking.
“You lose the tail in one fell swoop,” says Itai Yanai at NYU Langone Health in New York.
His colleague Bo Xia says
he used to wonder as a child why people didn’t have tails like other
animals. “This question was in my head when I was a little kid,” he
says. “I was asking, ‘Where is my tail?’.”
More recently, Xia’s coccyx – a small bit of bone at the base of the
spine that is a vestige of mammalian tails – was injured in a car
accident. “It was really painful,” he says. “It kept reminding me about
the tail part of our body.”
That led Xia to investigate the genetic basis
of tail loss. Any mutations involved in tail loss should be present in
apes but not monkeys. He and his colleagues compared ape and monkey
versions of 31 genes involved in tail development.
They found nothing in the protein-coding regions, so they looked in the bits of junk DNA
found inside genes. If you think of proteins as flat-pack furniture,
the genetic instruction booklets for making them come with lots of pages
of gibberish that have to be removed before the instructions work.
These extra bits, called introns, are cut from the mRNA copies of genes
before proteins are made.
What Xia found is that in the ancestor of apes, in a tail gene called TBXT , an Alu element landed smack bang in the middle of an intron. Alu elements are genetic parasites that copy and paste themselves all over the genome. “We have 1 million Alu elements littering our genome,” says Yanai.
Normally, an Alu in an intron would make no difference – it would get edited out with the intron . But in this case, there is another Alu
element nearby, but it is in inverse order. Because the two sequences
are complementary, Xia realised, they bind together, forming a loop in
the mRNA.
That effectively glues several pages of the instruction booklet
together, meaning that when the extra pages are cut out, some of the
instructions are often lost too. This means the assembled furniture –
the TBXT protein – often has a key piece missing.
The team did several experiments to demonstrate this. For instance,
they showed that mice with this mutation produce a mixture of
full-length and missing-bit TBXT proteins – like apes do – and that this
usually results in complete tail loss.
“For something to be lost in one big burst is really significant,
because you don’t then have to posit millions of years of successive
tiny changes accumulating gradually,” says Carol Ward
at the University of Missouri. “It may tell us why all of a sudden when
we see the apes [emerge] they have no tails,” she says. While there’s
no evidence of a slow reduction in tail length in the fossil record,
says Ward, for now we have too few fossils to rule it out.
What the finding cannot tell us is why our ancestors lost their
tails; that is, why this mutation was selected for by evolution. Most
proposed explanations involve tails being a disadvantage when early apes
started moving in a different way, such as walking upright on branches. But fossils suggest the first tail-less apes still walked on all fours, says Ward.
Xia and Yanai think there must have been a strong advantage to losing
tails because this mutation does also have a disadvantage. Some mice
developed spinal abnormalities resembling spina bifida. They speculate
that the relatively high rate of spina bifida in people is a lingering
relic of the loss of our tails all those millions of years ago.
Zdroj: New Scientist
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It’s now easier to run trials testing CRISPR-edited crops in England
Law changes later this year will make it easier to run field trials
in England on crops that are gene-edited for environmental and
nutritional benefits.
The UK government, which announced the move today, also said it plans
future legislation so gene-edited crops and livestock that mimic the
effects of natural breeding are treated differently to genetically
modified (GM) ones, a step that would pave the way to gene-edited food
being sold in UK supermarkets for the first time.
Gene editing sees the DNA of an organism precision-targeted, often using CRISPR
technology. This means gene editing doesn’t involve inserting whole
genes or genes from other species, which other GM crops may carry. A
recent example tested in the real-world involved wheat edited to lower the risk of a carcinogenic compound forming when bread made from the wheat is toasted.
Proponents say such edited crops simply speed up natural breeding
techniques, and could bring environmental benefits such as reducing
pesticide use by developing blight-resistant potatoes.
The UK approach signals a post-Brexit divergence from the European Union, which regulates gene-edited organisms in the same way as GM ones , effectively banning them from being grown and sold. The UK carried over that regulation when it left the EU.
Today’s first step away from that regulation is a modest one following a consultation .
The government will lift the licensing hurdles that laboratories face
when starting a field trial of gene-edited crops, a crucial exercise to
see how well they grow in more realistic conditions.
The change in England, to be undertaken using secondary legislation
before the year is out, should save about £10,000 per trial and cut a
two month wait before trials can begin.
Wendy Harwood
at the John Innes Centre in Norwich, UK, says: “We’re hoping it will
make it easier to have a look at these plants in the field, which will
enable scientists to identify which ones to take forward.”
However, researchers will still have to notify the Department for
Environment, Food and Rural Affairs, and Scotland and the rest of the UK
may decide different rules. The UK government believes the rule changes
are less important than the statement of intent they send, to unlock
investment in gene-edited crops.
“It’s vitally important. It applies to research and development only, but it’s a first step,” says Nigel Halford
at Rothamsted Research, UK, which is trialling gene-edited wheat. “If
you’re going to get investment from plant breeders in the technology,
they have to be confident their products will have a market.”
Today’s rule changes won’t allow “authorisation” for gene-edited food
to be sold. Yet that may change too. The UK government said it plans a
longer-term review of GM regulation, which would see primary legislation
to change the definition of GM organisms to exempt gene-edited crops –
and livestock too – if they could have been developed by traditional
breeding. That could apply to the whole of the UK. Whether products
would have to be labelled as gene-edited remains to be decided.
The government may face an uphill battle on public attitudes, and it
is unknown whether they will be on a par with the outcry two decades ago
where protesters ripped up trials of GM crops, and opponents branded
them “Frankenfoods”. Among the 6440 responses to a new consultation, 88
per cent of individuals and 64 per cent of businesses said they believed
gene-edited crops should continue to be regulated as GM organisms.
So what happens next? “It has to be small steps,” says Harwood. “Food safety is paramount.”
Gene-edited food is already sold in some countries including the US, and this month saw the launch of tomatoes in Japan
that appear to be the first food altered by CRISPR, a newer technique
than that used in the US products. The EU is also mulling a rethink on
its stance towards gene-edited crops, with a review launched in April calling the existing rules “not fit for purpose”, because the regulations predate the development of CRISPR technology.
The UK may end up a bit ahead, says Harwood. “The technology has
moved on so far and the regulations just need to catch up.” She expects
UK staple crops such as cereals, wheat, barley, brassicas and potatoes
to be future candidates for gene-edited crops but says regulatory
changes mean we are unlikely to be eating them soon. “We are probably
looking at a few years before we see these products on the shelves,” she
says.
Zdroj: New Scientist
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A 'Gene Silencing' Injection Was Just Approved for Use in Humans
A new method is nearing a critical development threshold.
The
United Kingdom's NHS approved a new cholesterol-reducing shot that will
be provided to 300,000 people throughout the next three years,
according to a press release from the U.K. agency .
Crucially, this marks the first use for a novel new therapeutic called "gene silencing" to treat common illnesses.
The new gene-silencing drug targets mRNA to reduce cholesterol levels Called
inclisiran, the new drug will be injected twice yearly, primarily for
patients suffering from a genetic condition linked to high cholesterol,
people who've had a stroke or heart attack, or those who have negative
or underwhelming reactions to cholesterol-reducing drugs ,
like statins. This drug has become the object of much anticipation, not
only because it has great potential, but also because it employs a
novel technique called "gene slicing". This emerging therapeutic
technique specifically targets the underlying causes of disease, instead
of the symptoms one experiences when it takes effect. This works by
selecting a specific gene and stopping it from producing the protein
responsible for the illness.
Until this new drug, gene
silencing technology was typically only used for rare genetic diseases,
which makes the forthcoming cholesterol shot the first of its kind to
treat people for more common health problems, and on an unprecedented
scale. For example, researchers are presently considering how gene
silencing might help the treatment of several other health conditions ,
like cancer, or Alzheimer's disease. But it won't be easy. Gene
silencing drugs target a precise kind of ribonucleic acid (RNA) in the
human body, known as "messenger" RNA (mRNA). Every cell in your body has
RNAs, where they perform a crucial role in the passage of genetic
information. Additionally, mRNA is one of the most important kinds of
RNA in the body, since it copies and transports genetic instructions,
and produces proteins according to instructions.
Non-viral vectors could be key to repeat doses of gene silencing The
new cholesterol jab employs gene silencing via a protein known as
PCSK9, which it degrades. This specific protein is used to regulate
cholesterol in the human body, but it exists with excess frequency in
people experiencing high levels of LDL cholesterol, which is the bad
kind. By stopping this protein from production, cholesterol levels will
naturally drop. But to target this mRNA, researchers have to build a
synthetic version of a different type of RNA known as interfering RNA
(siRNA). It's a highly localized span of RNA that enables the precise
targeting of individual mRNAs. And, in the case of the new drug, the
siRNA was forged to target the mRNA known for carrying instructions
intended for the PCSK9 protein.
It then binds to the
target mRNA, and obliterates these instructions, substantially reducing
the amount of proteins produced. Conventionally, gene therapies are
employed via specific viral vectors, which are virus-like vehicles
capable of moving genes to cells just like a virus would. As of writing,
viral vector therapies have seen use in treating genetic blindness,
genetic blood disorders, and spinal muscular atrophy. These are highly
effective during the first treatment, but it could be impossible to
deliver a second dose via the same method, should negative immune
reactions occur. They're also expensive, which is why scientists are
also investigating non-viral vector gene therapies that use a
nanoparticle capable of preserving the drug from blood-based
degradation, saving it for the target, for example, in the liver. While
promising, for now, these gene silencing techniques must prove effective in forthcoming trials, before they may be applied on even wider scales.
Zdroj: New Scientist
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mRNA cancer therapy now in human trials after shrinking mouse tumours
A cancer treatment that uses messenger RNA to launch an immune attack
on cancer cells can completely shrink tumours in mice and is now being
tested in people.
Messenger RNAs – or mRNAs – are molecules that instruct cells to make proteins. They have risen to fame with the roll out of mRNA covid-19 vaccines .
BioNTech , the German company that developed Pfizer’s mRNA covid-19 vaccine , is now testing whether mRNAs can be used to treat cancer by stimulating cells to produce tumour-fighting proteins.
The company made a mixture of four mRNAs that instruct cells to
produce four proteins called cytokines that are naturally released by
immune cells to attack cancer cells.
When they injected these mRNAs directly into melanomas in 20 mice,
immune cells within the tumours began producing large amounts of the
desired cytokines. This produced an immune response that caused the skin
tumours to completely disappear in all but one of the mice in less than
40 days.
In another experiment, mice that had melanomas as well as lung
tumours were treated with the mRNA mixture. The mRNAs were only injected
into the melanomas, but they also suppressed the growth of the lung
tumours. This may be because the immune cells activated by the mRNAs
were able migrate to the distant tumours, says Timothy Wagenaar at Sanofi, a pharmaceutical company that is partnering with BioNTech to develop the treatment.
The mice didn’t display any side effects and didn’t lose weight during the treatment.
Following these promising results, BioNTech and Sanofi are now
testing the safety of the mRNA mixture in 231 people with advanced
melanoma, breast cancer and other solid tumours. They presented
preliminary results of the first 17 patients
at the Society for Immunotherapy of Cancer annual meeting in November
2020, showing they had no serious side effects. Future trials will test
how well the therapy works.
For now, the treatment is only suitable for tumours that are near the
surface of the body, since the mRNAs must be directly injected into the
tumours. But in future, it may be possible to use ultrasound or other
imaging techniques to guide injections into deeper tumours, says
Wagenaar.
Zdroj: New Scientist
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Humans reached Arabia in at least five waves thanks to wetter climates
Ancient humans repeatedly entered the Arabian peninsula from Africa
during the past 400,000 years. A single archaeological site in Saudi
Arabia holds evidence of five separate occupations, according to a new
study.
A second study suggests that each out-of-Africa migration was made
possible by a shift to a wetter climate, creating green corridors. It
simulated changes in the region’s climate over the past 300,000 years,
and found that there were several periods when conditions were ideal for
people to move from Africa to Asia.
“It just establishes how closely early human migrations were linked to climate change,” says Huw Groucutt at the Max Planck Institute for Chemical Ecology in Jena, Germany.
Groucutt and his colleagues excavated a site called Khall Amayshan-4
in the Nefud desert in what is now northern Saudi Arabia. In a single
hollow between sand dunes, the team found the preserved remains of
several lakes that had formed during spells of wetter climate and then
dried up.
“This was a really exceptional site,” says co-author Paul Breeze at
King’s College London. The team also re-examined the nearby site of
Jubbah.
The lakes at Khall Amayshan-4 existed about 400,000, 300,000,
200,000, 130,000-75,000 and 55,000 years ago. In each case, the team
found stone artefacts left by hominins. But no two assemblages were the
same. The oldest two contained mostly hand-axes, but of different
designs. The three more recent ones featured stone flake tools, which
are evidence of fairly complicated tool manufacture, but again the
designs were significantly different. The team argues that each group of
artifacts represents a separate migration into the area, by a different
group – and perhaps different species.
The most recent occupation, about 55,000 years ago, is around the time when our species (Homo sapiens ) expanded out of Africa into Europe and Asia ,
and even to Australia. This happened between 80,000 and 40,000 years
ago, says co-author Eleanor Scerri at the Max Planck Institute for the
Science of Human History in Jena, Germany. The people at Khall
Amayshan-4 55,000 years ago may have been part of that diaspora , she says.
It isn’t certain who any of the occupants were, though, because no
hominin bones were found. The occupation 400,000 years ago was before H. sapiens evolved .
Some assemblages may represent African hominins moving into the Arabian
peninsula, but some of the artefacts look Neanderthal – suggesting Neanderthals came in from Eurasia, says Groucutt.
The temporary lakes formed when the Arabian climate temporarily
became wetter, so rivers flowed between the sand dunes and lush
vegetation grew. In a second study published last week, a team led by Andrea Manica at the University of Cambridge simulated the climate of the Arabian peninsula and north-east Africa over the past 300,000 years, to figure out when conditions were best for hominins to migrate from Africa to Asia .
Manica says his team took “two approaches”, which “ended up giving us
pretty much the same answer”. The first asked how much rainfall humans
need to survive. “If you look at the distribution of where
hunter-gatherers are right now, they completely disappear below 100-90
millimetres of rainfall per year,” he says. Similarly, areas with less
than 100 millimetres of rainfall tend to have very few grazing animals,
which hunter-gatherers rely on for food.
The team created maps of rainfall at different times in the past
300,000 years and looked for periods when continuous corridors of rainy
climates existed, which humans could have expanded into and thus reached
Asia. The simulations identified several windows when the climate was
suitable for human populations to expand from Africa into Asia.
The windows largely matched the occupations found at Khall
Amayshan-4. “Their episodes line up remarkably well with ours,” says
Manica. For instance, the Nile and Sinai regions were liveable between
246,000 and 200,000 years ago – in line with an Arabian peninsula
occupation about 200,000 years ago. This area reopened between 130,000
and 96,000 years ago, potentially explaining the occupation
130,000-75,000 years ago.
The Arabian peninsula was only intermittently inhabited, says Scerri,
in contrast to other regions with more equable climates. That may mean
it was a boundary where different hominin groups could sometimes meet.
For Groucutt, this suggests that humans and Neanderthals may have
interbred in Arabia. Today, everyone whose ancestry is mostly
non-African carries some Neanderthal DNA. This suggests that the two
groups met shortly after the out-of-Africa expansion began. Exactly
where is uncertain. Thanks to Khall Amayshan-4, says Groucutt, Arabia is
now a place where we have Neanderthal-style tools and human-style tools
very close in time, which suggests that the two species were there at
similar times, and so might have been able to interbreed.
The two studies also have implications for the route hominins took when moving from Africa to Asia .
The two main possibilities are a northern route through the Nile and
Sinai, and a southern route across the Bab-el-Mandeb strait: the
narrowest point of the Red Sea between Africa and the Arabian peninsula.
Manica’s team looked at both. “We find that quite often they are both
available,” he says.
For Groucutt, finding multiple occupations in north-west Arabia “quite strongly supports the northern route”.
Manica argues that both routes may have been used at different times.
“There is no reason why the same route would have been taken every
time,” he says. In his simulations, the northern route was “quite
challenging” about 60,000 years ago, whereas the southern route was
ideal. One possibility is that people used the northern route for the
earlier migrations, but by 60,000 years ago they had developed boats or
rafts, and could use the southern route. Manica points out that modern humans reached Australia at least 50,000 years ago , which requires sea crossings far more challenging than the Bab-el-Mandeb strait.
For Manica, the baffling thing is why it took so long for humans to
successfully expand out of Africa, when the climate repeatedly enabled
it. The earlier wet spells were actually better than the one about
60,000 years ago. “They came out at a period that was OK but not the
ideal period,” he says.
Whatever enabled the successful final migration, it wasn’t the
climate, says Manica. It may be that Eurasian hominins like Neanderthals
and Denisovans were in decline and therefore there was less competition – but that just raises the question of why they were in decline.
Zdroj: New Scientist
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7200-year-old DNA suggests Denisovans bred with humans on Sulawesi
For the first time, DNA has been obtained from the bones of a Stone Age person who lived on the Indonesian island of Sulawesi. The genetic information sheds light on the prehistory of the South-East Asian islands – including what happened when our species, Homo sapiens , first reached the area.
Sulawesi is one of the largest islands in South-East Asia, the region between the Asian mainland and Australia. On the island’s South Peninsula, researchers have excavated a cave called Leang Panninge. There, they found the buried remains of a young woman. She was about 17 years old when she died, about 7200 years ago.
The woman belonged to a Stone Age hunter-gatherer culture known to archaeologists as the Toaleans. “They made this very distinctive culture with very sophisticated types of stone tools, these beautiful little arrowheads with toothlike serrations along the edges,” says Adam Brumm at Griffith University in Australia.
The only evidence of these people is from Sulawesi’s South Peninsula, from between about 8000 years ago and 1500 years ago. “This is the first skeletal remains of a Toalean woman,” says Brumm. He and his colleagues sent one bone for DNA extraction. They didn’t expect to get anything, because Sulawesi has a hot and wet climate, which degrades DNA rapidly. But to their surprise the bone did yield DNA – albeit badly degraded. “I guess we just got lucky,” says Brumm.
The woman’s DNA was most similar to that of modern Aboriginal Australians and Papuans. The simplest explanation is that she is descended from the first wave of modern humans who entered South-East Asian islands from the Asian mainland more than 50,000 years ago . Some of those people travelled all the way to Australia or Papua New Guinea , but others settled in places like Sulawesi – ultimately giving rise to groups like the Toaleans.
The Toalean woman’s DNA isn’t a perfect match for any known modern population, so the Toaleans “seem to have left no descendants as far as we can tell”, says Brumm. But he adds that there is still limited human genetic data from Sulawesi, so it is possible the Toaleans’ descendants have simply not been identified.
About 2.2 per cent of the woman’s DNA came from the Denisovans : a mysterious human group known from a handful of sites in Asia who interbred with modern humans. “It’s now possible that Sulawesi could be where our species encountered and interbred with the Denisovans,” says Brumm.
This has been suggested before , because Denisovan DNA is particularly common in people from Papua New Guinea and the Philippines.
Zdroj: New Scientist
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7200-year-old DNA suggests Denisovans bred with humans on Sulawesi
For the first time, DNA has been obtained from the bones of a Stone
Age person who lived on the Indonesian island of Sulawesi. The genetic
information sheds light on the prehistory of the South-East Asian
islands – including what happened when our species, Homo sapiens , first reached the area.
Sulawesi is one of the largest islands in South-East Asia, the region
between the Asian mainland and Australia. On the island’s South
Peninsula, researchers have excavated a cave called Leang Panninge.
There, they found the buried remains of a young woman. She was about 17
years old when she died, about 7200 years ago.
The woman belonged to a Stone Age hunter-gatherer culture known to
archaeologists as the Toaleans. “They made this very distinctive culture
with very sophisticated types of stone tools, these beautiful little
arrowheads with toothlike serrations along the edges,” says Adam Brumm at Griffith University in Australia.
The only evidence of these people is from Sulawesi’s South Peninsula,
from between about 8000 years ago and 1500 years ago. “This is the
first skeletal remains of a Toalean woman,” says Brumm. He and his
colleagues sent one bone for DNA extraction. They didn’t expect to get
anything, because Sulawesi has a hot and wet climate, which degrades DNA
rapidly. But to their surprise the bone did yield DNA – albeit badly
degraded. “I guess we just got lucky,” says Brumm.
The woman’s DNA was most similar to that of modern Aboriginal
Australians and Papuans. The simplest explanation is that she is
descended from the first wave of modern humans who entered South-East Asian islands from the Asian mainland more than 50,000 years ago . Some of those people travelled all the way to Australia or Papua New Guinea , but others settled in places like Sulawesi – ultimately giving rise to groups like the Toaleans.
The Toalean woman’s DNA isn’t a perfect match for any known modern
population, so the Toaleans “seem to have left no descendants as far as
we can tell”, says Brumm. But he adds that there is still limited human
genetic data from Sulawesi, so it is possible the Toaleans’ descendants
have simply not been identified.
About 2.2 per cent of the woman’s DNA came from the Denisovans : a mysterious human group
known from a handful of sites in Asia who interbred with modern humans.
“It’s now possible that Sulawesi could be where our species encountered
and interbred with the Denisovans,” says Brumm.
This has been suggested before , because Denisovan DNA is particularly common in people from Papua New Guinea and the Philippines.
Zdroj: New Scientist
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Artificially stripped-back cell is still able to rapidly evolve
An artificial “minimal cell” that has had all but the most essential
genes stripped out can evolve just as fast as a normal cell. The finding
shows that organisms can rapidly adapt, even with an unnatural genome
that provides little flexibility.
“It appears there’s something about life that’s really robust,” says Jay T. Lennon
at Indiana University in Bloomington. “We can strip it down to just the
bare essentials,” he says, but that doesn’t stop evolution going to
work.
Lennon and his team studied a bacterium called Mycoplasma mycoides , a parasite that lives in the guts of animals like cows. Because it gets most of its nutrients from its host, M. mycoides has naturally lost a lot of genes.
In 2016, researchers led by Craig Venter at the J. Craig Venter Institute in California reported that they had stripped the bacterium’s 901-gene genome back even further, to just 493 genes. The resulting synthetic organism, M. mycoides JCVI-syn3B , has a “minimal genome ”, the smallest of any known free-living organism.
M. mycoides JCVI-syn3B can grow and divide normally, but
Lennon wondered what would happen to it in the long term. Species need
to change to survive, but it seemed likely that the minimal cell would
have trouble evolving.
“Every single gene in its genome is essential,” says Lennon. “The
cell has zero degrees of freedom.” As a result, any mutations that
arise would be expected to be harmful.
Lennon’s team began by establishing that the minimal cell could still
mutate. It does so to such a degree that, even given a small population
size of just 10 million, every single genetic “letter” would be
expected to mutate more than 250 times over 2000 generations.
The team then grew M. mycoides JCVI-syn3B in the lab, allowing them to evolve freely for 300 days.
Next, the team set up some head-to-head contests. In some
experiments, the minimal cells that had evolved for 300 days were pitted
against the original, non-minimal M. mycoides . In others, the non-minimal cells went up against minimal cells that hadn’t evolved for 300 days.
In all contests, the team put equal quantities of the strains being
assessed in a container and observed which one became more common, a
sign of which was better suited to its environment.
The unevolved minimal bacterium was “really sick”, says Lennon, and
was easily outcompeted by the non-minimal version. But the version that
had evolved for 300 days did much better, recovering 80 per cent of the
lost fitness (bioRxiv, doi.org/grck ).
Crucially, the team identified the genes that changed most during these evolution contests, says Zan Luthey-Schulten
at the University of Illinois at Urbana-Champaign, who wasn’t involved
in the study. Some have unknown functions. “You have to go and
ask yourself, ‘What does that thing do?’ ” she says.
Zdroj: New Scientist
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Harvestman genome helps explain how arachnids got grasping legs
Some spider-like animals grow long legs that wrap and grasp like a monkey’s tail – and a genetic study has helped establish how they develop. Harvestmen, or daddy-long-legs, are arachnids, but they aren’t spiders: they instead belong to a closely related group called the Opiliones. They have eight extraordinarily long legs that can measure up to 28 times their body length, and they can bend the tips of them to wrap around and grasp objects. However, harvestmen – like spiders, ticks and scorpions – actually have 12 limb-like appendages in total. The four at the head end develop into short jaws or pincers, or short limbs called pedipalps, which are unique to arachnids and can often detect tastes. Fascinated by the way these appendages develop differently, Guilherme Gainett at the University of Wisconsin-Madison and his colleagues teamed up with genome specialists at the Smithsonian Institution in Washington DC to draft a sequence of the genome of a lab-raised harvestman (Phalangium opilio). After identifying three genes they thought might affect how the animal’s legs develop, they engineered dozens of harvestmen embryos with different combinations of modified ways of expressing those genes. Some of the harvestmen developed deformed legs that more closely resembled the first four appendages, says Gainett. And when the team interfered with specific genetic pathways, the legs lacked the kind of segmentation – similar to joints in vertebrates – that normally allows harvestmen to curl their legs around objects. “We’ve shown… how the combinations of these genes create a blueprint in the embryo to differentiate between what’s going to be a leg that is used for walking and what is going to be a pedipalp, which can be used to manipulate food and assess the surroundings,” says Gainett. Unlike most other arachnids, harvestmen have changed little during their evolution and their genome architecture may relatively closely resemble that of the oldest arachnids that lived more than 400 million years ago. That makes them ideal models for studying arachnid genetics, says research team member Vanessa González at the Smithsonian Institution.
Zdroj: New Scientist
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Sponge fossils suggest animals already existed 890 million years ago
The origin of animals may have happened 350 million years earlier than thought. Fossils that seem to be sponges, one of the first animals to evolve, have been found in rocks from 890 million years ago.
“It seems at first glance that this is a very radical paper,” says Elizabeth Turner at Laurentian University in Sudbury, Canada, who made the discovery. However, she says the fossils she found fit with other evidence.
Animals are mostly multicellular organisms whose bodies are made up of distinct tissues, and unlike plants they have to eat food to survive. For years, the earliest-known animal fossils were from the Cambrian Period , which began 541 million years ago. However, in recent years , some fossils from the earlier Ediacaran Period (635 to 541 million years ago) have been identified as animals . There are also 660-million-year-old chemical traces that may be from sponges .
Ancient sponges Turner studied rocks from north-west Canada that contained the preserved remains of reefs from 890 million years ago, during the Tonian period. These reefs weren’t made by corals, like modern reefs, as these didn’t exist yet. Instead, they were made by photosynthetic bacteria living in shallow seas. The reefs, known as stromatolites , were many kilometres across and rose to heights of hundreds of metres above the seafloor. “These are spectacular reefs,” says Turner.
Within the rocks, Turner found the preserved remains of a network of fibres, which branched and joined up in a complex mesh. These are the remains of sponges, she argues, but “not a normal fossil”.
The bodies of modern sponges contain a mesh made of a protein called spongin, which forms a soft skeleton. Turner’s work suggests that when ancient sponges died, their soft tissues became mineralised, but the tough spongin didn’t. Eventually, though, it decayed, leaving hollow tubes within the rock that later filled with calcite crystals. These networks of calcite (pictured above) are what Turner then found – and the way the network branched looked just like spongin (pictured below).
Similar fossils from later periods have been convincingly identified as sponges, says Joachim Reitner at the University of Göttingen in Germany, who has studied preserved sponges . “We have no other organisms forming this type of network in this way.”
“I personally found this pretty convincing,” says Amelia Penny at the University of St Andrews in the UK.
Early origins If sponges existed 890 million years ago, then the origin of animals must have occurred much earlier than previous fossils have suggested. “Molecular clock” studies that use modern DNA to estimate when key points of evolution occurred have indicated that animals emerged long before the earliest fossils. However, this approach is often thought to be less reliable when there aren’t any fossils available to calibrate the molecular clock. Turner’s finding “brings the fossil record back into line with the molecular clock estimates”, says Penny.
However, an earlier origin of animals changes two key aspects of their story on Earth. Firstly, there was little oxygen in the air until levels rose between 800 and 540 million years ago . This rise in oxygen is thought to have enabled the evolution of animals, but if animals already existed 890 million years ago, it suggests that the first and simplest animals could survive with little oxygen , says Turner. In line with this, Reitner says many modern sponges can tolerate low-oxygen conditions .
Secondly, most of the planet froze over in the period between 720 and 635 million years ago, becoming a “snowball Earth ”. “It’s previously been thought these are really catastrophic events for life on Earth, certainly multicellular life,” says Penny. But it seems sponges, at least, survived the glaciations.
“They did not wipe out all the products of biological evolution to date, and life did not have to start all over again, because the things I’ve identified are essentially identical to sponge fossils [from much later],” says Turner.
Sponges vs comb jellies Finally, there is the question of which animal groups were the first to emerge. Palaeontologists have generally assumed that sponges were first, but in the past decade some genetic studies have suggested that comb jellies – which superficially look like jellyfish – actually preceded them. The debate is ongoing: Penny would only say that finding early sponges doesn’t mean there weren’t also comb jellies very early, because such soft-bodied animals are rarely preserved.
Zdroj: New Scientist
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Robotic chemist may be able to recreate Earth’s primordial soup
Recreating the mix of compounds and experimental conditions that
interacted over billions of years to create life on Earth is impossible
in the lab. But an autonomous robot can shorten the time it takes to
test each possible mixture, which could help reveal the precise
combination that let proteins, DNA and enzymes emerge from the prebiotic
soup on early Earth.
Lee Cronin at the
University of Glasgow, UK, and his colleagues built a robotic chemist
that can mix simple molecules together, watch them react, analyse the
result and then decide what to add to the reaction. Over several weeks,
this robot can start to recreate a prebiotic soup scenario with almost
no input from human chemists, he says.
“We wanted to remove the bias from the experiments and cover as much
chemical space as possible to look for the spark of life,” says Cronin.
The set-up includes a tangle of tubes connecting 18 flasks of
different starting materials to a central reaction vessel containing a
range of clean, dry minerals such as quartz, ulexite and pyrite.
The starting materials are all small molecules with no biological or
catalytic function, including simple acids, organics, reducing agents
and some inorganic molecules like copper sulphate.
The robot chooses two or three of these reagents to suck into the
reaction vessel, where the mixture is stirred and heated for an hour,
then allowed to settle. It analyses the sample, and a portion is taken
away for storage and human analysis later. A small amount of the brew is
left as a seed mixture, and the robot then adds a fresh batch of
reagents, and the process repeats. The team ran the robot for up to 150
of these cycles over many days.
The robot’s decisions on whether to let a reaction continue or to
introduce a molecule into the brew are based on readings from a mass
spectrometer, which reveals the size of the different molecules within the mixture.
If these readings suggest no change has happened in the mixture, the
robot will work to push the system back away from a state of equilibrium
by adding something new in the next cycle. “It’s an anti-boredom
algorithm,” says Cronin.
The robotic chemist doesn’t allow us to work out how life formed
yet, but it is a useful tool to let us step towards it – and a vast
improvement on the effort one person at the bench could make, says Sijbren Otto at the University of Groningen in the Netherlands.
“The problem with chemical space is it’s more than astronomical
[space], so you cannot possibly cover it at all,” says Otto. But with
the right mix of starting materials that might not be a problem. “The
hope with these experiments is that something autocatalytic emerges from
it,” he says, meaning when a reaction produces its own catalyst in the
process. Autocatalytic reactions are considered essential for life to
emerge.
Judit Šponer at the Czech Academy of Sciences says that in origin-of-life experiments , humans tend to get in the way. But Cronin’s work significantly reduces human bias, she says.
Cronin is encouraged by what has happened so far. “We’ve seen
tentative evidence of molecular replication,” he says. Complex molecules
are forming, and despite being diluted away at the start of each new
cycle, those molecules persist, he says.
Cronin is planning a bigger version of the robot. “This is a dummy
run,” he says. With more complex algorithms, the team will hope to see
evidence of large, complex molecules that can process information.
Zdroj: New Scientist
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Researchers Say They've Finally Sequenced the Entire Human Genome
An international team of scientists claims to have
reconstructed the entire human genome, closing the gap of missing
sections left out when the first human genome was sequenced 20 years
ago, according to a preprint study shared late in May .
In
2000, leaders from the Human Genome Project and Celera Genomics
announced they had sequenced the first human genome from the White House
lawn. But if this latest claim is confirmed as true, the remaining 8%
of the human genome has officially been mapped, and we finally know, to
the most basic genetic precision, what we're made of.
New DNA sequencing results are 'a technical tour de force' Assuming
this is for real, the gap in our grasp of human genes was filled with
new technology, but the new tech has its own limitations. For example,
the kind of cell line employed to hasten the mapping process. "You're
just trying to dig into this final unknown of the human genome," said
Karen Miga, a researcher at the University of California, Santa Cruz,
who was one of the leaders of the international group working to
sequence the entire human genome, in a Stat News report .
"It's just never been done before and the reason it hasn't been done
before is because it's hard." Miga stressed that she isn't going
official with the paper until it receives peer-review and is published
in a legitimate medical journal.
However, assuming the findings are correct, this is a substantial advancement in genetics ,
which was made possible via new DNA sequencing tech developed by two
private firms: Oxford Nanopore, in Oxford Science Park, U.K., and
Pacific Biosciences of Menlo Park, California. The two companies'
technology possesses minute but crucial advantages over conventional
tools of the last several decades. Deputy Director-General of the
European Molecular Biology Laboratory said the results were "a technical
tour de force," according to the Stat News report. The initial
genome studies were cautious, since no single sequencing process worked
through the entire DNA molecule, added Birney.
Closing even minor gaps in DNA can open the door to the regulation process of genes "What
this group has done is show that they can do it end-to-end," explained
Birney. This opens the door to more research, because, (if confirmed)
scientists have proof that the entire DNA molecule
can successfully be sequenced. But while this could serve to
incentivize genetic research, the question remains: Is this "missing
link" of the genetic code really that important? The international group
said it had increased the number of DNA bases to 3.05 billion, from
2.92 billion, a jump of 4.5%. By contrast, the new number of genes that
code proteins grew to 19,969, a rise of only 0.4%. While this might be a
let-down, it could also bring other scientists closer to further
discoveries, including uncovering the regulation process of genes.
Notably,
the DNA sequence used for the study wasn't taken from a person, but
from a growth in a woman's uterus called a hydatidiform mole, which
happens when sperm fertilize an egg that lacked a nucleus. This leaves
the cell with two copies of the same 23 chromosomes, instead of two
distinct sets (which is what typical human cells have). There's much to
explore in this new technology, and the substantial progress we've seen
in DNA sequencing technology in the last 20 years. And if this study
checks out, we are living in one of the most exciting moments in the history of science (although, it's pretty clear that we already were).
Zdroj: web
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The human genome has finally been completely sequenced after 20 years
We have finally sequenced the complete human genome. No, for real this time.
When scientists first announced that they had read all of a person’s DNA 20 years ago, they were still missing some bits. Now, with the benefit of far better methods for reading DNA, it has finally been possible to read the whole thing from end to end.
“Having been part of the original Human Genome Project in 2001, and especially focused on the difficult regions, it’s really satisfying for me to see this done even though it took 20 years,” says Evan Eichler at the University of Washington in Seattle.
The new genome includes an additional 200 million base pairs or “letters” of DNA, and adds more than 2000 extra genes.
Our genes help make us who we are. Humans have thousands of them, although the exact number is uncertain and partly depends on how you count them. They are stored on long molecules of DNA in the centres of cells. The genetic information exists as four molecules called bases (C, G, T and A) that are strung along the DNA molecule.
The human genome contains just over 3 billion letters . The first complete sequences were published to huge fanfare in 2001: one by the International Human Genome Sequencing Consortium (HGSC) and the other by US company Celera Genomics . The project had begun a decade before in 1990.
Because the genome had to be read in small chunks and then reassembled, some highly repetitive sections proved impossible to place, a bit like a jigsaw where all the pieces look alike.
Missing parts Over the next three years, the HGSC filled in some of the gaps, and in 2004, the consortium announced that it had done all it could. Geneticists have continued to improve the reference genome, but largely by improving the accuracy of existing sequences, rather than by adding new ones. About 8 per cent was still either missing or likely to be wrong.
The new version of the genome has been created by the Telomere-to-Telomere consortium, led by Karen Miga at the University of California, Santa Cruz, and Adam Phillippy at the National Human Genome Research Institute in Maryland. In 2018, they were part of a team that sequenced big chunks of the genome, more than 100,000 bases long, enabling them to fill in some missing parts. “She [Miga] called me up and said ‘I want to finish the genome’,” says Phillippy. “I said, ‘I do too’.”
They chose to read the DNA from a cell line called CHM13. It comes from a mass of tissue called a hydatidiform mole, a kind of failed pregnancy in which an egg in a uterus somehow lost its genome, and was then fertilised by a sperm. The resulting cell only had half the DNA of a normal embryo, so the sperm’s DNA was duplicated. Such cells form dangerous growths, like cancers, and have to be removed. They can then be grown in the lab – seemingly indefinitely.
“It’s unique in this way, in that it’s not the genome of anyone who ever lived,” says Phillippy. The DNA came from a single sperm, so it is half the genome of a potential father, which has been duplicated.
The cells were collected consensually several decades ago, but the identity of the donor was anonymised by a company that has since gone out of business, so it isn’t known from whom they came.
“We can’t really figure out [even] if we wanted to who it was from originally,” says Phillippy.
Normal human cells have two copies of every stretch of DNA, which often have significant differences because one comes from the mother and one from the father. This makes it harder to sequence the DNA accurately, because it’s tricky to tell what is a mistake in sequencing and what is a genuine difference. Using CHM13 avoids this problem, because the two copies are virtually identical.
Complementary sequencing techniques To assemble the genome’s sequences, the team combined two technologies. One was a type of sequencing that reads extremely long stretches, over a million letters long, and the other was a type that delivers extremely high accuracy and can thus handle sections that are very slightly different – such as multiple copies of the same gene.
Human DNA is stored on large molecules called chromosomes that have four arms joined in the centre to form an X shape. Much of the hard-to-read DNA was from around the central points, known as centromeres. Furthermore, some chromosomes are lopsided, with one pair of arms shorter than the other: the short arms contain a lot of difficult DNA.
As a first pass, in August 2020, the team published the complete human sex-determining X chromosome. They have now released the entire human genome.
The new version adds nearly 200 million letters to the previous version, with 2226 sections that are near-identical copies of known genes. Of these new genes, the team predicts that 115 code for proteins.
What is a gene? Phillippy emphasises that these numbers are uncertain. “The definition of what is a gene is still a bit messy,” he says. Genes were traditionally thought of as sections of DNA that code for a protein, but in fact, many genes are non-coding and have other functions. The new genome has 63,494 genes, compared with 60,090 in the last update made in 2019 . Genes that code proteins number 19,969, up from 19,890.
“It’s much, much better than anything we had,” says Aida Andrés at University College London.
In a second paper, Eichler’s team has focused on segmental duplications: long stretches of DNA that have been copied again and again. Unlike “junk DNA ”, which is often seemingly meaningless repetitions, segmental duplications include genes and other sequences that have recognisable functions. Because of them, people can have many copies of some genes.
Segmental duplications accounted for nearly one-third of the new sequence, and make up 7 per cent of the genome. Their sequences also varied more than non-duplicated regions did.
Eichler thinks segmental duplications have played a key role in human evolution. “They are the place in the genome where new genes are likely to be born,” he says, because one of the copies is free to vary. Humans have several duplicated genes, which he says were seemingly “critical in building a bigger brain that distinguishes us from other apes ”.
Even if the duplicated genes don’t become significantly different, they can still have profound effects if they simply mean a protein gets made in larger quantities, says Andrés. She says segmental duplications cannot explain all of human evolution, because it was surely a hugely complex process, “but they are important”.
Turning DNA on and off The new genome will make it much easier to study duplicated genes, says Andrés, because the sequences it lists for them are much more likely to be correct than earlier versions.
It is crucial to understand segmental duplications because some of them underpin genetic disorders , says Eichler.
In a third paper, a team led by Winston Timp at Johns Hopkins University in Baltimore has examined marker chemicals called methyl groups that attach to DNA at various points. These “epigenetic” markers affect which genes are turned on and off. Timp’s team used the new genome to map methylation in the newly explored areas.
They found that levels of methylation are low around the centromeres at the heart of the chromosomes. These regions are crucial for reproduction and cell division.
When this goes wrong, the results can be dangerous. “In cancer, you will often gain an entire chromosome or lose an entire chromosome,” says Timp. In the long run, understanding how cell division works, and the role methylation might play, could point the way towards new cancer treatments.
Zdroj: New Scientist
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The first complex cell may have had dozens of nuclei instead of one
We may have imagined our most distant ancestor wrongly. The first complex cell may have been bigger and even more internally complex than anyone suspected – and that may have helped it survive. Over a billion years ago, evolution gave rise to the first complex cell. It is often pictured as something like an amoeba or a white blood cell: a roughly spherical blob with a single packet of DNA at its core. But a new study argues that is wrong. Instead, it says the first complex cell was much larger and didn’t have just one packet of DNA: it had several, perhaps dozens. Having multiple copies of its genes would have helped it survive and adapt, the researchers say. “It’s a really interesting new idea,” says Emmanuelle Javaux at the University of Liège in Belgium, who wasn’t involved in the study. Most researchers never even thought to question the number of DNA stores, she says. Cells are integral to life. They are bubble-like receptacles that contain DNA, protein and the other vital molecules. Most living cells have relatively simple internal structures and fall into one of two groups: bacteria and archaea. But some – a group called eukaryotes – have bigger and more intricate cells. A eukaryotic cell has a central nucleus where it keeps its DNA, and sausage-shaped bodies called mitochondria that supply it with energy. All animals, plants and fungi are eukaryotes, making the event that was the origin of eukaryotes crucial for understanding the evolution of complex life. It is a deeply mysterious event, but we do know it involved some sort of coming together of an archaean cell and a bacterium, in which the bacterium became the first mitochondrion. The result was a massive energy boost for the host cell, but also a lot of new problems. The first eukaryotes essentially had two sets of genes – one archaeal, one bacterial – and they would have disrupted each other. The risk of lethal mutations must have been high. Over the past 5 years, Sriram Garg and William Martin at the University of Düsseldorf in Germany have suggested one way the first eukaryotes might have coped. The solution, they say, was for the cell to grow larger, and host multiple nuclei. “You’re talking about a host cell that is not dividing, but the nucleus continues to divide,” says Garg. Having multiple nuclei would have given the first eukaryotes a buffer. If one copy of a gene became damaged, another nucleus would still have a working version. As a result, the cell itself could experience the advantages of genetic mutation without the disadvantages. Not only would it be less likely a lethal genetic mutation would kill the eukaryote, but with all those nuclei, there would have been more chance of a given gene in one nucleus mutating into a form that significantly improved the ability of the eukaryote to survive in its environment. “It permits more flexibility, more genetic diversity,” agrees Javaux. Now Garg has evidence. Multinucleate cells are widespread among eukaryotes: they are very common in fungi, and our bodies contain bone cells called osteoclasts that are multinucleate. Garg and his colleagues compiled data on 106 eukaryotic groups, noting which of them were known to make multinucleate cells. Based on how the different groups are related, the researchers worked back to the shared ancestor of all of them. They concluded that the ability to form multinucleate cells probably dates back to the last shared ancestor of all modern eukaryotes.That’s intriguing, says Javaux, but “I’m not sure it’s enough to prove it”. A key question – one Garg acknowledges – is that we don’t know how most eukaryotic multinucleate cells arise. It can happen when a cell doesn’t divide – which is what Garg is proposing for the first eukaryotes – but it can also happen when two or more cells fuse. “If you don’t know the origin of that state in each supergroup, it’s difficult to say if this is an ancestral state or a convergence of evolution,” says Javaux.
Zdroj: New Scientist
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Ancient hominins may have needed midwives to help deliver babies
It isn’t just modern humans that have found giving birth painful and
dangerous. Growing evidence suggests birth was difficult for our hominin
relatives millions of years ago. As a result, earlier hominins like Australopithecus may have needed help to deliver their babies.
Birth is strikingly dangerous for modern humans compared with other primates. Globally, for every 100,000 births in 2017, 211 mothers died .
In the worst-affected countries, such as South Sudan, the maternal
mortality rate is more than five times that. Many nations have much
lower rates, but that is largely due to better medical intervention,
including caesarean sections – which weren’t available for most of our
species’ existence.
The same isn’t true for primates including monkeys, our closest
living relatives. “You’re not seeing these types of complications that
you see in humans,” says Nicole Webb at the University of Zurich in
Switzerland.
The long-standing explanation for the difficulty of human births is
that it is caused by a combination of our large brains and the fact we
walk upright on two legs. According to anthropologist Sherwood Washburn, writing in 1960, upright walking meant evolution favoured a narrower pelvis , but also a wider pelvic canal to accommodate the baby’s head – creating what he dubbed the “obstetrical dilemma”.
Despite challenges and modifications to the idea, for many
anthropologists, it still largely holds true. “In my view, the
obstetrical dilemma hypothesis as Washburn framed it is still the most
reasonable,” says Martin Haeusler at the University of Zurich.
It was generally thought that the obstetrical dilemma was unique to humans, or at least to the Homo genus, but new evidence suggests birth difficulties go back much further.
Webb and her colleagues have examined the birth canals of
chimpanzees, which were thought to be much more spacious than those of
humans. In a talk at the annual meeting of the American Association of Physical Anthropologists, held online last month , she explained that this assumption partly stems from a famous 1949
study by Adolph Schultz, which demonstrated that the entrance to the
chimpanzee birth canal was almost twice as wide as the fetus’ head .
However, Webb argued that Schultz measured the wrong parts of the
pelvis: chimpanzee births work differently to human births, so the
tightest fits are in different places. She then described how she has
made her own measurements of 29 chimpanzee pelvises and found that in
the tightest spot, the fetus’ head is 85 per cent of the size of the
canal: still looser than what is found in humans, but not by much.
“We looked at the more relevant dimensions of the birth canal,” says Webb. “It’s not like chimpanzees have all this space.”
She suggested there was a shift in the evolution of great apes, whose
pelvises are different from those of monkeys. Many monkeys can stretch
the cartilage that joins the left and right halves of the pelvis at the
front, creating a wider opening, but chimpanzees can’t do that.
“Our closest ancestors already had some of the same features [as
humans], including not having so much flexibility in the front part of
the pelvis to accommodate birth,” says Webb.
In another talk at the conference ,
Natalie Laudicina at Grand Valley State University in Allendale,
Michigan, described how she had mapped the entire birth canals of five
hominins: four Australopithecus specimens from three species, including the famous Lucy , and one Neanderthal.
“Every species is different,” says Laudicina. But with the exception of the 2 million-year-old Australopithecus sediba ,
all the species she looked at faced a tight squeeze, and she says the
babies would have had to rotate to get through the birth canal. Human
infants have to twist and turn to get out, which is a big part of why
birth is so complicated. Laudicina says her research suggests that many
earlier hominins faced similar problems and didn’t have easy births like
most non-human primates.
She emphasises that the full story isn’t yet available, because the
five pelvises she looked at represent pretty much all the hominin
pelvises known. “It’s hard to pinpoint exactly when modern human
childbirth started, because we only have one specimen per 2 million
years,” she says.
But if Australopithecus had difficult and complicated births, mothers may have needed help during labour. “I think we’ve underestimated what Australopithecus
[went] through,” says Webb. Other adult females, perhaps those who had
already given birth, may have acted as midwives. “I think it’s something
we need to entertain as a possibility,” she says.
Most primates leave their groups to give birth, suggesting they do it
alone – although they also tend to do it at night, so observations are
few and far between. But there have been a handful of exceptions: captive female bonobos have been seen seemingly helping other females in labour , and there are isolated reports of similar behaviour in monkeys .
Zdroj: New Scientist
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From genes to public health: are we ready for DNA-based population screening?
The
opinions expressed in the paper are those of the authors and do not
necessarily reflect those of the Centers for Disease Control and
Prevention.
Recognizing
the emerging role of genomics as a tool for population screening, the
American College of Medical Genetics and Genomics (ACMG) has generated
two companion guidance documents on DNA-based screening of healthy
individuals that appear in the present issue of Genetics in Medicine .1 ,2
In this commentary, we offer a brief public health perspective on these
documents in the context of recent work from the Centers for Disease
Control and Prevention (CDC) Office of Genomics and Precision Public
Health (OGPPH).
Since
the start of the Human Genome Project, there has been a strong belief
by scientists and the public that at some point in the future, all of us
will have our genomes sequenced in routine health care. In 1999, Dr.
Francis Collins articulated a vision for the practice of medicine in
2010 in a hypothetical case of a 23-year-old man who presents to his
health-care provider as part of a health checkup and is offered genetic
testing for various diseases, to develop a personalized plan for disease
prevention and screening.3
However, the complexities of the science and the cost of technology,
the need for large scale clinical and population studies, and a host of
ethical, legal, and social issues (ELSI) have prevented this prediction
from becoming a reality. Nevertheless, steady progress in science and
technology, the conduct of clinical and population studies around
clinical validity and utility of genetic information, as well as
numerous investigations around ELSI, have helped us move closer to this
vision. So much so that the new National Human Genome Research Institute
(NHGRI) 2020 strategic vision for improving health at the forefront of
genomics includes a bold prediction for 2030: “The regular use of
genomic information will have transitioned from boutique to mainstream
in all clinical settings, making genomic testing as routine as complete
blood counts.”4
In
the United States, the vision presented above has begun to be realized
in multiple health systems and population studies carrying out large
scale population sequencing in biobanks and learning health systems
research settings, such as Geisinger Health System and the Nevada Genome
Project.5
Nevertheless, in 2020, almost all the implemented applications in
genomics in routine clinical care occur in diagnostic settings, most
notably in the diagnosis of rare genetic diseases, noninvasive prenatal
testing, and cancer genomics to guide cancer therapy. In addition, there
are limited data on the implementation of testing and its impact on
public health.6
GENOMICS AND POPULATION SCREENING: “WE SCREEN NEWBORNS, DON’T WE?” The
use of genomics as a population screening tool long predates the Human
Genome Project. Newborn screening is considered as one of the ten great
public health achievements of the twentieth century.7
For more than 60 years, newborn screening has been a component of
public health programs and has led to major improvements in outcomes for
infants with various genetic, metabolic, and other conditions. In the
United States, newborn screening identifies >13,000 newborns annually
who will require lifelong specialized health care.8
Recognizing
the emerging role of genomics as a screening tool across the lifespan,
in 2013 Evans et al. called for scientific investigation of the
application of genomics in adults in a similar way to newborn screening.9
The authors urged that a partnership be developed between the genomics
and public health communities to better identify individuals who have
genetic variants with a high risk of preventable diseases.
CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC) TIER 1 GENOMIC APPLICATIONS In 2014, CDC developed a relatively simple horizon-scanning method based on a three-tier classification system:
“Tier 1 […] genomic applications have a base of synthesized evidence that supports implementation in practice.
Tier 2 […] genomic applications have synthesized
evidence that is insufficient to support their implementation in routine
practice. Nevertheless, the evidence may be useful for informing
selective use strategies […]
Tier 3 […] applications either (i) have synthesized
evidence that supports recommendations against […] use, or (ii) no
relevant synthesized evidence is available.”10
For the past few years, CDC has worked with
health-care organizations and public health programs to implement
evidence-based recommendations for three primary tier 1 applications
involving screening for hereditary breast and ovarian cancer (HBOC),
Lynch syndrome (LS), and familial hypercholesterolemia (FH). This work
has included public and provider education, special programs that
address disparities in access to testing and services, conducting public
health surveillance, and policy development.11
It is important to note that the CDC tier 1 designation is associated
with the clinical scenario for testing, not the underlying condition.
For example, we are not aware of any current recommendations, or
synthesized evidence, to support population screening for BRCA1 and BRCA2 pathogenic variants, but there are evidence-based recommendations for screening based on family history and ethnicity.11 The former application of screening for BRCA1 and BRCA2 pathogenic variants could thus be considered tier 3, and the latter application tier 1.
AN EVOLVING RATIONALE FOR DNA-BASED ADULT SCREENING Increasingly,
accepted evidence-based approaches using family history–based screening
do not identify most individuals with genetic conditions associated
with the three primary CDC tier 1 applications. Several studies have
shown that a minority of adults with pathogenic BRCA1/2 variants are aware that they carry these variants.5
This may be due to limitations to the uptake of family history and the
sensitivity of the family history–based approach. The evidence of
failure to identify at-risk individuals is occurring in the context of
rapidly declining costs of DNA testing, and improved ability for
interpreting pathogenicity of DNA.5
It is estimated that about 1% of the population carries a pathogenic DNA variant associated with familial hypercholesterolemia (LDLR , APOB , PCSK9 ), HBOC (BRCA1 , BRCA2 ), or LS (MLH1 , MSH2 , MSH6 , PMS2 ).5
DNA-based population screening for these genes can potentially offer
short-term benefit for the estimated 3 million individuals in the United
States with one of these risks, and longer-term benefit to more people
as the number of genes proposed for population screening increases. It
is important to note that population screening is distinct from
diagnostic testing. Population screening should be evidence-based and
adhere to the screening criteria established by Wilson and Jungner
several decades ago.5
In
2018, the Genomics and Population Health Action Collaborative (GPHAC)
of the Roundtable on Genomics and Precision Health of the National
Academies of Sciences, Engineering, and Medicine evaluated the potential
for DNA-based screening programs in healthy adults. This group
developed a roadmap for implementation that should be considered when
developing a population-based sequencing program.12
The group also identified important issues to address such as
feasibility of screening, potential benefits and harms, outcomes, costs,
and ultimately, clinical utility.
ACMG POINTS TO CONSIDER GUIDANCE DOCUMENTS ON ADULT DNA-BASED SCREENING The
first ACMG points to consider (PTC) document offers guidance for
programs and sponsoring organizations that are considering DNA-based
health screening,1 and the second offers guidance to individuals and health-care providers around DNA-based screening.2
Taken together, the two documents mark an important milestone on the
road to public health genomics. They also appropriately reflect the
complexities inherent in applying genomic information to healthy
populations.
The first document has seven points to help guide
programs and sponsoring organizations. The authors review the evolving
evidence around DNA-based screening in relation to the well-known Wilson
and Jungner criteria13
for population screening. The document concludes that DNA-based
screening efforts have the potential to improve population health, but
only if risk identification is effectively combined with evidence-based
risk-reducing clinical care. The document embraces the list of genes
associated with the CDC tier 1 genomic applications as a core list for
consideration in the context of population screening. The conditions
involved in the three primary tier 1 genomic applications are
specifically associated with risk for breast, ovarian, colon, and
endometrial cancers; coronary artery disease; and stroke and are
therefore consistent with Wilson and Jungner’s guidance to focus health
screening on “important health problems.” The seven points to consider
are detailed and clearly articulated throughout. The authors are to be
commended in attempting to deal with the challenging, shifting terrain
of increasing use of DNA-based health screening, in programs and
organizations, even in the absence of adequate evidence. We fully agree
with the statement that “the health service delivery options for
DNA-based health screening are currently in flux.… Much of the health
services and economic research needed to address the DNA-based screening
issues are yet to be done.”
The second guidance document is
addressed to individuals and health-care providers. It acknowledges at
the outset that while the clinical utility of genome sequencing in
apparently healthy people has not been established, accessibility to
sequencing has increased, including use by the public without any
specific clinical indication. The document explores opportunities and
challenges presented by the changing models for delivery of genetic
testing services. These include (1) a traditional genetic health-care
model of services between genetics health-care providers and a patient’s
referring provider, (2) a nontraditional genetic health-care model
where genetic services are integrated within primary care and other
specialties, and (3) a consumer-directed genetic health-care model in
which consumers initiate the process on their own without involvement of
health-care providers. The document offers a framework for the delivery
of DNA testing according to the well-known preanalytical, analytical,
and postanalytical phases of the testing process. It considers
opportunities and challenges for each step of the process and for each
health-care model, and strategies to address them.
One of the most
useful aspects of the second ACMG guidance document are the detailed
steps identified in the pre- and postanalytical phases, which can allow
exploration of important components (e.g., preanalytical education step,
informed consent, and others). The detailed descriptions in the
document allow comparison between different delivery models. This
framework provides a helpful analytic tool to evaluate the strengths and
weaknesses of each delivery model, and a careful summary of what we
know about the delivery models in the three phases, and their strengths
and weaknesses. Nevertheless, by acknowledging that the traditional
delivery model is being replaced by the nontraditional, such as consumer
genetic testing, the document appears to acknowledge the inexorable
march toward DNA screening for healthy populations even in the absence
of data on clinical utility, economic considerations, and adequate
dealing with ethical, legal, and social issues.
DNA-BASED POPULATION SCREENING: WHAT’S NEXT? The
two ACMG documents taken together reflect a new approach by marrying
the importance of an evidence-based approach of the first document
invoking principles of population screening with the importance of
ensuring the integrity, quality, and outcomes of the testing process in
the context of changing models of implementation. But the striking
differences in the guidance document’s presentation and recommendations
for individuals and providers versus programs and organizations may be
inadvertently confusing to organizations, providers, and individuals, as
it may be misinterpreted as DNA-based population screening can proceed
without evidence, since it seems to be the only way such evidence can be
gathered.
As the first ACMG document clearly shows, there are key
knowledge gaps in fulfilling criteria for population screening. One
important gap is the incomplete understanding of the “natural history of
the condition.” Natural history is concerned with the course of disease
in the absence of treatment, and it involves both penetrance, the
proportion of individuals with a given genomic risk who will show
evidence of the associated clinical problems, and expressivity, the
range of clinical manifestations associated with a specific genomic
risk. While we have a detailed understanding of many genetic conditions
in patients identified by diagnostic testing, natural history data are
limited for persons identified via DNA-based screening. If DNA-based
screening is to improve the public’s health, it must be combined with
evidence-based care that reduces the burden of disease (e.g., screening,
pharmacologic prevention). Management guidelines will need regular
reanalysis of DNA variants informed by the most updated curated
databases, regular clinical evaluation in screened individuals, the
availability of updated clinical decision support tools and linkages
with electronic health records, as well as regular assessment of the
effectiveness, benefits, and potential harms of testing and prevention
strategies. The two documents focus on DNA-based screening and
population health related to a limited number of common and well-studied
genetic disorders. Other areas where the evidence is more limited (tier
2 or tier 3) include pharmacogenomics, polygenic risk scores (PRS), and
additional monogenic conditions.
Ongoing research is needed to
evaluate genotype–phenotype correlations in longitudinal studies and
biobanks, and clinical utility studies to evaluate the effectiveness of
risk-reducing interventions in screened persons with pathogenic variants
in associated genes. We have previously proposed a collaborative
implementation research agenda embedded in learning health systems14
to create an adequate evidence base to support DNA-based screening to
improve population health. The translational research framework outlines
collaboration among multiple health systems with available genome
sequencing data and clinical outcomes. The framework is based on
evaluating the impact of genetic information on improving health
outcomes through research that incorporates levels of evidence for each
intended use. Both observational studies and randomized controlled
trials may be required to adequately evaluate health benefits, harms,
and costs based on returning or not returning the results of gene
variants to patients and providers. The proposed approach encourages
learning health systems to collect clinical utility evidence in a
research environment and develop the capacity for integration of
sequencing with other clinical services.14
Important implementation questions related to DNA-based population health screening need to be answered.15
These include, among others: How should screening be designed to offer
inclusive benefits for the whole population? What are the appropriate
population characteristics for screening? (e.g., age, gender). Who
should pay for DNA-based screening and clinical follow-up? How often
should data be reanalyzed? What are the clinical workforce needs related
to delivering DNA-based results and clinical follow-up at population
scale?15
Given
the relatively low frequency of individuals with genetic risk in the
population, pilot studies will require large collaboration to begin to
address some of these evidence gaps. Without large pilot studies,
opportunities to evaluate evidence of clinical utility and economic
feasibility will be delayed. There are no shortcuts on the long road to
evidence-based genomic medicine. The same can be said about any
population screening program. It is sobering to note that the now
well-established population screening for colorectal cancer took several
decades to lead to an evidence-based recommendation.11
DNA-based screening is a relatively new approach for identifying
disease risks, and it has the potential to become a population screening
program in the years ahead. While we may not be ready for
population-based DNA screening, the ACMG guidance documents represent a
leap forward in acknowledging the reality on the ground that such
screening may already be happening, with or without evidence of clinical
utility. The two documents represent a valiant effort in providing
guidance and points to consider to health-care organizations, providers,
and individuals considering DNA-based screening but should not be
construed to imply that we are ready for population-based screening.
These efforts should be conducted in the context of research enterprises
and learning health systems, which have already started in multiple
locations around the country. A collaborative approach will provide a
faster approach to answer important outstanding questions of utility and
implementation. We hope that collaborative studies including cohort
studies and clinical trials can be adequately resourced and vigorously
pursued.
Finally, more efforts are needed to engage public health
systems, professional societies, and health-care organizations in the
dialogue around DNA-based population screening. The two ACMG documents
provide a great starting point for awareness and integration of this
rapidly changing practice landscape.
Zdroj: web
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Artificial life made in lab can grow and divide like natural bacteria
SYNTHETIC cells made by combining components of Mycoplasma
bacteria with a chemically synthesised genome can grow and divide into
cells of uniform shape and size, just like most natural bacterial cells.
In 2016, researchers led by Craig Venter at the J. Craig Venter
Institute in San Diego, California, announced that they had created
synthetic “minimal” cells. The genome in each cell contained just 473 key genes thought to be essential for life.
The cells were named JCVI-syn3.0 after the institute and they were
able to grow and divide on agar to produce clusters of cells called
colonies.
But on closer inspection of the dividing cells at the time, Venter
and his colleagues noticed that they weren’t splitting uniformly and
evenly to produce identical daughter cells as most natural bacteria do . Instead, they were producing daughter cells of bizarre shapes and sizes.
“[The creators of JCVI-syn3.0] had thrown out all the parts of the
genome that they thought were not essential for growth,” says Elizabeth
Strychalski at the US National Institute of Standards and Technology.
But their definition of what was necessary for growth turned out to be
what was needed to make beautiful colonies growing on an agar plate, she
says, rather than what was needed to produce cells that divide in a
uniform and lifelike way.
By reintroducing various genes into these synthetic bacterial cells
and then monitoring how the additions affected cell growth under a
microscope, Strychalski and her team were able to pinpoint seven
additional genes required to make the cells divide uniformly.
When the researchers added these seven genes to JCVI-syn3.0 to
produce a new synthetic cell, they found that this was enough to restore
normal, uniform cell division and growth.
Strychalski and her colleagues found that while two of the seven
genes were already known to be involved in cell division, five were
previously without a known function. “It was surprising,” she says.
“Those five genes were outside the scope of what we had known about,”
says James Pelletier at the Massachusetts Institute of Technology, a
co-author of the study.
“The minimal cell has many genes of unknown function that, although
we have no idea what they do, they are necessary for the cell to live –
so that’s an exciting area for future research,” he says.
“[This research] is incredibly important for understanding how life
works and what genes are needed to operate cells reliably,” says Drew
Endy at Stanford University in California.
“Basic research on minimal cells helps us understand the principles
of the phenomena of life, and the evolutionary history of life,” says
Kate Adamala at the University of Minnesota in Minneapolis. This is
because the minimal cell is a good analogue of the last universal common ancestor of all life on Earth .
The new finding also “brings us closer to engineering fully defined,
understood and controllable” live cells, she says. “Free of the
complexity of natural live systems, synthetic cells are a tool for both
basic research and biotechnology.”
“The potential applications are vast, in agriculture, nutrition,
biomedicine and environmental remediation,” says Jef Boeke at New York
University. “The ability to correct and refine biological code like this
is a crucial step to getting us there.”
Zdroj: New Scientist
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Altered bioelectric genes give zebrafish wings like flying fish
Flying fish may have taken to the air when evolution tweaked electrical signals that control the size of their fins. This discovery suggests the existence of a previously unknown mechanism by which animals can change the relative size of specific body parts.
“How organs and tissues know when to stop growing at a certain size and stay there is a major mystery,” says Jake Daane at Northeastern University in Massachusetts. This scaling, known as allometry, is also a key driver of evolutionary change. The stunning variation in the fins of bony fish are a classic example, from the billowing veils of the tropical betta fish to the stumpy appendages of a mackerel.
Most dramatic of all are the wings of flying fish, which allow some species to leap from the sea and glide for 400 metres, the length of eight Olympic swimming pools. This helps fish evade underwater predators, a tactic so successful that it has evolved independently several times.
In comparisons of the genomes of nine species of flying fish and some non-flying relatives, Daane and his colleagues spotted genetic changes consistently associated with gliding, and uncovered sections of the genome being conserved by natural selection.
The team also studied mutations affecting fin size in zebrafish, which have short fins suited to streams and ponds. This is unlike flying fish, which have expanded their paired fins – equivalents of our arms and legs – into wings to take flight.
The zebrafish work revealed two interesting gene variants: one affecting how potassium ions flow into cells, which made all the fins larger; the other affecting how cells absorb compounds called amino acids, which made all the fins smaller. Neither affected the overall body size of the fish.
Similar genes and cellular processes involving them showed up in the flying fish genomes. But this didn’t explain why only their paired fins are overgrown.
So the team combined both gene variants in one zebrafish, and found that only the paired fins were overgrown, transforming the zebrafish into a copy of a flying fish.
Potassium ion flow affects how electrical charge moves over tissues, which affects embryonic development – including fin growth – and tissue regeneration. But the exact mechanism is poorly understood, and it is unclear how amino acid uptake could tweak bioelectricity to create such specific changes in fin size.
Combining lab genetics with the comparison of genomes is a very creative approach to unpick the mechanisms behind allometry, says Peter Currie at the Australian Regenerative Medicine Institute in Melbourne. Understanding how evolution generates shape and form will aid research into how tissues regenerate, he says. “The more you understand about the evolutionary processes that guide the formation of structures, the more you’ll be able to understand and to use in [medicine].”
Zdroj: New Scientist
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First million-year-old DNA extracted from Siberian mammoth teeth
For the first time, preserved DNA has been recovered from animal remains over a million years old. The DNA belonged to two mammoths that lived around 1.2 million years ago.
The genetic sequences change our understanding of mammoth evolution. They reveal that, at that time, Siberia was home to two distinct groups of these animals. The mammoths of North America were the product of a hybridisation event between these two groups, and obtained half of their DNA from each.
“Instead of there being one species [or lineage] of mammoth up in Siberia around 1-2 million years ago, it now looks like there are two,” says Love Dalén at the Centre for Palaeogenetics in Stockholm, Sweden.
The first mammoths evolved in Africa about 5 million years ago. “It was originally a tropical species,” says Dalén. But over the next few million years, some mammoths moved out of Africa.
A key species was the steppe mammoth (Mammuthus trogontherii ), which evolved in northern Eurasia about 1.7 million years ago. Later, North America was home to Columbian mammoths (Mammuthus columbi ). The famous woolly mammoths (Mammuthus primigenius ) lived in Eurasia more recently, with the last ones dying out just 4000 years ago .
Quite how these species are related, and why they evolved in the ways they did, are tricky questions to answer.
Dalén’s colleague Patrícia Pečnerová, now at the University of Copenhagen in Denmark, extracted DNA from three mammoth teeth found in north-east Siberia. They were collected in the 1970s by the late Russian palaeontologist Andrei Sher . Two of the teeth, from Krestovka and Adycha, look like they belonged to steppe mammoths and are respectively 1.1-1.2 and 1-1.2 million years old. The third, from Chukochya, seems to be a woolly mammoth and is 500-800,000 years old.
The older teeth are the first specimens greater than a million years old to have their DNA read. That is far older than the previous record for ancient DNA, a 700,000-year-old horse , although it has proved possible to obtain protein sequences from even older remains, including a 1.9-million-year-old Homo erectus tooth .
“This looks supercool,” says Rebekah Rogers at the University of North Carolina at Charlotte. “It’s bringing together palaeontology and genetics on a deeper timescale than ever before.”
The team found that the Adycha and Chukochya teeth both looked like ancestors of the later woolly mammoths. But the Krestovka tooth was a surprise. Despite being about the same age as the Adycha one, its DNA was quite different. The mammoth it belonged to was a member of a separate lineage that branched off from the other Eurasian mammoths at least 1.78-2.66 million years ago.
Dalén’s team believes that the Krestovka mammoths were the ones that first colonised North America, crossing a land bridge to what is now Alaska perhaps 1.5 million years ago. “According to our model, the mammoths in North America between 1.5 and 0.5 million years ago were exclusively this Krestovka type,” says Dalén.
But the later Columbian mammoths of North America, whose DNA had previously been sequenced, weren’t simply the descendants of the Krestovka mammoths. Instead, the story took a twist. In Siberia, the steppe mammoths gradually gave rise to woolly mammoths. Much later, “a small band of woolly mammoths crossed the Bering land bridge and entered North America, and there they hybridised with the rest of the Krestovka mammoths”, says Dalén.
The result was Columbian mammoths, which were a 50:50 mix of Krestovka and woolly mammoth ancestry.
Such interbreeding seems to be common in the origin of new species, says co-author Tom van der Valk at Uppsala University in Sweden. “This is one of the major things that has changed in the past decade when we talk about speciation. It seems more and more, whenever we look, we do find gene flow between lineages that have been separate for some time and then intermixed again.”
“What this piece of work is showing is that biology is messy,” says Tori Herridge at the Natural History Museum in London. The formation of a species is rarely as simple as a population splitting in two, she says.
The analyses also shed new light on the evolution of woolly mammoths.
Previously, it was assumed that these animals evolved thick coats and other adaptations in response to the cold climate of the ice age. “It’s always seen as the epitome of cold-adapted mammoths,” says Herridge.
But the DNA shows that many of the woolly mammoth’s adaptations to the cold were already present in the earlier steppe mammoth populations. “It has been more of a gradual process, slowly getting better at this environment, rather than one rapid, single burst of adaptation,” says van der Valk.
This means we may need a new explanation for the evolution of some woolly mammoth traits, says Herridge. “Maybe the cold adaptation is not the main driver.”
Zdroj: New Scientist
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Feng Zhang interview: CRISPR can fight covid-19 and climate change
IT IS no exaggeration to call Feng Zhang one of the most groundbreaking scientists working today. In his 20s and 30s, he helped develop two revolutionary technologies. The first, known as optogenetics, involves inserting genes into brain cells to allow them to be switched on and off by shining a light on to them. This technique has helped us understand how the brain works and is being explored as a potential treatment for some neurological conditions.
The second, CRISPR , is a gene-editing technology that promises to correct a near-limitless list of human diseases . These days, Zhang has a dual appointment at the McGovern Institute for Brain Research and the Broad Institute, both in Massachusetts, and is often spoken of as a future Nobel laureate.
Powerful tools can be used in different ways, however, and when it comes to CRISPR, there have already been some worrying developments. Two years ago, biophysicist He Jiankui was widely criticised – and eventually handed a prison sentence – for using CRISPR to gene edit human embryos. Many researchers, including Zhang, feel his actions were an ethical overstep.
Meanwhile, Zhang is party to an ongoing dispute over who should own the patent for CRISPR. Other scientists were first to publish details of the technology, but he was quickest to show it works in human cells.
New Scientist caught up with Zhang to discuss those controversies and to get the low-down on the future of CRISPR. These days, Zhang is optimistic that the technology may help us in the battle against covid-19 and that it may have applications that go far beyond medicine.
Jessica Hamzelou: What are the most promising applications of CRISPR in the works today?
Feng Zhang: One of the tantalising possibilities is to use it to correct DNA sequences so that we can restore genes and treat disease. I co-founded Editas Medicine with several other colleagues and, earlier this year, the company began human trials using CRISPR to treat a rare, inherited eye disease called Leber congenital amaurosis. A harmless virus carrying the CRISPR tools is injected into the eye, where it modifies cells to restore normal function of a faulty gene.
Another company called CRISPR Therapeutics has been using the system to treat people who have beta thalassaemia, a disorder in which the blood has low levels of haemoglobin. They found that one patient responded very well and no longer needs blood transfusions .
Because you can use CRISPR to target many genes at once in human cells, scientists have been using it to carry out screens to find genes that are involved in specific disease processes . Then we can potentially edit those genes too.
So CRISPR is already showing promising results. How does it make you feel when you see that?
It is really exciting to be part of building something that can have a huge impact on people’s lives, but it also makes me realise that there is a lot more that we need to do. Seeing these promising early results really motivates me to want to do more.
What needs to be done before these become approved treatments?
We need to make CRISPR work more efficiently and precisely. One risk is that it will not only make edits that you want, but, by random chance, it also edits something else. We have started on this by engineering new versions of the system that are much more specific. We also need to develop the tools so that they can make many more types of changes in the genome and influence how genes work in different ways.
We are also working on new ways to deliver the CRISPR enzymes. We have developed a protein from Staphylococcus aureus bacteria, which is much smaller than the first CRISPR system we reported. The more compact the package is, the easier it should be to get it inside cells where it can do its work. We have already found that this system can edit genes efficiently in mice.
Are there any conditions that you are particularly interested in?
I have had an interest in mental illness and psychiatric conditions since I was a college student. People around me have been affected by these illnesses. CRISPR is already being used to better understand how they affect the brain and how we might develop more effective treatments.
But all diseases are important. Each affects people in different ways, biologically, but also emotionally. In terms of negatively affecting their lives, it’s the same – it is a toll on people’s quality of life. This is why I have focused on developing the technology for gene editing as a broadly applicable platform.
You are involved in a patent dispute over CRISPR. Does it matter who owns the rights to the technology, as long as it is being used for good?
It is important that this technology is developed safely and responsibly, and shared in a way that everyone can benefit from. The patent holder has the privilege and obligation to ensure that the technology is made accessible. The Broad Institute will continue to do this.
What do you think the next breakthroughs are going to be?
We will continue to see a lot of exciting applications in therapeutics. Cell therapy, where clinicians take cells out of a patient, repair them, and put them back, has a lot of potential. Integrating CRISPR with other technologies, like stem cells , could be especially powerful. These approaches could be used in everything from blood diseases all the way to liver, muscle and brain diseases in future.
One possible way to do this is to use stem cells to derive microglial cells, which are brain cells that respond to infections and damage. These cells could be engineered to restore or introduce genes. You could then transplant them into patients so that they can take residence in the brain and treat conditions. In the long run, we might treat neurodegenerative diseases in this way.
Have there been any uses of this technology that have worried you?
Absolutely. One of the things I was very concerned about was the use of CRISPR in editing human embryos. Less than two years ago, scientists described using CRISPR to edit two human embryos and then using them to create two genetically modified babies. I think it crossed many ethical bounds.
There has been lots of talk about how to regulate the technology, both before and after that incident. How should we do that?
I have been involved in a number of discussions about this, but the world is complicated. There isn’t a single type of ethics or culture or governing system. This means we have to reach agreements through international collaborations. People must come to an understanding of the potential impacts of these technologies before we get a consensus on using them.
The technology is still nascent and there is much about its performance and safety that we don’t fully grasp. To jump ahead and begin to apply this to a modified human embryo could have unintended consequences. On top of that, we don’t understand the biological mechanism that causes a lot of things that we want to treat. So, even if the technology was perfect, we wouldn’t know what edits to make to the genome. This is why we can’t yet use CRISPR to treat conditions like Alzheimer’s or cancer.
There are also tangled issues surrounding consent. Who has the right to consent to the use of this? How will availability of these technologies affect the human race going forward? When people think of changing the genome, they often think of genetic enhancement. We’ve all seen enough dystopian science fiction to know that a society like that would be terrible for humanity.
What do you think gene-editing technologies will look like in 10 years?
We will probably begin to see the technology applied to diseases that affect a large number of people, like cancer or even brain conditions. I suspect gene editing will be used beyond medicine, for example in agriculture, to create more drought-resistant and higher-yielding crops to help fight global hunger. We might also see CRISPR used in biological computing or as part of the response to climate change.
How could the technology help with climate change?
Some scientists are working out how to use CRISPR to engineer plants so that they can sequester more carbon. Others are looking at ways to engineer fast-growing cells like cyanobacteria to get them to take in and store carbon faster. These are some starting ideas to tackle climate issues. I am sure people will use their creativity to come up with more.
We can’t afford to ignore the climate, but we also have a pandemic to deal with. Can CRISPR help with that?
My team has spent a lot of time developing CRISPR-based diagnostics. One of the critical things for helping us fight the covid-19 pandemic is the ability to test more people , more rapidly and in more places in the community . So we have been working on something we called the STOPcovid reaction . The main advantage of a CRISPR-based test is that it doesn’t require sophisticated laboratory equipment – you just need a water bath at 60°C. You put your sample vial into the water bath and then, within an hour, you can dip in a test strip and get a result.
How soon will it be ready?
Another company I helped found, called Sherlock Biosciences, has been developing similar CRISPR-based technology for detecting coronaviruses. In May, this received emergency use authorisation from the US Food and Drug Administration. So now people in clinical labs in the US can begin to use that technology for detecting coronavirus, which should help expand our testing capacity.
My lab has also distributed STOP covid test kits around the world. One of our collaborators in Thailand got approval from the Thai government to use it in his hospital and will be screening surgery patients for coronavirus, so that they can better triage and isolate people who test positive for the virus.
You were also involved in the invention of optogenetics , another groundbreaking discovery. What is your secret to spotting the next innovation?
I am always curious about the way things work – or don’t work in the way they should. I have those questions in mind whenever I think or read about something. I always cross-check with the scientific problems I am interested in and see whether I can create a new connection.
The other thing I do is look at nature, which has done way more than we can imagine. CRISPR proteins are examples of things that nature has created through billions of years of evolution that have amazing applicability.
Also, when I was growing up, my parents always told me that I should make myself useful and not waste time. That probably has something to do with it.
Zdroj: New Scientist
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Russian biologist still aims to make CRISPR babies despite the risks
Russian biologist Denis Rebrikov has told New Scientist that he still plans to use CRISPR genome editing to prevent children inheriting deafness, despite a major international report out today saying it isn’t yet safe enough to try in people. “We are still planning to correct the inherited hearing loss mutation in [the gene] GJB2, so that a hearing baby is born to a deaf couple,” says Rebrikov, who is at Pirogov Medical University in Moscow. Three children whose genomes were altered by CRISPR gene editing were born in China in 2018 and 2019. The unauthorised creation of those embryos caused concern around the world and spurred scientific institutes to set up the International Commission on the Clinical Use of Human Germline Genome Editing, a group of 18 doctors, biologists and ethicists from 10 countries tasked with drawing up guidelines for how to proceed in a responsible way. The main conclusion of its report, out today, is that genome editing isn’t yet safe and effective enough for altering human embryos before implantation in the uterus. “The criteria for safe and effective heritable human gene editing have not yet been met,” says Haoyi Wang at the Chinese Academy of Sciences, who is on the commission. The reason is that existing methods can cause unintended genetic mutations and also may not correct the condition-causing mutation in every cell, an issue known as mosaicism. However, the technology is advancing so fast that it might be ready for use in just a few years, says Wang. These problems aren’t a deal-breaker for using CRISPR as a treatment for serious conditions such as cancer or sickle cell, as the potential benefits outweigh the risks, and the changes CRISPR makes in these cases are not heritable. Many trials are already under way. However, there is widespread agreement that it isn’t yet safe enough to use CRISPR to make heritable changes by editing human embryos – with Rebrikov being one of the few exceptions. He told New Scientist last year that he plans to use to CRISPR to correct a recessive mutation in the GJB2 gene that causes deafness. Almost all genetic conditions can already be prevented by screening IVF embryos before implanting them, known as preimplantation genetic diagnosis, or PGD. When both parents are deaf because of a GJB2 mutation, however, all their children will be deaf too; PGD isn’t an option. When asked to comment on the commission’s report, Rebrikov confirmed that he still plans to go ahead. He didn’t mention the safety issue. Nor is it clear if Rebrikov has any official approval for his plans. In October 2019, the Russian health ministry said it would be premature to gene-edit human embryos. But, as in many other countries, there are no laws explicitly banning it. Even if CRISPR genome editing gets to the point where it is safe and effective enough for altering human embryos, its use to prevent deafness would be controversial. “I would not be supportive of it being used first for deafness,” says Sarah Norcross at the Progress Educational Trust, a UK charity to advance public understanding of science. The commission’s report recommends that if any countries decide CRISPR is safe enough to use for making heritable changes, it should be limited to a few situations. First, those in which prospective parents have no option for having a genetically related child that doesn’t inherit a disease. Second, those where PGD is unlikely to succeed – that is, in situations where less than 1 in 4 viable IVF embryos would be free of the condition. Even so, the report recommends that couples should have attempted at least one cycle of PGD without success. Rebrikov’s plans do meet these criteria, but the report also recommends that heritable genome editing should initially be limited to serious conditions caused by a mutation in a single gene. “My model is hereditary hearing loss, so, this can ‘be limited to serious single-gene diseases’, I guess,” says Rebrikov. However, the report defines a serious single-gene condition “as one that causes severe morbidity or premature death”. Many would argue that this definition excludes deafness. While Norcross doesn’t support Rebrikov’s stance, she and others are critical of the report’s recommendations for initial uses. “It does seem rather narrow,” she says. For instance, Norcross doesn’t agree with the recommendation that couples should have already tried PGD at least once. “PGD is not easy, and it’s not necessarily available,” she says. “The woman’s age does not stop while all this is going on.” Nor does Norcross think the initial uses need to be limited to single-gene conditions. “It’s not necessarily irresponsible to make two edits,” she says. Many conditions are caused by multiple mutations, and PGD is of little use for preventing these.
Zdroj: New Scientist
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Supergenes play a larger role in evolution than previously thought
Large blocks of 'plug and play' genes play a super-sized role in adaption-and may help fill lingering gaps in Darwin's theories
Resources at Genome BC. "A convergence of vision, strategic investments, and scientific leadership has helped propel innovations in sunflower genomics research that will have significant implications for food security and continue to attract global investment to BC."
The researchers sequenced the genomes of more than 1,500 plants from three wild sunflower species: the common sunflower (Helianthus annuus), prairie sunflower (Helianthus petiolaris), and silverleaf sunflower (Helianthus argophyllus). They then looked at associations between genetic variants and more than 80 traits that they monitored throughout the plants' growth, as well as with the soil and climate of their populations of origin. The result is the largest and most comprehensive demonstration to date that structural variants--rearrangements of chromosome structure that are largely responsible for creating the supergenes in the first place--play a fundamental and widespread role in adaptation and speciation.
In addition to the supergenes, the study also identified numerous independent genes that appear to confer resistance to the environmental stresses wild sunflowers face, including drought, heat and low nutrient stress. These independent genes will be invaluable to sunflower breeders as they develop cultivars that can tolerate the more extreme growing conditions predicted under future climate change. From an agricultural standpoint, they offer more flexibility than the supergenes.
"Because they work as a package, introducing a supergene into a cultivated sunflower would mean carrying over both the beneficial and detrimental traits associated with it,' says Todesco. "While supergenes contain several genes that could be beneficial in an agricultural setting, they also contain hundreds of other genes, some of which might not be so beneficial in a crop. For example, by reducing yield or modifying the oil content of seeds."
Zdroj: web
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Three people with inherited diseases successfully treated with CRISPR
Two people with beta thalassaemia and one with sickle cell disease no longer require blood transfusions, which are normally used to treat severe forms of these inherited diseases, after their bone marrow stem cells were gene-edited with CRISPR .
Result of the ongoing trial, which is the first to use CRISPR to treat inherited genetic disorders, were announced today at a virtual meeting of the European Hematology Association.
“The preliminary results… demonstrate, in essence, a functional cure for patients with beta thalassaemia and sickle cell disease,” team member Haydar Frangoul at Sarah Cannon Research Institute in Nashville, Tennessee, said in a statement .
Beta thalassaemia and sickle cell are diseases caused by mutations that affect haemoglobin , the protein that carries oxygen in red blood cells. Those with severe forms require regular blood transfusions.
However, a few people with the disease-causing mutations never show any symptoms, because they keep producing fetal haemoglobin in adulthood. Normally, fetal haemoglobin stops being produced soon after birth.
This discovery has inspired the development of treatments based on boosting fetal haemoglobin. In this trial, run by collaborating companies CRISPR Therapeutics and Vertex, bone marrow stem cells are removed from people and the gene that turns off fetal haemoglobin production is disabled with CRISPR.
The remaining bone marrow cells are killed by chemotherapy, then replaced by the edited cells. This is done to ensure new blood cells are produced by the edited stem cells, but the chemotherapy can have serious side effects including infertility.
The first two patients with beta thalassaemia no longer need blood transfusions since being treated 15 and 5 months ago. Nor does the patient with sickle cell disease, 9 months after treatment.
The results are excellent, says Marina Cavazzana at the Necker-Enfants Malades Hospital in Paris, France, whose team has treated a 13-year-old boy with sickle cell disease using a different approach .
While the three patients did suffer some adverse effects due to the chemotherapy, the CRISPR gene editing appears safe. However, the patients may need to be monitored for the rest of their lives to be sure it has no adverse effects, says Cavazzana.
Altogether five people have now been treated. The trial was put on hold because of the coronavirus pandemic, but has now resumed.
Zdroj: New Scientist
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Happy DNA Day: 11 Facts about Genetic Engineering and Why It's Important
Genetic engineering is a very powerful and important weapon in our technological arsenal. Here is why.
Genetic engineering is one of the most important developments in human history. Controversy and ethical concerns aside, the ability to manipulate the very genetic code of organisms is a very powerful tool.
With modern techniques like CRISPR , genetic engineering could, very well, allow us to cure any diseases in the future, or produce crops with yields hitherto only ever dreamed of . We may even be able to bring back long-extinct animals .
Let's just make sure we take note of the warnings of Michael Crichton from his "Jurassic Park" novels.What are some interesting facts about genetic engineering, and why it is important?
So, without further ado, here are some interesting facts about genetic engineering and why it is important. This list is far from exhaustive and is in no particular order. 1. The first genetically modified animal was created in 1973 The very first genetically modified organism, GMO for short, was actually a bacteria back in 1973. This new strain of E. coli bacteria was altered to become resistant to the antibiotic kanamycin .
Mice became the first animal to be genetically modified around the same time.
Insulin-producing GMO bacteria became a thing in 1982 and were quickly commercialized. GMO plants for food have actually been around since 1994, including many varieties of edible crops.
2. Genetically engineered things are actually all around us Genetic engineering techniques are used widely today for research, agriculture, industrial biotechnology, and medicine. For example, genetically modified enzymes used in laundry detergent or medicine like insulin and human growth hormone can now be readily created in GMO cells.
Genetic engineering is, in effect, all around us today.
3. Some of the most common genetic engineering test subjects are mice and zebrafish Some of the most common animal test subjects for genetic engineering are mice and zebrafish. Both have relatively short lifespans, and so any modifications to their DNA can be assessed very quickly in the growing animal. Zebrafish are particularly useful as their larval phase is, more or less, completely translucent. This allows researchers to easily see what's going on inside the infant fish as a result of genetic modifications made.
4. Genetic modification is something of an ethical dilemma While the practical benefits of genetic engineering are readily demonstratable, there are some ethical and ecological concerns around them. For example, genetic modification of human embryos is, rightfully, considered unethical.
With regards to ecology, it has been argued that GM organisms, if ever released into nature, could readily outcompete wild organisms. This could be devastating for natural habitats and species.
Others disagree .
5. GM researchers can build completely synthetic genomes Genetic engineering has come a long way since the 1970s. Today, researchers can actually build a long base cheaply, and accurately on a large scale.
This allows GM researchers to be able to conduct experiments on genomes that don't actually exist in nature. Called synthetic genomics , this field of study is really finding its stride.
Some companies, like Synthetic Genomics , have even been founded to study potential commercialization opportunities from custom designed genomes.
6. GM scientists can even build complete chromosomes in the lab Further to the above, genetic engineers can, today, create entirely synthetic chromosomes in the lab. For example, the first synthetic chromosome for yeast was created only a few years ago.
This is considered a very big deal in the field of synthetic biology.
7. Genetic engineering can be used on any kind of organism As we have seen, a wide swathe of organisms can be altered using genetic engineering. This can range from anything from a lowly virus to an entire sheep.
8. Genetically modified animals are helping with some very serious human diseases and disorders As we have already touched on, genetic engineering is being used to treat some very serious human diseases and disorders like diabetes with insulin. But it is also being put to work providing therapeutic solutions for other serious health issues like Alzheimer's and cystic fibrosis.
9. Genetic engineering is a very sophisticated form of cut and paste As we have already touched on, genetic engineering is being used to treat some very serious human diseases and disorders like diabetes with insulin. But it is also being put to work providing therapeutic solutions for other serious health issues like Alzheimer's and cystic fibrosis.
10. Genetic engineering, as a term, used to be broader in its definition While today, genetic engineering really only applies to recombinant DNA techniques, it used to mean something a little different. Prior to the advent of these techniques, this term used to encompass less sophisticated things like artificial selection, artificial insemination, in-vitro fertilization, and cloning.
11. Recombinant DNA techniques were first developed in the late 1960s Modern genetic engineering all kicked off back in the late 1960s. This was largely thanks to the discovery of restriction enzymes in 1968 by Swiss microbiologist Werner Arber.
So-called type II restriction enzymes were discovered shortly after by the American microbiologist Hamilton O. Smith .
The former was found to be able to clear DNA at random locations, while the latter could be used to target a specific site.
Zdroj: Interesting Engineering
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Why Does Covid-19 Make Some People So Sick? Ask Their DNA
Consumer genomics company 23andMe wants to mine its database of millions
of customers for clues to why the virus hits some people harder than
others.
SARS-CoV-2, the pandemic coronavirus
that surfaced for the first time in China last year, is an equal
opportunity invader. If you’re a human, it wants in. Regardless of age,
race, or sex, the virus appears to infect people at the same rate . Which makes sense, given that it’s a totally new pathogen against which approximately zero humans have preexisting immunity.
But the disease it causes ,
Covid-19, is more mercurial in its manifestations. Only some infected
people ever get sick. Those who do experience a wide range of symptoms.
Some get fever and a cough. For others it’s stomach cramps and diarrhea.
Some lose their appetite. Some lose their sense of smell . Some can wait it out at home with a steady diet of fluids and The Great British Baking Show. Others drown in a sea of breathing tubes futilely forcing air into their flooded lungs. Old people, those with underlying conditions, and men make up the majority of the casualties. But not always. In the US, an alarmingly high fraction of those hospitalized with severe symptoms are adults under the age of 40. Kids, and in particular infants, aren’t invincible either .
To understand what accounts for these differences, scientists have been scouring the patchy epidemiological data
coming out of hotspots like China, Italy, and the US, looking for
patterns in patients’ age, race, sex, socioeconomic status, behaviors,
and access to health care. And now, they’re starting to dig somewhere
else for clues: your DNA.
On Monday, 23andMe
launched a new study intended to illuminate any genetic differences
that might help explain why people who’ve contracted Covid-19 have such
varying responses to the infection. The consumer genomics company joins a
number of emerging academic projects aimed at answering the same
question. Prior research indicates that some gene variants can put
people at higher risk for certain infectious diseases. Others offer
protection, like the CCR5 mutation
that makes people who carry it resistant to HIV. At this point, it’s
too early to say how big a role DNA might play in vulnerability to
Covid-19. But these findings may one day be used to identify people with
higher risk for the most serious symptoms and to sharpen the search for
potential new treatments .
“We
want to understand how your genes influence your response to the
virus,” says Joyce Tung, 23andMe’s vice president of research. “Our hope
is that by collecting data from people who’ve been tested and diagnosed
with Covid-19, that we can learn something about the biology of the
disease that we can contribute to the scientific community to help them
treat people more successfully.”
While other at-home DNA testing companies have converted their shuttered labs into Covid-testing operations ,
23andMe decided to leverage a unique asset: its database of more than
10 million customers, 80 percent of whom have given consent for their
genetic information and other self-reported details
to be used for research. The company has spent years building out a
platform that makes it easy to push out surveys en masse to this trove
of potential study participants. As a result, each genetic profile comes
with hundreds of phenotypic data points—like how many cigarettes a
customer has smoked in their lifetime or whether anyone in their family
has ever been diagnosed with diabetes. The sheer volume of data that
23andMe has at its disposal has powered the company’s leap into drug discovery , and made it a genetic research publishing powerhouse .
The
latest survey to go live on 23andMe’s customer portal asks questions
about where people live, what kinds of social distancing they’ve been
doing, and whether or not they have been tested for, diagnosed with, or
exposed to Covid-19. (The survey is only open to 23andMe customers in
the US.) Company officials hope to enroll hundreds of thousands of
customers in the study, including those who have tested positive, those
who have tested negative, and those who have experienced flulike
symptoms but not yet been tested—as well as those whose family members
have experienced infections. People who have tested positive will
receive a follow-up survey about the severity of their symptoms and
whether or not they were hospitalized, according to Adam Auton, a
principal scientist at 23andMe who is heading up the new Covid-19 study.
Anyone who participates will get invited back each month to answer more
questions, so 23andMe can capture any new cases that develop among this
cohort over time.
If the company collects enough responses from
people who’ve contracted Covid-19, 23andMe’s research team will conduct a
statistical analysis called a GWAS, or genome-wide association study. A
mainstay of genetic research, GWAS involves sorting people into
different groups—in this case probably based on symptoms—and scanning
their DNA data to see if certain single-letter variations in the genetic
code show up more often among people with certain symptoms. If that
happens a significant number of times, they can say with some confidence
that those variants are linked to those symptoms.
It’s
hard to predict what sorts of genes will get unearthed during these DNA
mining expeditions, but many of them will likely map back to regions of
the genome responsible for orchestrating the body’s immune response,
says Michael Snyder, chair of the genetics department at Stanford
University, who is not affiliated with the 23andMe research. “In
general, we know that genetics do influence the course of a viral
infection,” he says. That’s to be expected, he adds, given that over
history humans evolving in different environments have been exposed to
distinctive pathogens. “It’s logical that immune systems are tuned
differently inside different people,” he says. (In fact, a dangerous
immune overreaction known as a cytokine storm caused the deaths of many SARS patients and is suspected to be responsible for some of the fatalities among young Covid-19 patients.)
Another potential candidate is the gene that codes for the ACE2 receptor .
Found on the surface of lung and other human cells, it’s the molecular
doorway through which SARS-CoV-2 infiltrates the body. Small variations
in this gene may result in versions of the receptor that are easier or
more difficult to unlock. Alternatively, variations in the regions of
the genome that turn the ACE2 gene on or off might also play a role.
Less gene activity would mean the person’s cells have produced fewer
receptors for the virus to grab onto.
At this point, it’s too
early to venture guesses about the role genes play in determining
Covid-19 outcomes, says Snyder. But he is willing to bet that projects
like 23andMe’s probably won’t turn up a single genetic variant that
determines whether or not someone winds up in the intensive care unit.
“I’d be surprised if they find anything as strong BRCA,” he says,
referring to one of the most powerful cancer predictors scientists have discovered; mutations in BRCA genes quadruple a person’s likelihood of getting certain forms of breast cancer.
That’s
because GWAS is a numbers game. It’s best at identifying mutations that
occur over and over again throughout a population, with each exerting
only a very small effect on an individual person’s disease
susceptibility. And because GWAS are usually performed on the kind of limited genetic data
23andMe collects—a snapshot of about 600,000 locations in the
genome—these common variants are easier to pick out than rare ones.
But
it’s these very rare mutations that are likely driving cases of extreme
susceptibility to Covid-19, says Stephen Chapman, a respiratory
physician and researcher at the University of Oxford’s Wellcome Trust
Centre for Human Genetics, who isn’t part of the 23andMe project. In the
mid-2000s, he conducted some of the first genetic studies on
susceptibility to bacterial pneumonia, and discovered rare mutations in
immune-related genes that made otherwise healthy children and adults
especially susceptible to an invasion by one particular bacteria.
Chapman suspects similarly rare mutations involved in immune function or
inflammatory responses could be what’s putting young, apparently fit
adults without other risk factors into ICU beds. “This is the major
drawback of GWAS, in my view,” he says. “It will miss those rare,
causative mutations.”
Finding
them will require collecting blood from these extreme outliers and
sequencing their entire genomes. Decoding the DNA from young adults
strapped to ventilators might reveal a unique genetic vulnerability to
Covid-19. Conversely, DNA from the octogenarians who’ve tested positive
for Covid-19 but experienced no symptoms might contain protective
mutations to the worst forms of the disease.
More
than 90 such sequencing projects are already underway in academic labs
around the world, as scientists have raced to understand a disease whose
global death toll has now surpassed more than 76,000 . Some are existing population genetics studies that follow thousands of volunteers for years, like the UK Biobank .
DeCODE Genetics, an Icelandic company that has been collecting genome
and health data on the island nation’s 364,000 inhabitants for decades , has also received government permission to release its Covid-19 testing results, according to Science .
Others are new studies dedicated solely to Covid-19 patients. To pool
all the genetic data streaming in from these various projects,
researchers at the University of Helsinki recently launched a central
clearinghouse called the Covid-19 Host Genetics Initiative .
With more data comes more statistical power, increasing the hope of
finding mutations that might alter a person’s experience of the new
disease, as well as the course of humankind’s battle against it.
But
don’t expect to get a genetic scorecard for Covid-19 risk anytime soon.
Chapman says the most likely outcome of all these studies won’t be
having the ability to identify more susceptible people based on their
DNA. Rather, it will be a better understanding of the molecular pathways
involved in severe forms of Covid-19. “With a new, devastating human
disease, there is an urgent need to understand the biology,” says
Chapman. Mapping the genes that direct different immune responses may
reveal targets for novel therapies or help doctors provide more tailored
care to individual patients. “Both GWAS and whole genome sequencing
approaches can play a valuable role here,” says Chapman.
Age,
underlying health problems, access to early testing and quality
care—these things will matter most of all in determining who lives and
who dies from Covid-19. But DNA almost certainly plays a role in shaping
disease outcomes. And there’s still everything left to learn about it.
Zdroj: web
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RNA Gene Fragments of the COVID-19 Virus Found in Incoming Dutch Sewage Water
Microbiologists at research institute KWR revealed on Monday that they found RNA gene fragments of the COVID-19 virus in incoming sewage water at the Dutch WWTP. The fragments were discovered before any coronavirus cases were reported indicating the sewage water can serve as an early warning system.
Professor Rosina Girones, Research Group Leader at the University of Barcelona, and Professor Gertjan Medema, Principle Microbiologist at KWR shared their findings in a webinar.
They revealed that, although it’s unlikely that sewage will become an important route of transmission, the COVID-19, coronavirus is indeed secreted in a person's stools and can be found in sewage water.
“It is important to collect information about the occurrence and fate of this new virus in sewage to understand if there is no risk to sewage workers, but also to determine if sewage surveillance could be used to monitor the circulation of SARS-CoV-2 in our communities,” Medema, wrote in a paper released ahead of peer review.
Early warning system
Detection of the virus in sewage systems could serve as an indication that the virus is emerging, argued Medema.
“That could complement current clinical surveillance, which is limited to COVID-19 patients with the most severe symptoms. Sewage surveillance could also serve as an early warning of (re-)emergence of COVID-19 in cities, much like the sewage surveillance for poliovirus that has been used for this purpose" added Medema.
In the webinar, Medema also revealed that for the time being the limited evidence they have indicates that the virus is not robust in wastewater and it does not pose a threat to sewage workers. His advice was for workers to use standard personal protection.
"We don't think that this is an important waterborne pathogen. We think that the primary routes of transmission are the ones that we have heard about: the air droplets from people that are coughing or sneezing and maybe contaminated surfaces," said Medema.
Zdroj: Interesting Engineering
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Scientists Use CRISPR to Delete Fearful Memories in Rats
The practice could be used to treat memory-related disorders such as PTSD and drug addiction.
Ah, Memories! They can be some of our best assets or our most painful tormentors. Good memories give us a sensation of warmth and hope for better times, but bad memories can cause serious trauma.
But what if you could delete all unpleasant memories? Would you take that option, or do you believe that even the bad memories are part of who you are? Well, the possibility to remove bad memories is becoming all-the-more plausible, and it could soon become a reality.
Researchers at Peking University have used CRISPR gene editing to 'delete' memories from rats. More specifically, they removed fearful memories from their test subjects.
Yi Ming, one of the paper’s co-authors, told Ecns.cn that the new technique could be used to treat pathological memories and memory-related conditions such as PTSD, drug addiction, chronic pain, and chronic stress. Ming acknowledged that negative memories could be essential for survival, but when too much focus is given to them, they cause psychological and physical disorders.
A tricky practice The study was published in Science Advances and leads to some tricky ethical questions. In many ways, our memories shape us. Therefore losing some of them, even the painful ones, could change us fundamentally.
Another question is how the researchers would decide which memories to delete and which to keep. The process does not make clear how those memories are targeted. Could the researchers really get the right memory to cut, or might they remove a subject of another memory, perhaps a desired one?
Although at first glance, the practice does seem to have some merit, particularly in treating psychological disorders, it is one that has to be undertaken with caution.
The study does not clarify how memories are targeted and what safety measures are taken to ensure that memories essential to one's survival and identity are not accidentally accessed and deleted. This indicates that much work still needs to be done before the CRISPR treatment becomes a viable practice.
Zdroj: New Scientist
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Consumer Genomic Testing in 2020
Consumer genomic testing (CGT) can be defined as DNA tests sold or marketed directly to consumers for recreational, ancestry-related, or health-related purposes. Direct-to-consumer (DTC) testing does not typically involve a health professional in the selection of testing and return of test results, whereas consumer-driven genomic testing may involve a physician or other health professional who could have a financial relationship with the testing company. CGT has been part of the landscape of biomedicine for several decades.1 The earliest examples of these tests included DNA testing of a small number of single-nucleotide variations (SNVs) associated with nutritional status, drug metabolism, and mental health risk. Some of these tests were controversial; for example, tests that measured SNVs to predict risk of developing depression were criticized by geneticists, ethicists, and government regulators.2
Over time, CGT has become considerably more complex, including tests such as SNV arrays and genome sequencing, in which millions of variations can be detected simultaneously. CGT has also moved closer to providing testing similar to services offered by clinical laboratories. In 2017, the US Food and Drug Administration granted authorization to a single company to offer health-related DTC genetic tests for risk of multiple health conditions, including Alzheimer disease, Parkinson disease, and α1 -antitrypsin deficiency. Since then, additional authorizations for pharmacogenomics testing and cancer risk have been granted.3 If estimates that by 2021 more than 100 million people worldwide will have undergone CGT prove true, it seems likely that more adults will have had their DNA tested outside of the traditional health care system than within it.4 Although this presents an opportunity for the increased appropriate use of genomic information in health, the influx of CGT results also poses challenges for clinicians and their patients.
In 2019, the National Academies of Sciences, Engineering, and Medicine Roundtable on Genomics and Precision Health conducted a workshop to explore the current landscape of CGT, including consumer drivers for the uptake of CGT, how CGT may affect traditionally underserved and minority populations, integration of CGT into health systems, and the policy and regulatory issues of this rapidly evolving field.5
The increase in CGT uptake over the past several years may be attributed to a variety of factors, including marketing, declining testing costs, and an increasing perception that CGT provides health value. Perhaps less obvious are 2 additional factors. First, CGT companies are increasingly intermixing low-cost health-related CGT with ancestry-related CGT. This is exemplified by a 2019 announcement by Ancestry to launch health-related testing as one of its products and by 23andMe bundling ancestry and health testing services into a gift package costing less than US $100 for the 2019 holiday season. Some marketing of ancestry testing to minority groups has been controversial but may serve to engage populations that might not have otherwise participated in health-related CGT testing. Second, some companies (eg, InVitae) have developed a hybrid model for CGT testing. In this model, testing is marketed directly to consumers, but health professionals provide the consumer with medical advice regarding selection and interpretation of test results.6 Given the profusion of options for accessing CGT, there is potential for inappropriate testing of consumers who may be less equipped to understand the limitations and potential harms that may arise from engaging in CGT. Clinicians will need to be able to guide patients who have intentionally or less deliberately received, perhaps as a gift, health-related genomic test results.
Cost reductions and increased availability of clinical-quality CGT raises the possibility that CGT may enhance access to genomic services for individuals who have had difficulty obtaining traditional genetic services, including those in underserved and rural populations. However, for some non-European ancestry groups it is likely that CGT may have less useful, and perhaps misleading, information regarding disease risk. This is in part because the genomic data underlying the interpretation of rare and common variant disease risk has been heavily skewed to include individuals of European ancestry. Testing in ancestrally diverse populations may yield ambiguous results, such as reporting increased numbers of variants of unknown significance.7 Gaps in the data for individuals of non-European ancestry can result in both false-positive and false-negative results when CGT companies report risk that is not contextualized by ancestry. This is particularly troubling for African American populations that have disproportionate health burdens from conditions such as breast cancer, type 2 diabetes, and cardiovascular disease. Although not unique to CGT, underattribution or overattribution of risk might have untoward consequences for individuals receiving test results outside of a traditional model of medical care. Although global efforts are underway to close the gap in knowledge about disease variant associations in diverse populations, it seems premature to consider CGT a replacement for medical genetic services delivered in the context of a health care system in which more holistic health risk assessment can be provided.
There is a considerable gap between CGT and integration of the results into their health care for most individuals. This may be particularly true for those engaging in CGT who do not have access to geneticists or genetic counselors, including those in rural populations for whom specialized care is not easily accessed. Ideal models for delivering CGT results that ensure patient understanding and connection to necessary downstream health services are in evolution. Anecdotally, although consumers may express gratitude for having the genetic test available to them, delays in help with rapid support for understanding and acting on CGT results can be emotionally distressing. Many health care professionals and health systems are poorly prepared to help patients with interpretation of genomic testing results and evidence-based approaches to managing newly identified risk. Most electronic health record systems used in the US have no ability to integrate structured genomic data from any source and lack clinical decision support capabilities for genomic test results. It is also not clear whether health care professionals will accept CGT results as valid, or by what metrics validity should be judged. Current regulatory structures under Clinical Laboratory Improvement Amendments and the College of American Pathologists, even when followed by companies that provide CGT, do not ensure the utility of genomic testing. Given the rate of the uptake of CGT, effective approaches for the appropriate integration of valid CGT results into health care systems should developed. Absent this, opportunities for improving health outcomes may be missed.
The current and rapidly evolving landscape of CGT also poses myriad confidentiality, privacy, and data security concerns for consumers and health professionals.8 These concerns go beyond the well-covered potential for long-term care and disability insurance discrimination. For example some CGT companies have developed relationships with academic and commercial third parties for research purposes and profit. As of 2020, no US federal regulations cover data-sharing relationships by commercial entities not be covered by the Health Insurance Portability and Accountability Act. That is, deidentified data can be shared. At least 1 company, LunaDNA, has positioned the consumer as a financial stakeholder in the sharing of DNA sequence and health data, representing a novel approach in which contributing DNA and health data makes participants shareholders in the company. Consumer attitudes regarding data sharing to third parties are poorly understood. However, there have been some examples of companies that targeted unwitting consumers for testing for ill-gained profit that could adversely affect public opinion of all CGT companies.9 Another emerging concern is the use of CGT results by third parties for law enforcement purposes, as evidenced by a number of high-profile criminal cases solved in the US through use of ancestry databases. In 2019, the idea that CGT might affect national security, in part, prompted the US military to warn service members from engaging in CGT.10 Policy makers and regulatory bodies have a considerable task ahead to catch up with the CGT marketplace to ensure transparency and reduce the potential for consumer harm. Health professionals should be cognizant that this area is currently not well regulated. Consumers with concerns about how their data are used should look carefully at the details of user agreements before engaging in CGT.
Since the late 2000s, there has been rapid advancement in the translation of genomic science into health care applications. In parallel, CGT has expanded and evolved in ways that would have been difficult to predict at the time of the completion of the human genome project. Consumers, health professionals, health care system leadership, and policy makers lag behind in understanding the implications of CGT. Additional research is needed to understand how CGT affects individuals and populations, as well as innovative regulatory approaches to maximize potential benefits while safeguarding consumers from potential harms. Nimble and forward-thinking leadership is needed from organizations, including the US Food and Drug Administration, the Centers for Medicare & Medicaid Services, and the Department of Justice, as well as the private sector to ensure that CGT continues to evolve in ways that benefit both individuals and society.
Zdroj: JAMA
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New study shows self-repairing teeth could become the norm in the future
Rarely does the sentence "I have to go to the dentist" evoke much enthusiasm. However, a team of scientists at King's College London (KCL) in the UK has found further proof that our teeth could self-repair. The team has been investigating a method of stimulating natural tooth repair through the activation of cells in the tooth that makes new dentine. Their findings were published in the Journal of Dental Research on Tuesday. A clinical approach Our teeth have three layers, and each of these layers can be affected by decay or trauma. These layers are the outer enamel, dentin — the middle section that works as a protector to the inside of the tooth —, and the inner part of the tooth that's the soft dental pulp. It's vital to keep all three layers healthy. Previous research discovered that a drug called Tideglusib helped to protect that inner layer by stimulating the production of dentin (the middle section), which ultimately led the tooth to repair itself naturally. In an effort to continue testing the drug's viability on patients, over the past five years, the KCL team has been looking into whether enough volume of dentine could be produced to repair cavities in human teeth. They've further looked into the drug's range and safety, and if the mineral composition of the reparative dentin is similar to that which we produce naturally as humans, and whether or not it's strong enough to maintain the strength of the tooth. Professor Paul Sharpe, lead author of this research and Dickinson Professor of Craniofacial Biology at KCL, and his team have discovered that their study does indeed show further positive evidence that the method could be used in clinical practice. The team discovered that the repair area is restricted to pulp cells in the immediate area of repair and that it was significantly different from that of the bone. Moreover, they discovered that the drug can activate repair in an area of dentin damage up to ten times larger, essentially mimicking the size of small cuts in humans. Professor Sharpe stated "In the last few years we showed that we can stimulate natural tooth repair by activating resident tooth stem cells. This approach is simple and cost-effective. The latest results show further evidence of clinical viability and bring us another step closer to natural tooth repair."
Zdroj: New Scientist
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Ancient viruses buried in our DNA may reawaken and cause illness
STRANGE fevers and unusual infections are common among the people
with HIV who come to Avindra Nath’s clinic for treatment. But when one
young man showed up in 2005 struggling to move his arms and legs, Nath
was baffled. Although the man had been diagnosed with HIV a few years
earlier, his new symptoms matched those of amyotrophic lateral sclerosis
(ALS), also known as motor neuron disease. In an attempt to get his HIV
under control, Nath convinced him to start taking antiretroviral drugs.
Much to everyone’s surprise, his ALS symptoms improved too.
ALS is caused by progressive deterioration and death of the nerve
cells that control voluntary movement. What triggers this destruction is
unclear, but recovery is rare. Puzzled, Nath, who ran an immunology
clinic at Johns Hopkins University in Baltimore, began searching the
medical literature. There he found other people with HIV and ALS whose
ALS symptoms improved with antiretrovirals – drugs that stop viruses
replicating. Could this neurological condition be triggered by a dormant
virus hiding in our DNA, brought back to life by HIV?
This question doesn’t only hover over ALS. Increasingly, we are
waking up to the possibility that conditions including multiple
sclerosis (MS), schizophrenia and even type 1 diabetes may in some cases
be triggered by ancient viruses buried in our genomes. Under certain
circumstances, they revive and start producing mutated versions of
themselves, triggering the immune system to attack and destroy
neighbouring tissues.
“It’s a wild new theory of disease,” says Cedric Feschotte, a
molecular biologist at Cornell University in New York. And already it is
pointing the way to new treatments.
Most viruses are only temporary visitors. They make us sick, but soon
we either get better or we die. A century ago, however, biologist
Peyton Rous’s discovery of a cancer-causing virus provided the first
clues that viruses can become resident in our DNA. The discovery began
in 1910, when a woman knocked on his door at the Rockefeller Institute
in New York, clutching her prized Plymouth Rock hen, which had a tumour
called a sarcoma growing on its chest. Curious about its cause, Rous
transplanted a small piece of the tumour into other chickens, and found
that they developed a highly invasive cancer – even when the cancer
cells and any accompanying bacteria were filtered out. The culprit was
Rous sarcoma virus (RSV), a member of a previously unknown group of
viruses called retroviruses, which insert a copy of their genome into
the DNA of the cells they infect. This means they can reproduce without
making infectious particles that could tip off the host’s immune system –
something other viruses can’t do.
The discovery of retroviruses raised an intriguing possibility: if one were to infect a sperm or egg cell (see diagram ),
then viral DNA could be passed from parent to offspring through
successive generations. Although scientists found no evidence that this
happened with RSV, they soon identified several other retroviruses
tucked away in the chicken genome. They named these endogenous retroviruses , because the viruses came from within an animal. By the mid-1980s, we had found them in humans, too.The advent of genome sequencing in the 1990s revealed just how common
these viruses are. Ever since they first evolved about 500 million
years ago, countless retroviruses have buried themselves in the DNA of
their hosts, to the extent that this ancient viral material
now occupies about 8 per cent of the human genome. “You have to
consider these viruses as a very, very old thing that happened to our
ancestors millions of years ago,” says Patrick Küry, a neuroscientist at
Heinrich Heine University Düsseldorf in Germany.
Over the millennia, most of these viral genes have become so riddled
with mutations that they have become the genetic equivalent of fossils:
inert and semi-degraded. There are a couple of exceptions. In humans,
two families of retroviruses have been identified that, under certain
circumstances, can reawaken and start producing small pieces of viral
proteins that can activate the immune system. Not long after this
discovery, signs started to emerge that these enemies within might be
contributing to some relatively common human diseases.
Some of the first evidence came from people with MS, an autoimmune
condition in which the body’s own immune cells start attacking the
protective sheath that wraps around nerve cells, disrupting the messages
they transmit. In 1989, Hervé Perron at the University of Lyon in
France discovered an unknown retrovirus in brain tissue taken from
people with the condition. Further experiments showed that the source of
this virus was the human genome itself. Perron initially named the
virus MS-associated retrovirus, but later sequencing of its genome
revealed that it belonged to a new family of human endogenous
retroviruses (HERVs) that became called HERV-W.
Perron’s work caught the eye of virologist Antonina Dolei at the
University of Sassari in Sardinia, Italy. She began testing people with
no known conditions for traces of Perron’s retrovirus and discovered an
active form of the virus in 12.5 per cent of the general population. She
also tested 39 people with MS and found it in every one of them. Brain
tissue from people who had MS when they died also revealed the presence
of retroviral protein.
“It was just incredible to see,” says Dolei. “If we can be aware of
what’s actually going wrong in neurons, we can potentially change how MS
is treated.”
Dolei couldn’t initially determine whether Perron’s retrovirus was a
cause of MS or a result of the disease process. But as she followed
patients over time, she found that the amount of virus in the blood
predicted the disease’s progression and severity. What’s more, the
response to MS drugs and remission of symptoms correlated with reduced
levels of retroviral proteins in the blood and the cerebrospinal fluid
surrounding the brain and spinal cord. This suggested that HERV-W might
somehow be playing a role.
Frankenstein’s molecules
By the time that young man walked into Nath’s HIV clinic in 2005,
evidence was also mounting for the role of HERV-W in schizophrenia. Håkan Karlsson ,
now at the Karolinska Institute in Stockholm, had identified traces of a
retroviral protein called pol in the cerebrospinal fluid of about a
third of people he examined who had been recently diagnosed with
schizophrenia. Again, the source seemed to be the individuals’ own DNA.
As a retrovirologist, Nath had heard of Karlsson’s work, and,
suspecting that his patient’s symptoms may have a similar cause, he
approached Jeffrey Rothstein, an ALS expert who worked in a neighbouring
lab. They started to examine brain tissue from 28 people who had had
ALS when alive, and they detected RNA from a retrovirus called HERV-K in
every single one. It was compelling evidence for the role of
retroviruses in ALS, but still didn’t prove causation. Nath couldn’t
rule out that dying nerve cells may have activated the virus.
It was similarly unclear how such activation might be contributing to
nerve cell damage in schizophrenia or MS. The baton was picked up by
Küry, who had been studying the cascade of events leading to the
degeneration of nerve cells in MS. Küry realised that the evidence for
HERV-W contributing to MS was circumstantial at best. “The question in
MS is always what comes first,” says Küry. “There has to be some trigger
that sends the body towards an autoimmune response, but no one
understands how this happens.”
Küry realised that he would have to look at how HERV-W interacts with
neighbouring brain cells. Using brain tissue from deceased MS patients,
Küry and his colleagues showed that a HERV-W protein called ENV activates brain-based immune cells called microglia ,
which not only directly damage neurons, but also interfere with their
repair. “Now that we’ve identified a protein, we can start to think
about how to neutralise it with an antibody,” says Küry, who published
the results last year.
Although in some people with MS the body might be synthesising
proteins from HERV-W and other endogenous retroviruses, Karlsson
stresses that individuals aren’t producing a fully functional virus that
can infect other people. Rather, it is something about the proteins
produced and the body’s response to them that is the problem. In small
studies of people with schizophrenia, scientists found pHERV-W
slightly elevated levels of an inflammatory molecule called C-Reactive
protein. This could indicate that, in some people, the immune system is
responding to a virus. Karlsson still doesn’t know whether this is the
result of endogenous retroviruses or how it might contribute to the
condition.
Despite mounting evidence for the role of retroviruses in common
illnesses, questions remain. For one thing, it is still unclear what
proportion of MS, ALS and schizophrenia cases are related to the
reactivation of these ancient viral stowaways. Their existence also
doesn’t rule out other potential causes.
Another question is how we can carry copies of the viruses without
feeling major ill effects. If HERV-W is thought to be buried in all our
genomes, why does it only wake up and start causing problems in some
people?
Our cells work hard to prevent these viral genes from being
translated into proteins. The cell twists DNA into a complicated 3D
snarl, and its protein-making machinery can only access genes on the
surface of this tangle. As long as the hidden viruses remain buried in
the middle, they are effectively silenced. And if that isn’t enough, the
body has proteins whose main job is to suppress the production of any
endogenous retroviral proteins. The slow accumulation of genetic
mutations over time adds an additional layer of protection as they often
render the viral proteins non-functional.
However, these fail-safes aren’t perfect, and studies suggest that
our cells may be less able to keep these elements suppressed during
times of stress. “When a cell is in crisis, it can make mistakes,” says Molly Gale Hammell , a geneticist at Cold Spring Harbor Laboratory in New York. One such source of stress is infection with another virus.
Dolei notes that a disproportionate number of her MS patients report having experienced glandular fever (infectious mononucleosis)
– caused by infection with the Epstein-Barr virus – as teenagers or
young adults. Possibly, the infection triggers changes in DNA folding
that leave some previously buried viruses exposed, prompting them to
stagger to life like molecular versions of Frankenstein’s monster. In
the case of people with HIV, their weakened immune systems may be less
able to spot and destroy cells containing reactivated viruses.
Internal warfare
All humans have these fossil viruses in our DNA, and we all age and
experience multiple infections, yet most of us will never develop MS,
ALS or schizophrenia. Küry hypothesises that a combination of virus
reactivation and a genetic predisposition is required to lead to
illness. This may be bad news for individuals, but the reactivation of
these clandestine viruses may also create the perfect Achilles’ heel in
some of the conditions they cause.
As an HIV doctor in the late 1980s and early 1990s, Nath had a front-row seat to the lifesaving power of antiretroviral drugs .
He prescribed them to all his patients – including the young man with
ALS. That the drugs decreased the amount of HIV in the man’s blood and
boosted his T-cell counts was no surprise to Nath. But the rapid
improvement of ALS-like symptoms in people with HIV hinted that these
drugs might be effective against other retroviruses: the resurrected
fossils in our genomes. He is now recruiting people for a small pilot
study to test whether giving a cocktail of three antiretroviral drugs is
beneficial to people with ALS who don’t have HIV and who have high
levels of HERV-K activity. A recent study suggests that this group may
comprise a fifth of people with ALS.
Meanwhile, Hammell has used machine learning to analyse gene activity
in brain cells from recently deceased ALS patients. Her analysis,
published in October 2019 in Cell Reports , identified three subtypes of ALS, one of which was dominated by hidden viruses in the genome.
Possibly the biggest advance has come from a Swiss pharmaceutical
company called GeNeuro, which Perron established in 2006 to develop new
treatments for MS based on targeting retroviral proteins. GeNeuro is
testing a drug called temelimab, which binds to the ENV protein from
HERV-W and triggers its destruction. The results of a trial in 270
people with MS, presented at a scientific conference last September,
suggests that the drug slows the shrinkage of brain tissue by 40 per
cent. This is one of the most destructive consequences of the disease,
and may be what leads to irreversible neurological and cognitive
impairments. With existing MS therapies doing little to slow disease,
Dolei says temelimab represents a huge advance.
The company has also begun testing temelimab in people with type 1
diabetes, another autoimmune condition, caused by the destruction of
insulin-producing beta cells in the pancreas. The move comes after a
2017 study identified HERV-W activity in the pancreatic cells of about
half of a group of people with type 1 diabetes. And the firm is working
on antibodies to treat ALS and certain types of psychosis related to
schizophrenia that have also been associated with retrovirus activation.
It is early days, but the development of such drugs could transform
the war that has been raging between us and viruses since our earliest
beginnings. “Our cells have been fighting these things over evolutionary
time scales – battles they have mostly won, in the sense that we are
still here,” says Hammell. With the drugs on our side we may win another
important victory against the invisible enemies hidden in our genomes.
Zdroj: New Scientist
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CRISPR-edited chickens made resistant to a common virus
CRISPR genome editing
has been used to make chickens resistant to a common virus. The
approach could boost egg and meat production worldwide while improving
welfare.
The altered chickens
showed no signs of disease even when exposed to high doses of the avian
leukosis virus (ALV). The virus is a problem for poultry farmers around
the world, says Jiri Hejnar at the Czech Academy of Sciences.
Infected birds become ill, emaciated and depressed, and often develop
tumours. The virus gets into cells by binding to a protein called
chicken NHE-1 (chNHE-1). Hejnar’s team has previously shown that
deleting three DNA letters from the chNHE-1 gene that makes this protein prevents ALV from infecting chicken cells.
The challenge was to make this change in entire animals rather than
just in a few cells. No strains of chickens naturally have this
mutation, so it can’t be done by breeding alone. But genetically
modifying chickens is more difficult than modifying other animals such as pigs .
The conventional method is to extract so-called primordial germ
cells, alter them outside the body and then add the modified cells to
embryos inside freshly laid eggs. This approach was used to create CRISPR chickens in 2016 , but the success rate is extremely low.
In 2017, Hejnar developed a better method: using altered germ cells
to restore semen production in sterilised cockerels. His team then went
on to create a cockerel with sperm that have the precise deletion in the
chNHE-1 gene.
By crossing its offspring, they have produced a flock of white
leghorn chickens that have this deletion in both copies of the gene.
Zdroj: New Scientist
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Ancestral home of all human beings discovered by scientists
Scientists have pinpointed a fertile river valley in northern Botswana as the ancestral home of all human beings .
The earliest anatomically modern humans (Homo sapiens ) arose 200,000 years ago in a vast wetland south of the Zambezi river which was the cradle of all mankind, a new study has revealed.
This lush region – which also covered parts of Namibia and Zimbabwe – was home to an enormous lake which sustained our ancestors for 70,000 years, according to the paper published in the journal Nature .
Between 110,000 and 130,000 years ago, the climate started to change and fertile corridors opened up out of this valley. For the first time, the population began to disperse – paving the way for modern humans to migrate out of Africa , and ultimately, across the world.
Lead researcher Professor Vanessa Hayes, a geneticist at the Garvan Institute of Medical Research in Australia, said: “It has been clear for some time that anatomically modern humans appeared in Africa roughly 200,000 years ago.
“What has been long debated is the exact location of this emergence and subsequent dispersal of our earliest ancestors.”
Professor Hayes and her colleagues collected blood samples from study participants in Namibia and South Africa and looked at their mitochondrial DNA (mtDNA).
As mtDNA is passed almost exclusively from mother to child through the egg cell and its sequence stays the same over generations, making it a useful tool for looking at maternal ancestry.
The team focused their research on the L0 lineage – modern human’s earliest known population – and compared the complete DNA code (mitogenome) from different individuals. They also looked at other sub-lineages across various locations in Africa to see how closely they were related.
The researchers then combined genetics with geology and climatic physics, to paint a picture of what the world looked like 200,000 years ago.
Geological evidence suggests the homeland region once housed Africa’s largest ever lake system, known as Lake Makgadikgadi which was double the size of modern Lake Victoria.
And climate computer model simulations indicate that “the slow wobble of Earth’s axis” brought “periodic shifts in rainfall” across the region.
Professor Axel Timmermann, a climate scientist at Pusan National University in South Korea, said: “These shifts in climate would have opened green, vegetated corridors, first 130,000 years ago to the northeast, and then around 110,000 years ago to the southwest, allowing our earliest ancestors to migrate away from the homeland for the first time.”
Professor Hayes said: “We observed significant genetic divergence in the modern humans’ earliest maternal sub-lineages that indicates our ancestors migrated out of the homeland between 130,000 and 110,000 years ago.
“The first migrants ventured northeast, followed by a second wave of migrants who travelled southwest. A third population remained in the homeland until today.”
Researchers believe that the humans who migrated southwest flourished and experienced steady population growth. They say this could be due to an adaptation to marine foraging.
“These first migrants left behind a homeland population,” said Professor Hayes.
“Eventually adapting to the drying lands, maternal descendants of the homeland population can be found in the greater Kalahari region today.”
Zdroj: The Independent
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Two Sisters Bought DNA Kits. The Results Blew Apart Their Family
Sonny and Brina Hurwitz raised a family in Boston. They both died with secrets.
In
2016, their oldest daughter, Julie Lawson, took a home DNA test. Later,
she persuaded her sister, Fredda Hurwitz, to take one too.
In
May, the sisters sat down at the dinner table in Ms. Hurwitz’s Falls
Church, Va., home to share their results. A man’s name popped up as a
close genetic match for Ms. Hurwitz. Neither had ever heard of him.
Ms.
Lawson searched for the man on Facebook. When she saw his photos, she
knew. He looked like their late father. Based on his age and the close
physical resemblance, Ms. Lawson immediately told her sister, “He’s got
to be our brother.” This was their father’s secret. He had a child they
never knew about.
Then came a second shock.
Ms. Lawson’s test showed she didn’t appear to have any genetic
connection to this new man. This was their mother’s secret: Ms. Lawson
was the product of a brief extramarital affair. The man who raised her
wasn’t her biological father.
The
revelations ricocheted through the family. They created new bonds with
people who were once strangers. They caused tension with family they had
known all their lives. And they sparked a fight between the sisters
about the bonds of loyalty—and how much their parents should have told
them.
Ms. Lawson, 65 years old, said she is
still grappling with “the pain of knowing my life was a lie and having
all these questions that can’t be fully answered because both my parents
are gone.”
The hardest part, she said, came the moment she and Ms. Hurwitz, 52, realized they were half, not full, sisters.
“We held each other,” Ms. Lawson said, “and we sobbed.”
At a time of ubiquitous direct-to-consumer genetic testing ,
family confidences are almost impossible to keep. Companies sell their
products for under $100, pitched through heartwarming ads. Millions of DNA kits have been sold in recent years that have handed over information both useful and shocking .
Sales
of DNA tests are soaring as people seek to learn more about their
roots. Ancestry, whose tests the sisters used, reported sales of 14
million DNA kits world-wide as of November, up from 3 million in 2016. A
paper published in Genome Biology, a scientific journal, last year
estimated more than 100 million people will have their DNA tested by
2021.
Ancestry provides customers who choose
to do so with a way to connect online with others who are DNA matches.
The company said it has “a small, dedicated group of highly experienced
representatives who speak to customers with more sensitive queries.”
Genetic
counselor Brianne Kirkpatrick, founder of Watershed DNA, which provides
consultations to people with DNA questions, advises clients to consider
how and whether to share certain information. “If you have a secret or
think something might be uncovered through DNA testing, start preparing
what you want to share ahead of time when you can be in control,” she
said.
Ms. Kirkpatrick sometimes suggests
clients write letters, explaining details behind their children’s
genetic origins, which they can give if the secret is revealed. “I have
become of the mind-set it is not a matter of if the secrets will come
out,” she said. “It is a matter of when the secrets will come out.”
Given
the rapid growth of consumer genetic testing, people can often be
identified even if they don’t take a test themselves. Some people who
take tests share family trees online. Amateur genealogists and
researchers can identify additional connections through obituaries,
wedding announcements, and other public information.
In
a paper published in October in the journal Science, researchers
estimated over 60% of individuals of European descent in the U.S. now
have a third cousin or closer relative in a database. “DNA tests can
reveal that there is something odd going on,” said Yaniv Erlich, one of
the authors and chief science officer of DNA-testing company MyHeritage.
“But they don’t tell you the story of what happened.”
In
Falls Church, after the test results came back, the sisters sat
together and kept staring at pictures of a stranger who looked like
their Dad.
Ms. Hurwitz, exhausted and
emotional, told her sister she was going to sleep. Ms. Lawson didn’t
want to wait another moment. She messaged the man, Dana Dolvin, telling
him an Ancestry test showed he was a relative, and suggested they talk.
He responded right away. It turned out he lived near Falls Church.
He agreed to meet at Ms. Hurwitz’s home the next day. He assumed they might be cousins.
When
they met, the sisters showed him picture after picture of their late
father. The resemblance was uncanny, they all agreed; the eyes, the
ears, the height, even down to the glasses and love of wearing hats.
Mr.
Dolvin, 62, never met the man listed on his birth certificate as his
father, who was his late mother’s husband. The couple, both
African-American, divorced after his birth. Mr. Dolvin, who has seen
pictures, said, “I didn’t look like him.”
When
Mr. Dolvin received his own test results, they indicated his DNA was
47% European Jewish. “I kind of figured my Dad was a fair-skinned
person,” he said.
He wasn’t sure he would
ever identify his father, or even if the man was still alive. Relatives
of the man might not want to share private information with a stranger
or might not approve of the fact his parents weren’t the same race.
“People don’t want to rock the boat,” he said. “They also may have different feelings toward people of color.”
The
sisters say they knew their parents had marital difficulties over the
years so it wasn’t a shock to learn their father had an affair. Their
parents had a wide circle of friends that included people of different
religious and racial backgrounds so they say they weren’t surprised
their father had an interracial relationship.
“My surprise was that a child existed,” said Ms. Hurwitz. “And he looked so much like Dad.”
Mr.
Dolvin wasn’t certain the women’s assumptions about their father were
correct. It was hard to believe, he said, “that I finally got an answer
to the question haunting me for such a long time.” He went home and
wondered, “Are they really my siblings?”
Siblings
share around half their DNA. Half-siblings share a quarter, and first
cousins, on average, share 12.5%. Mr. Dolvin checked his report and
compared the shared DNA for him and Ms. Hurwitz: It indicated they were
half-siblings.
That night, excited by Mr.
Dolvin’s visit, Ms. Lawson couldn’t sleep. That is also when she began
to wonder why his name hadn’t come up on her results. Why did he have a
genetic relationship only with her sister?
Ms. Lawson asked for help answering that question from Larry Alssid ,
64, a Long Island, N.Y., psychologist, who had contacted her after he
took an Ancestry test a few years ago, showing they were related. They
could never figure out their connection but had kept in touch.
After
hearing her news, Dr. Alssid suspected Ms. Lawson might have a
different biological parent than her sister. He didn’t want to be the
one to tell her the potentially shattering information. “I slept on it,”
he said.
He told her to check the amount
of DNA she and her sister shared in common. Soon she understood: She and
her sister didn’t have the same biological parents—or father, to be
precise.
“I did regret I told her because she was in shock,” Dr. Alssid said. “We still didn’t know who her father was.”
Later, Dr. Alssid consulted a family tree and gave her names of four brothers—distant relatives he had never met —who he thought could be a match.
Based on their ages, the two youngest, Jack and Ira Greenberg, he said, were the likeliest candidates.
“Jack
or Ira? My mother never mentioned those names,” Ms. Lawson recalled
saying. She doubted she would find the answers she wanted.
Dr.
Alssid told her that a nephew of Jack and Ira might know more. The
nephew, whom she emailed, told her all the brothers went by nicknames.
The youngest, Ira, was known as Hy.
“That is when I knew,” said Ms. Lawson. “My mother always told me that her first love was a boy named Hy.”
Hy
Greenberg was the only brother still alive. An 89-year-old retired
traveling salesman, he never married and was living in Florida. His
nephew called him about Ms. Lawson’s quest. He agreed to a phone
conversation.
She started slowly, telling him she was doing a family tree. Did he know a woman named Brina?
He immediately recognized the name. “Yes,” he said. “I dated her, my best friend introduced us.”
Later
in the conversation, she asked the key question. “I have to get
personal,” she said. “Would your relationship have included sex?”
Mr. Greenberg said yes.
“You are my father,” Ms. Lawson told him. “I am your daughter.”
“You’ve got to be kidding,” Mr. Greenberg said.
Mr.
Greenberg had never done a DNA test. He wasn’t interested. And he
struggled to understand how Ms. Lawson could use the DNA test results of
other relatives of his to identify him as her father. Later, at Ms.
Lawson’s request, he sent in his own kit. The results indicated they
were parent and child.
During their first
call, he shared details of his early dates with her mother after he got
out of the Navy. She wanted to get serious, he said, but he told her he
wasn’t interested in marrying. They briefly rekindled the connection
years later, after her mother was married. Then they parted ways again.
He
never imagined himself being a father, but found they shared a similar
sense of humor and a love of storytelling; the conversation lasted
hours. She suggested they meet. Mr. Greenberg hesitated, then said, “You
want to come, come.”
In June, Ms. Lawson
caught a flight to Florida and knocked on the door of her biological
father. It was Father’s Day weekend. He called her darling and gave her a
hug.
“Welcome home,” he said.
The
visit led Ms. Lawson and her sister to have an intense fight. Ms.
Lawson posted a picture of herself and Mr. Greenberg on Facebook, and
added she was spending her first Father’s Day with her father.
“I
was furious,” said her sister, Ms. Hurwitz. “I was in tears. I told her
Dad is still Dad, and you have just negated his entire existence and
everything he ever did for you with that one post.”
Ms.
Lawson said she never meant any disrespect to their late father. “I
felt misunderstood,” she said. “My brain was so caught up in what is
going on.”
She says she feels a powerful
emotional connection to her biological father. The next time she went to
see him, she took her sister along.
Meeting
him was difficult for Ms. Hurwitz. She kept wondering if he was the man
whom her mother preferred over her father. “I didn’t know what to say
or how to act.”
Getting to know her new half
brother has been easier for her. And it has answered questions for him,
too. “I finally got the answer that wasn’t supplied to me by people who
loved me and who I loved,” he said.
Growing
up, his cousins teased him about the light color of his skin, calling
him “white boy,” he said. An only child, he frequently asked his mother
about his origins. “Don’t worry about it,” he says she told him. He
stopped asking when he was a teenager; his mother died decades ago.
“I
was still curious, but no one would tell me,” he said. “Emotionally,
you wish it could have been another way, but unfortunately, it isn’t.”
In
the months since they met, the sisters and Mr. Dolvin, and members of
their families, have met for dinners and outings. During a visit in
Boston, Ms. Lawson took Mr. Dolvin around the neighborhood where she
grew up, pointing out family landmarks. He refers to both women as his
sisters, even though he shares a biological father with only one.
So
far, the sisters’ other two siblings, both men, haven’t expressed
interest in meeting Mr. Dolvin. Phil Hurwitz, 63, who was born six
months before Mr. Dolvin, said he remains unsure “how I want to move
forward.”
Ms. Lawson got upset with her brother Phil for not reaching out to Mr. Dolvin. She asked him when he might feel ready.
“I told her I am not putting a time frame on it,” he said. Their other brother didn’t respond to requests for comment.
Mr.
Dolvin said he doesn’t think it is his place to contact the two
brothers. He said he would let them decide “if they want to welcome me
or say ‘hi’…” His voice trailed off for a moment.
“Maybe they don’t feel comfortable with it yet. It’s a lot to take in.”
Ms.
Hurwitz said the news that both parents had children from extramarital
affairs forced a kind of reckoning she wasn’t sure her brothers were
ready to make.
“They have to reconsider
completely who their parents were, the lessons they taught us, what they
stood for,” she said. “Everyone deals with the emotions differently.”
She
looked at her sister, who cried quietly at the table. “It is not up to
me to judge the decisions Mom and Dad made,” Ms. Hurwitz said. “It was
another world and another time.”
Ms. Lawson said, “I have a hard time when people say it’s the past, move on.”
Mr. Dolvin put his arm around her, comforting her. “I like that we are all together. I’m here. I’m sitting with you.”
There
are many unresolved and hard-to-answer questions, such as whether their
father was ever told Mr. Dolvin was his son. They don’t think their
father knew. “I believe if he knew about Dana, he would have tried to
reach out,” Ms. Hurwitz said.
Her father
owned a popular kosher deli in a Boston neighborhood. Mr. Dolvin’s
mother worked as a cosmetologist in a nearby predominantly
African-American neighborhood. Both loved jazz; the siblings speculate
the two might have met at one of Boston’s jazz clubs.
The
sisters believe their mother knew Ms. Lawson was the product of her own
affair. Ms. Lawson and her mother had a difficult relationship, and
both sisters think the revelation explains why.
“Julie
was a reminder of what Mom did,” Ms. Hurwitz says. “She had to deal
with the consequences every day. How did she keep the secret from Dad?”
Both sisters acknowledge they also can’t be sure what either parent shared with the other.
When
Ms. Lawson was 29 and Ms. Hurwitz was 16, their parents divorced—and
then got remarried nine years later. They stayed together until he died
in 2006. His wife died in 2016.
Ms. Lawson
says she told her mother she got DNA test results back, but her mother
wasn’t interested in talking about them. She died before the second
sister took the test whose results revealed so much.
The sisters always return to how much their parents should have told them. Even now, hurt and tensions sometimes flare.
“I
understand why you wouldn’t tell,” said Ms. Hurwitz. “The implications
of revealing the secret have a domino effect on everyone else in the
family.”
Her sister vehemently disagrees.
“Every man has a right to know he has offspring,” said Ms. Lawson.
“Every child has the right to know her origins. We missed 65 years
together.”
Ms. Lawson wears a birthday
present she received from Mr. Greenberg, a necklace of two open hearts
connected by her birthstone. She is helping plan a party for his 90th
birthday in March.
Since the sisters learned
the truth, they said they are learning to live with the uncertainties.
“I have my anger, my compassion, and my understanding, and I can
separate all those emotions,” Ms. Lawson said.
Ms. Hurwitz leaned in closer to her sister. “Every family has secrets,” she said.
Zdroj: web
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Scientists develop 10-minute universal cancer test
Scientists have developed a universal cancer test that can detect traces of the disease in a patient’s bloodstream.
The cheap and simple test uses a colour-changing fluid to reveal the presence of malignant cells anywhere in the body and provides results in less than 10 minutes.
While the test is still in development, it draws on a radical new approach to cancer detection that could make routine screening for the disease a simple procedure for doctors.
“A major advantage of this technique is that it is very cheap and extremely simple to do, so it could be adopted in the clinic quite easily,” said Laura Carrascosa, a researcher at the University of Queensland.
The test has a sensitivity of about 90%, meaning it would detect about 90 in 100 cases of cancer. It would serve as an initial check for cancer, with doctors following up positive results with more focused investigations.
“Our technique could be a screening tool to inform clinicians that a patient may have a cancer, but they would require subsequent tests with other techniques to identify the cancer type and stage,” Carrascosa said.
The test was made possible by the Queensland team’s discovery that cancer DNA and normal DNA stick to metal surfaces in markedly different ways. This allowed them to develop a test that distinguishes between healthy cells and cancerous ones, even from the tiny traces of DNA that find their way into the bloodstream.
Healthy cells ensure they function properly by patterning their DNA with molecules called methyl groups. These work like volume controls, silencing genes that are not needed and turning up others that are. In cancer cells, this patterning is hijacked so that only genes that help the cancer grow are switched on. While the DNA inside normal cells has methyl groups dotted all over it, the DNA inside cancer cells is largely bare, with methyl groups found only in small clusters at specific locations.
Writing in the journal Nature Communications, the Queensland team described a series of tests that confirmed the telltale pattern of methyl groups in breast, prostate and colorectal cancer as well as lymphoma. They then showed that the patterns had a dramatic impact on the DNA’s chemistry, making normal and cancer DNA behave very differently in water. “This is a huge discovery that no one has grasped before,” said Carrascosa.
After a series of experiments, the scientists hit on the new test for cancer. The suspect DNA is added to water containing tiny gold nanoparticles. Though made of gold, the particles turn the water pink. If DNA from cancer cells is then added, it sticks to the nanoparticles in such a way that the water retains its original colour. But if DNA from healthy cells is added, the DNA binds to the particles differently, and turns the water blue. “The test is sensitive enough to detect very low levels of cancer DNA in the sample,” Carrascosa said.
Led by Matt Trau, a professor of chemistry at the University of Queensland, the researchers have run the test on 200 human cancer samples and healthy DNA. “We certainly don’t know yet whether it’s the holy grail for all cancer diagnostics, but it looks really interesting as an incredibly simple universal marker for cancer, and as an accessible and inexpensive technology that doesn’t require complicated lab-based equipment like DNA sequencing,” Trau said.
The scientists are now working towards clinical trials with patients that have a broader range of cancer types than they have tested so far.
To test for cancer today, doctors must collect a tissue biopsy from a patient’s suspected tumour. The procedure is invasive and relies on the patient noticing a lump, or reporting symptoms that their GP recognises as a potential sign of cancer. A less invasive test that has the potential to spot cancer earlier could transform how patients are screened for the disease.
The DNA in cancer cells can be riddled with mutations that drive the growth of a specific tumour, but these mutations tend to differ depending on the type of cancer. A universal cancer test would not be precise enough to pinpoint the location or size of a tumour, but would give doctors a swift answer to the question: does this patient have cancer?
Tests in the lab showed that the scientists could distinguish normal DNA from cancer DNA by looking for a colour change in the gold particle solution that was visible to the naked eye within a few minutes.
“This test could be done in combination with other simple tests, and become a powerful diagnostic tool that could not just say that you have cancer, but also the type and stage,” said Carrascosa.
Ged Brady, of the Cancer Research UK Manchester Institute, said: “This approach represents an exciting step forward in detecting tumour DNA in blood samples and opens up the possibility of a generalised blood-based test to detect cancer. Further clinical studies are required to evaluate the full clinic potential of the method.”
Zdroj: web
zpět
HIPAA and Protecting Health Information in the 21st Century
I n March 2018, the Trump administration announced a new
initiative, MyHealthEData, to give patients greater access to their
electronic health record and insurance claims information.1
The Centers for Medicare & Medicaid Services will connect Medicare
beneficiaries with their claims data and increase pressure on health
plans and health care organizations to use systems that allow patients
to access and send their health information where they like.
MyHealthEData
is part of a broader movement to make greater use of patient data to
improve care and health. The movement seeks to make information
available wherever patients receive care and allow patients to share
information with apps and other online services that may help them
manage their health. At the population level, this approach may help
identify optimal treatments and ways of delivering them and also connect
patients with health services and products that may benefit them.
Analysis of deidentified patient information has long been the
foundation of evidence-based care improvement, but the 21st century has
brought new opportunities. With developments in information technology
and computational science that support the analysis of massive data
sets, the “big data” era has come to health services research.
For
all its promise, the big data era carries with it substantial concerns
and potential threats. Part of what enables individuals to live full
lives is the knowledge that certain personal information is not on view
unless that person decides to share it, but that supposition is becoming
illusory. The increasing availability and exchange of health-related
information will support advances in health care and public health but
will also facilitate invasive marketing and discriminatory practices
that evade current antidiscrimination laws.2
As the recent scandal involving Facebook and Cambridge Analytica shows,
a further risk is that private information may be used in ways that
have not been authorized and may be considered objectionable.
Reinforcing such concerns is the stunning report that Facebook has been
approaching health care organizations to try to obtain deidentified
patient data to link those data to individual Facebook users using
“hashing” techniques.3
Given
these concerns, it is timely to reexamine the adequacy of the Health
Insurance Portability and Accountability Act (HIPAA), the nation’s most
important legal safeguard against unauthorized disclosure and use of
health information. Is HIPAA up to the task of protecting health
information in the 21st century?
HIPAA Framework for Information Disclosure
HIPAA was considered ungainly when it first became law, a
complex amalgamation of privacy and security rules with a cumbersome
framework governing disclosures of protected health information. HIPAA
has been derided for being too narrow—it applies only to a limited set
of “covered entities,” including clinicians, health care facilities,
pharmacies, health plans, and health care clearinghouses—and too onerous
in its requirements for patient authorization for release of protected
health information. Over time, however, HIPAA has proved surprisingly
functional. Particularly after being amended in the 2009 HITECH (ie, the
Health Information Technology for Economic and Clinical Health) Act to
address challenges arising from electronic health records, HIPAA has
accomplished its primary objective: making patients feel safe giving
their physicians and other treating clinicians sensitive information
while permitting reasonable information flows for treatment, operations,
research, and public health purposes.
HIPAA’s Privacy
Rule generally requires written patient authorization for disclosure of
identifiable health information by covered entities unless a specific
exception applies, such as treatment or operations. Researchers may
obtain protected health information (PHI) without patient authorization
if a privacy board or institutional review board (IRB) certifies that
obtaining authorization is impracticable and the research poses minimal
risk. The investigators can obtain a limited data set that excludes
direct identifiers (eg, names, medical record numbers) without patient
authorization if they agree to certain security and confidentiality
measures. Importantly, data sets from which a broader set of 18 types of
potentially identifying information (eg, county of residence, dates of
care) has been removed may be shared freely for research or commercial
purposes.
This has been a serviceable framework for
regulating the flow of PHI for research, but the big data era raises new
challenges. HIPAA contemplated that most research would be conducted by
universities and health systems, but today much of the demand for
information emanates from private companies at which IRBs and privacy
boards may be weaker or nonexistent. Additionally, removing identifiers
to produce a limited or deidentified data set reduces the value of the
data for many analyses. Moreover, the increasing availability of
information generated outside health care settings, coupled with
advances in computing, undermines the historical assumption that data
can be forever deidentified.4
Startling demonstrations of the power of data triangulation to
reidentify individuals have offered a glimpse of a very different
future, one in which preserving privacy and the big data enterprise are
on a collision course.4
It
will be difficult to reconcile the potential of big data with the need
to protect individual privacy. One reform approach would be data
minimization (eg, limiting the upstream collection of PHI or imposing
time limits on data retention),5
but this approach would sacrifice too much that benefits clinical
practice. Another solution involves revisiting the list of identifiers
to remove from a data set. There is no doubt that regulations should
reflect up-to-date best practices in deidentification.2 ,4
However, it is questionable whether deidentification methods can
outpace advances in reidentification techniques given the proliferation
of data in settings not governed by HIPAA and the pace of computational
innovation. Therefore, expanding the penalties and civil remedies
available for data breaches and misuse, including reidentification
attempts, seems desirable.
Limited Reach of HIPAA
HIPAA “attaches (and limits) data protection to traditional health care relationships and environments.”6
The reality of 21st-century United States is that HIPAA-covered data
form a small and diminishing share of the health information stored and
traded in cyberspace. Such information can come from well-known sources,
such as apps, social media, and life insurers, but some information
derives from less obvious places, such as credit card companies,
supermarkets, and search engines. For example, non–health information
that supports inferences about health is available from purchases that
users make on Amazon; user-generated content that conveys information
about health appears in Facebook posts; and health information is
generated by entities not covered by HIPAA when over-the-counter
products are purchased in drugstores. Because HIPAA’s protection applies
only to certain entities, rather than types of information, a world of
sensitive information lies beyond its grasp.2
HIPAA
does not cover health or health care data generated by noncovered
entities or patient-generated information about health (eg, social media
posts). It does not touch the huge volume of data that is not directly
about health but permits inferences about health. For example,
information about a person’s physical activity, income, race/ethnicity,
and neighborhood can help predict risk of cardiovascular disease. The
amount of such data collected and traded online is increasing
exponentially and eventually may support more accurate predictions about
health than a person’s medical records.2
Statutes
other than HIPAA protect some of these non–health data, including the
Fair Credit Reporting Act, the Family Educational Rights and Privacy Act
of 1974, and the Americans with Disabilities Act of 1990.7
However, these statutes do not target health data specifically; while
their rules might be sensible for some purposes, they are not designed
with health in mind. For instance, the Family Educational Rights and
Privacy Act of 1974 has no public health exception to the obligation of
nondisclosure. 7
To
ensure adequate protection of the full ecosystem of health-related
information, 1 solution would be to expand HIPAA’s scope. However, the
Privacy Rules’ design (ie, the reliance on IRBs and privacy boards, the
borders through which data may not travel) is not a natural fit with the
variety of nonclinical settings in which health data are collected and
exchanged.8
The
better course is adopting a separate regime for data that are relevant
to health but not covered by HIPAA. One option that has been proposed is
to enact a general rule protecting health data that specifies further,
custodian-specific rules; another is to follow the European Union’s new
General Data Protection Regulation in setting out a single regime
applicable to custodians of all personal data and some specific rules
for health data. The latter has the appeal of reaching into non–health
data that support inferences about health. Any new regulatory steps
should be guided by 3 goals: avoid undue burdens on health research and
public health activities, give individuals agency over how their
personal information is used to the greatest extent commensurable with
the first goal, and hold data users accountable for departures from
authorized uses of data.
Rethinking regulation should
also be part of a broader public process in which individuals in the
United States grapple with the fact that today, nearly everything done
online involves trading personal information for things of value. When
such trades are made explicit, as when drugstores offered customers $50
to grant expanded rights to use their health data, they tend to draw
scorn.9
However, those are just amplifications of everyday practices in which
consumers receive products and services for free or at low cost because
the sharing of personal information allows companies to sell targeted
advertising, “deidentified” data, or both.
Improved public understanding of these practices may lead
to the conclusion that such deals are in the interest of consumers and
only abusive practices need be regulated. Or it may create pressure for
better corporate privacy practices. Some consumers may take steps to
protect the information they care most about, such as purchasing a
pregnancy test with cash. Shaping health information privacy protections
in the 21st century requires savvy lawmaking as well as informed
digital citizens.
Zdroj: web
zpět
The murder that has obsessed Italy
On 26 November 2010, Yara Gambirasio, 13, went missing. Three months later her body was discovered in scrubland nearby. So began one of the most complex murder investigations in Italian history, which will reach its climax later this year Yara Gambirasio should only have been gone a short while. On Friday 26 November 2010, at 5.15pm, she left home to go to the gym, just a few hundred metres from her home. Yara, who was 13 and wore train-track braces, was preparing for her rhythmic gymnastics display the following Sunday. All she needed to do was drop off a stereo with her instructor. She said goodbye to her family, who knew where she was going, and left the house. By 7pm, Yara had still not come home and her parents were becoming increasingly anxious. The town where they lived, Brembate di Sopra, was a sedate place, on the so-called “Bergamask island” between the rivers Brembo and Adda. An hour north of Milan, and just south of the Bergamo Alps, it has a population of 8,000. From its quiet streets, lined with poplars and cypresses, you can see the wooded mountains in the distance, the peaks turning blue-grey. At 7.11pm, Yara’s mother phoned her daughter, but the call went straight to voicemail. Twenty minutes later, Yara’s father called the police. The call was put through to the public prosecutor’s office, in the centre of the provincial capital Bergamo, a city 11km east of Brembate di Sopra. The magistrate on duty was Letizia Ruggeri, 45, a tough former policewoman who had earned her stripes fighting Cosa Nostra in Sicily. She had been a magistrate for almost 15 years, and knew what needed to be done. Within minutes she had dispatched both state police officers and carabinieri, military police, to Brembate di Sopra. Yara’s gym instructor confirmed that she had seen the teenager earlier that day and that she had done some light training before heading off. The police quickly established that the last known contact with Yara was a text message she had sent to a friend, Martina, at 6.44pm, agreeing to meet at 8am the following Sunday. That was the last anyone heard from her. The gym was part of a large sports complex, a garish building with many entrances and exits. Besides the large sports hall there was a running track, a swimming pool, and various courts. A few people said they’d seen two men – possibly in conversation with Yara, standing near a red car – but there was little more to go on than that. Ruggeri called in tracker dogs: a breed of bloodhound, Segugio Italiano, with short, brown and black hair, long ears, doleful eyes and a keen sense of smell. Instead of following the expected route back to Yara’s home in Via Rampinelli, Ruggeri’s dogs went in the opposite direction, towards a small hamlet nearby called Mapello. When the team analysed the last signals from Yara’s mobile phone, the result showed that it had been registered as present in Mapello at 18.49 that evening. Everything seemed to point away from Yara’s family, but investigations of this type always start at home. Over the next few days, Ruggeri and her team questioned every member of the Gambirasio family, looking for signs of discord or dark secrets. Yara’s parents were well-known and respected: her father, Fulvio, was a large, solid man with thick glasses, an architect whose father had been the local postman, like his mother before him. Maura, Fulvio’s wife, was a teacher in Longuelo, a nearby town. The marriage appeared strong, they had four children: Yara had an older sister, Keba, 15, and two younger brothers, Natan and Gioele, both under 10. Ruggeri put wiretaps on hundreds of phones. Her team also tried to trace the owners of all the handsets – some 15,000 – which had passed through Mapello on the day of Yara’s disappearance. One of these belonged to a Moroccan man called Mohammed Fikri. In one wiretapped conversation, in late November, the interpreter heard the phrase: “Forgive me God, I didn’t kill her”. Fikri had been working in a builders’ yard in Mapello, but by the time investigators had put the pieces together, a few days later, he was on a boat bound for Tangiers. On 4 December, Italian authorities intercepted the vessel and arrested Fikri. They searched the van he had been using and discovered that it contained a blood-stained mattress. “People liked him as the guilty party,” Ruggeri told me ruefully last year, “because he was foreign.” But Fikri was quickly cleared. The phrase had been mistranslated, and the blood was extraneous to the investigation. As autumn slipped into winter, Brembate di Sopra found itself at the centre of a mystery which had captured the country’s imagination. Italian TV is dominated by cronache nere, crime news, and now national camera crews descended. The Gambirasio family were horrified by the sudden glare of publicity. TV cameras became a permanent fixture in their quiet cul-de-sac. The family locked themselves away, lowering their shutters and even turning down the idea of a torchlight procession to raise awareness. Instead, nuns from the Ursuline order, who taught at Yara’s school, came to pray with Maura. A mass was held instead of the procession, and the rare statements from the parents were devout pleas for privacy and patience. The reticence of the Gambirasio family reflected the culture of this region. The province of Bergamo is much closer to Switzerland than Naples and the Bergamaschi are generally more reserved than their southern countrymen. “It’s in the spirit of mountain people to disdain gossip and not to repeat nonsense,” Piero Bonicelli, the editor of Araberara, a colourful local newspaper, told me. “If I don’t know something, if I have only heard it said, I don’t say anything until I’m certain it’s true.” Desperate to discover the whereabouts of their daughter, the Gambirasio family did share some photographs of Yara with the press in the days after her disappearance – Yara queueing to take communion; doing the splits in the gym; a studio photo of her in a yellow top; in an Italy football shirt; on the beach – but no one came forward with any useful information. When her parents finally made a televised appeal, a few days after their first Christmas without Yara, they looked awkward. Maura was so uncomfortable she was, unintentionally, rolling her eyes. Fulvio, who wore a rugby shirt, hesitantly read a plea: “Help us return to normality”. He explained that the family values were “love, respect and honesty”, and that they would be giving no interviews. This wariness towards outsiders owes much to the region’s history. Bergamo is still called, in local dialect, “Bèrghem”, an old name which means “the town of the mountain”. The city has always been a strategically important citadel, one of the last redoubts before the flat, fertile basin of the river Po. The Bergamaschi are used to seeing off invasions. Just a few miles west of Brembate di Sopra is a small town called Pontida, where in 1167 the Lombard League – the alliance of northern Italian cities which joined together to resist the German Holy Roman emperor, Frederick I – was formed. The Oath of Pontida still exerts a symbolic power today. It’s frequently evoked by the separatists of the Northern League to rally sentiment against outsiders: against the perceived indolence and corruption of southern Italy or, more commonly now, against immigrants from developing nations. This setting was part of what fascinated the Italian public about Yara’s disappearance. The province of Bergamo seemed to represent two different sides of the country. Where Lower Bergamo, towards the plains, is fashionable, well-connected and industrialised, Alpine Bergamo is agricultural, remote and deeply traditional, a close-knit place which nurtures suspicion, even superstition. Some locals talk, without irony, of this being a land of streghe, of witches, who steal or poison young children. Yara’s disappearance has continued to grip the Italian public over the past four years, becoming one of the most extraordinary, and sophisticated, criminal investigations in Italian history. “It’s like a novel”, a newspaper editor once told me, shaking his head. When I recently asked Ruggeri, the chief investigator, to sum up the case, she stared at her desk and just said “incredible” four times. * * * On the afternoon of 26 February 2011, exactly three months after Yara disappeared, a middle-aged man named Ilario Scotti was flying his radio-controlled plane in the small town of Chignolo d’Isola, 10km south of Brembate di Sopra. Chignolo is surrounded by industrial estates, and the scrubland by Via Bedeschi seemed like a safe, unpopulated place for Scotti to try out his new model aircraft. The model aeroplane wasn’t functioning as Scotti wanted, though, so he brought it down to earth amid the tall weeds. As he picked up his plane, he caught sight of some rags on the ground nearby. At first, he thought someone had been fly-tipping. Then he saw the shoes. Ruggeri was coming back from a day’s skiing with her daughter when she got the call that a body had been found. She dropped her daughter at home and went straight to the crime scene. The body was in an advanced state of decomposition, but Ruggeri could see the black bomber jacket with its elasticated waist which Yara had been wearing when she left home in November. There, too, was her Hello Kitty sweatshirt. Crime scene investigators found Yara’s iPod and house keys, as well as the sim card and battery for her LG phone. The phone itself was missing. “It was a relief,” Ruggeri told me later. “Yara’s disappearance had really disturbed me – I’m a mother too, and the only thing worse than the death of a child is the disappearance of a child.” The autopsy was conducted by Italy’s most famous forensic pathologist, Professor Cristina Cattaneo. She discovered traces of lime in Yara’s respiratory passages, and the presence of jute, a vegetable fibre used to make rope, on her clothing. Yara hadn’t been raped, although her purple bra was unhooked. She had suffered multiple injuries from a sharp weapon which had pierced her clothing at various points. It seemed that she had been attacked and abandoned. She had died of exposure. The presence of lime and jute suggested the killer might be in the building trade. The forensics team retrieved two DNA samples, one from Yara’s phone battery and the other from two fingers of her black gloves but neither matched any samples the authorities had on record. Two months later, in April, the commander of the scientific investigations department in Parma phoned Ruggeri. “I’ve got good news,” he told her. “This murder has a signature. We’ve found male DNA on the underwear of the deceased.” It was likely that the murderer had himself been wounded in the struggle, leaving his DNA on the girl’s knickers. Ruggeri and her team named the murder suspect Ignoto 1, “Unknown 1”. Now the hunt for Yara’s killer could begin in earnest. The workload was huge, and Ruggeri divided up the duties: the police were responsible for taking DNA samples from family members, from school friends and people in the gym; the carabinieri concentrated on the phone records, cross-referencing all the mobile phones that had moved from Brembate di Sopra to Chignolo d’Isola on 26 November 2010. Each phone user whose number appeared in both cells was tracked down and asked for a DNA sample. It was slow and laborious work. It took geneticists in Parma, Pavia and Rome a minimum of six hours to transform just a few samples of DNA into something which could be read, and compared, on a computer screen. The cost, in machinery and manpower, was immense and the investigation would go on to become one of the most expensive manhunts in Italian history. Yara’s funeral took place on a hot morning in late May 2011. Onlookers applauded the white coffin, which was topped with a huge bouquet of white flowers, as the hearse slowly drove towards her gym. The ceremony took place in the sports hall where she had spent so many hours training, and where she had last been seen alive. Outside, a large crowd watched the funeral on a giant screen, and heard the condolences of Giorgio Napolitano, the president of the Republic. By the time of the funeral, investigators had taken thousands of DNA samples but they still had no leads. Close to the scrubland where Yara’s body had been found was a nightclub called Sabbie Mobili (Quicksand). Ruggeri knew that murderers tend to dump bodies in areas with which they’re very familiar, so although it seemed like a long shot, in spring 2011 investigators started taking DNA samples outside the club on busy Fridays and Saturdays. Sabbie Mobili had a reputation for violence – a young man from the Dominican Republic had been murdered outside its doors on 16 January 2011 – but the club had helpful records. Clubbers required a membership card to get in, and so the authorities could easily track down anyone who went there regularly. Ruggeri finally got a break. One of the samples from Sabbie Mobili seemed strikingly similar to the suspect, Ignoto 1. The man who gave the sample was called Damiano Guerinoni. He was quickly excluded as a suspect – he had been in South America on the day of Yara’s disappearance – but geneticists were convinced he was a close relative of the murderer. “We were all very excited”, Ruggeri told me. “We said, ‘bingo – just a couple of more days’ [and we’ll have the murderer].” As Ruggeri and her team put together the jigsaw of Guerinoni’s family, they made an astonishing discovery: Damiano Guerinoni’s mother, Aurora Zanni, had worked for 10 years as a domestic help in the Gambirasio home. She lived nearby, and had gone to Yara’s home twice a week throughout the young girl’s childhood. Ruggeri resigned herself to the fact that it was just a coincidence. ‘You couldn’t make it up. This whole case is crazy’ Zanni was a middle-aged woman who was very attached to her employers. She recalled how Yara would always ask her to watch her latest gymnastics moves, and Zanni would tell her to be careful not to hurt herself. In 2011, she was no longer working for the family but said her relationship with Yara’s parents was excellent. To find herself at the centre of the investigation into Yara’s murder was, Zanni said later, “the worst thing that could happen to me”. “Obviously,” Ruggeri says, “we intercepted [Damiano Guerinoni and Aurora Zanni’s] calls, had them followed, grilled them and tortured them, in the sense that we pressed them.” It was only after months of close surveillance that Ruggeri, in the summer of 2011, resigned herself to the fact that “it was just a crazy coincidence”. “There was no connection”, she says. “You couldn’t make it up. This whole case is crazy.” Having seemed so close to a resolution, Ruggeri’s team reluctantly discarded the angle of the domestic help. The only promising lead they still had was the fact that Damiano Guerinoni’s DNA was so similar to that of Ignoto 1. * * * A year on from Yara’s murder, Ruggeri’s team was now under intense pressure to find the killer. Thousands of people were being DNA tested and some locals who hadn’t been approached for a sample suggested to the press that the investigation was haphazard. Politicians made personal attacks on Ruggeri. One Northern League politician, Daniele Belotti, publicly decried her incompetence, writing an open letter in January 2012 to the minister of justice asking for her to be replaced by someone “of proven experience”. (Ruggeri filed a lawsuit against Belotti for libel on 20 April 2012, taking particular objection to his characterisation of her as a person of “low technical and moral profile”.) Behind these criticisms of Ruggeri was a strong undercurrent of sexism: what hope was there that this woman could solve such a complex crime? She was unconventional, a single-mother with long salt-and-pepper hair, and five earrings in her left ear. She played classical guitar, rode to work on an old Vespa and had a blackbelt in karate. Ruggeri felt she was also being targeted because she had decided to drop the case against the Moroccan labourer, Mohammed Fikri. “Many people thought I had made the wrong decision”, Ruggeri told me, “and they held it against me. The criticism was ferocious … I found it very tough.” Ruggeri decided to concentrate on the only promising lead she had: the Guerinoni DNA. Her team spent months recreating the Guerinoni family tree. When I visited her office last year, Ruggeri pulled out a folder and showed me hundreds of names, each one annotated: dates of birth, places of birth, relationships within the family. The investigators had worked out a complete genealogical tree as far back as 1815, with other branches of the family going back as far as 1716. The roots of that family tree were in the small village of Gorno. It’s only 45 minutes’ drive north of Bergamo itself, up the narrow Seriana Valley, but it feels like another world. You arrive through a series of hairpin bends, into a village that smells of woodsmoke and chickens. In the distance, you can hear the sound of waterfalls and cowbells. The village is full of narrow flights of steps – the only horizontal patch of land is a sandy five-aside football pitch. Although only 1,600 people live in Gorno and it seems like a quiet, pious place, according to one former parish, the village is “a bit too hot, in every sense. Let’s say they’re a bit promiscuous.” In 2011 two people in Gorno were murdered in unrelated incidents. The same families have been here for centuries, and on the village’s war memorial, outside the small church, the names of Benedetto and Pietro Guerinoni are carved into the stone. The Guerinoni family were nicknamed i Fantì, the “infantry”: considered by everyone to be loyal, strong, even hot-headed. Damiano Guerinoni’s father had a brother, Giuseppe, who had died in 1999. Investigators visited Giuseppe’s widow in September 2011 and found two stamps he had licked: one in order to validate his driving licence and another on a postcard he had sent to his family. When DNA results came back from that sample, they had another breakthrough: geneticists were convinced that Giuseppe Guerinoni was the father of Ignoto 1, the suspected murderer. Ruggeri’s team quickly built up a picture of Giuseppe Guerinoni and his family. Giuseppe himself, a thick-set man with a rugged face, had been a bus driver who played the accordion at village festivals. His marriage, to Laura Poli, had seemed conventional. They had three children: a girl and two boys. Laura had become a Jehovah’s Witness, and after her husband’s death had moved to a nearby town, Clusone. Since Ignoto 1 was male, investigators concentrated on the sons, Pierpaolo and Diego. Pierpaolo was, like his mother, a Jehovah’s Witness; Diego had a drug problem. Neither provided a perfect match with Ignoto 1, however, and neither of them had children. If Ignoto 1 really was the son of the late Giuseppe Guerinoni, the only explanation was that, somewhere out there, was his illegitimate child. “It became,” Ruggeri says, “an investigation within an investigation.” She was now hunting a woman, presumably in middle- to old-age, who 30 or 40 years ago had had an affair with a married man, now long dead, and given birth to a boy who went on to murder Yara Gambirasio. * * * It proved extremely difficult for investigators to penetrate the mountain villages – Ponte Selva, Parre, Clusone and Rovetta – where they were looking for clues and leads. Some Italian journalists spoke of the “cocciutaggine”, or pig-headedness, of the Bergamo Alps – a caricature which only served to antagonise the already defensive locals. “The people here,” says Bonicelli, the editor of Araberara, “were irritated by the stereotype of highlanders closed in on themselves. The word “omertà” was even used, which implies [the silence of] Sicily and the mafia. It was deeply offensive.” There was incomprehension on both sides. The investigation was, by Italian standards, unusually secretive. Locals couldn’t understand why police hunting the murderer of a 13-year-old girl were taking DNA samples of elderly women. Bonicelli – a fan of the fictional detectives Maigret and Montalbano – says that the investigation “was lacking the traditional, human element: the sort of person who goes into a bar in the village … and puts someone at ease so that something slips out.” Locals felt there was something cold about this investigation, with its invasive demands for DNA samples. And it was changing the atmosphere in these small communities. People thought, says Bonicelli, “that the murderer was here, amongst us. So there was a sort of – not panic, but fear.” Investigators knew that from the early 1960s onwards, for two weeks every May, Giuseppe Guerinoni used to go to a spa resort called Salice Terme, south of Milan, without his wife. Throughout the spring of 2012, Ruggeri’s team scoured records and registers, tracking all the women who had stayed in the resort at the same time of year as Guerinoni. They searched orphanages and homes for “fallen women”; they tested single mothers and women who had left the mountains for lower Bergamo. They came up empty-handed. The woman they were looking for, they realised, was probably neither single nor “fallen”, but hidden behind the walls of a marriage. Divorce was only legalised in Italy in 1970 – until that time many couples had stayed together despite infidelities. By the time Ruggeri was searching for Ignoto 1’s mother, Yara’s parents had hired their own expert, a freelance geneticist, in order to review the investigation and explain it to them. For almost a year Giorgio Portera lobbied for the exhumation of Giuseppe Guerinoni’s body from the cemetery in Gorno. He was concerned that investigators has only been able to compare 13 Short Tandem Repeat (STR) regions, which are sequences of DNA, with the DNA of Ignoto 1. Confirmation of paternity demands that at least 15 STR regions be compared. So early on 7 March, 2013, workmen chiselled into Guerinoni’s loculo, the horizontal slot in a cemetery wall where his coffin was kept, and removed his remains. They were transferred by carabinieri to the Papa Giovanni XXIII hospital in Bergamo for examination before being returned to Gorno just a few hours later. A couple of camera crews, and a few bewildered villagers, watched. When DNA was extracted from his remains, 29 STR regions could be compared. It was now absolutely certain that Guerinoni was the father of Ignoto 1. As the investigation dragged on through 2013, the public slowly became aware of why a woman was being sought. It became common knowledge that the late Giuseppe Guerinoni had had a lover, and that she was thought to be the mother of the murderer. “We have rediscovered,” wrote one journalist, “that accursed desire for gossip which spices up small-town life. Now, here, everyone wants to know whose son so-and-so is.” Long-forgotten infidelities and old suspicions surfaced. Bonicelli laughs as he describes how his journalists discovered five illegitimate children in two small villages: “Five! We could have started a gossip magazine. It was like an open sewer: we were receiving anonymous letters, stories, people telling us about backgrounds and cuckolds.” A society which had always prided itself on its sense of loyalty and traditional Catholicism, suddenly discovered the betrayals in its midst. “Perhaps the point is this,” Bonicelli wrote in an editorial, “we don’t know each other any more.” * * * Until this point, the investigation had been characterised by cutting-edge, scientific analysis, but it was an old-fashioned detective who broke the case open. Marshall Giovanni Mocerino was Ruggeri’s right-hand man, working in the office next to hers. His desk is covered in hundreds of scraps of paper, scrawled with names and numbers in different coloured inks. Mocerino has bushy grey hair and black-rimmed glasses and speaks in a light-hearted, informal manner. But he’s also, by his own admission, a capotosta, a stubborn man: “I get fucked off when I can’t solve a case,” he told me. Because of this case, he said, “I haven’t had a holiday for four years.” Although Mocerino was born in the south, near Naples, he had lived in the Bergamo Alps area since 1983 and he had come to know the region well. He was always talking with local people, and “sensitised”, as he said, thousands to the case. He reminded them that, amid all the gossip about infidelities that had been sparked off by the hunt for Guerinoni’s lover, a young girl had been killed. By 2013, he knew everything about Guerinoni’s life: born in Gorno, Guerinoni had moved in the mid-1960s to Ponte Selva, a nearby settlement which had grown up around the bridge over the Serio river. He drove a public bus for the Motallini (later SAB) bus company. In the 1960s and 70s he would have driven plenty of young women to and from jobs in the various textile factories. Mocerino questioned Guerinoni’s fellow bus drivers, one of whom had already gone to the press in March 2013 saying that Guerinoni had confessed to having got a young woman “in trouble”. Another former colleague described Guerinoni as a “man” with a “capital M”, implying that he was a womaniser. But it wasn’t until June 2014, that one of Mocerino’s sources finally gave him the name he was looking for. Mocerino has always protected his sources, and refuses to confirm who first whispered the name of the mystery woman to him but however it came about, investigators had the final piece of the jigsaw: Ester Arzuffi. Arzuffi had been a neighbour of Guerinoni’s in Ponte Selva in the late 1960s. In 1966, aged 19, she had married Gianni Bossetti from Parre, a nearby village. Bossetti was a man whose tough life had turned him inwards: he had been orphaned young and suffered from psoriasis, arthrosis and depression. Arzuffi seemed very different: an outgoing, good-looking woman, she wore short skirts and dyed her hair. She got a job at the textile factory a few miles away in Villa d’Ogna, and took the bus every day. Ruggeri’s team immediately cross-checked the DNA samples they had, and discovered that Arzuffi had already been tested in July 2012. They double-checked, and realised that a basic error had been made by a geneticist in Rome – Arzuffi’s DNA had been compared not to Ignoto 1’s, but to Yara’s. Now investigators hurriedly reran the test and discovered that Arzuffi was, indeed, the woman they had spent so long looking for. She was the mother of Ignoto 1. Arzuffi had left Ponte Selva in 1970, but she had continued her affair with Guerinoni, and in the autumn of 1970 she gave birth to twins – a boy and a girl. The boy was called Massimo Bossetti (his middle name was Giuseppe, like his biological father). A slim boy who loved to party, he was nicknamed “the animal” by his friends. He was now 42, a builder, married with three children and living in Mapello, the hamlet near Yara’s hometown where the last signal from Yara’s cell phone had been recorded on 26 November 2010. He was short, with piercing blue eyes, and had a peroxided, pencil goatee. Ruggeri moved fast. On 15 June 2014, she set up a fake roadblock breathalysing drivers. When her police officers stopped Massimo Bossetti, they pretended the machine hadn’t worked the first time, so they could get two good samples. His DNA was immediately sent for overnight tests and results showed it was an exact match with Ignoto 1. One geneticist told me that the chance of a random match between Ignoto 1 and Massimo Bossetti was 2 x 10-27. Ruggeri wanted to observe Bossetti before arresting him, to study his movements and behaviour from a distance, but she was also worried that the news would get out and that he might leave town. On 16 June, Bossetti was arrested and charged with the murder of Yara Gambirasio. The Italian home secretary himself released a statement announcing his arrest. Reaction in the mountains of Bergamo, centre of the investigation, was relief: the murder suspect was from lower Bergamo. The suspect's internet history
was troubling, using search
words which implied a compulsion
for pubescent young girls Investigators discovered plenty of circumstantial evidence. Bossetti had frequently hung around Yara’s house; he parked his car in Via Don Sala, behind the gym, and ate at the Toscanaccia pizzeria at the end of her road. He had gone for regular UV showers at a tanning shop nearby. His internet searches were troubling, using search words which implied a compulsion for pubescent young girls. More pertinently, records suggested that his phone had been present in Brembate di Sopra on the evening of Yara’s disappearance, but had been switched off from 5.45pm until the following morning at 7.34am. For Ruggeri, the arrest was the reward for almost four years of dogged investigative work. After enduring a barrage of criticism for alleged incompetence, she was now feted for her brilliance. The case is likely to come to trial this spring. Bossetti maintains his innocence, and his lawyers are planning to contest the DNA evidence, claiming that DNA merely indicates “presence, not responsibility”. Meanwhile, three families are dealing with the devastation of the case. Guerinoni’s widow has been forced, in the autumn of her life, to come to terms with her husband’s infidelity and the existence of his other children. Meanwhile, just as he was diagnosed with terminal cancer, Giovanni Bossetti became the nation’s most famous cuckold, learning at the same time as the rest of the country that none of his three children are his (leaks from the investigation revealed that Ester Arzuffi’s third child, Fabio, also had a different father). The marriage of the accused, Massimo Bossetti, has also come under strain: since his defence sought to portray him as a family man, two people have come forward to claim that they had affairs with his wife. Such is the local loathing for Bossetti that since his arrest, his twin sister – herself coming to terms with both her brother’s fate and the fact that the man she thought was her father is not biologically related to her – has twice been beaten up. Her mother, Ester Arzuffi, still denies that she’s ever been unfaithful to her husband. The Gambirasio family, meanwhile, has remained private. Recently, awarding a gymnastics trophy named after her daughter, Maura Gambirasio struggled to smile and made no public comments. She’s cut her hair short and looks gaunt. Yara is buried between her two grandparents in a cemetery just across the road from her gym. There’s no date on her tombstone, only a signature next to a photograph of her wearing a white alice band. All around the grave are mementoes left by her friends: gym shoes, a metal tulip, rag dolls, plastic angels and little bracelets. Often, in the early evening, you see Yara’s father, Fulvio, standing here, gazing at the resting place of his parents and his daughter.
Zdroj: Guardian UK
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What Doctors Can Tell About Your Health Just By Looking At Your Eyes
If seeing well isn't enough of a priority, here's a better reason to get your vision checked regularly: A third of all known genetic syndromes can affect your eyes.
In the video below, from National Geographic , Dr. Neal Adams lists the gamut of systemic disorders — diseases that affect the entire body — that ophthalmologists can detect during a simple eye exam.
Your eyeballs can show signs of diabetes, nutritional deficits, cardiovascular disease, and nerve damage, to name a few.
Here are some of the things ophthalmologists look for during an exam.
Abnormally shaped or colored blood vessels can show signs of cardiovascular disease such as high blood pressure. Ophthalmologists can even see individual red blood cells flowing through the capillaries — tiny blood vessels — in the eye.
National Geographic
Stress can take a toll on your eyes, just as it can on the rest of your body. According to Adams, "Stress causes cells behind the eye to leak fluid, like having a blister in the retina." Here's what that painful-sounding disorder can look like:
National Geographic
In the eye below, a brown halo surrounds the pupil — the opening at the center of the eye that looks black — a disorder called posterior synechia. The condition occurs when the colored part of the eye, called the iris, gets attached to the eye's lens, which lies through the pupil. It's often an indicator of inflammation elsewhere in the body.
National Geographic
Zdroj: Business Insider
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Being lazy could be genetic, scientists say
A mutation in a gene with a critical role in the brain could explain why some people are "couch potatoes" according to researchers. Scientists in China and Scotland have made what is being called a "key discovery", which centres on the system that regulates physical activity levels. The teams are hopeful that the study could help "millions of patients". Based on the findings published in the journal 'PLOS Genetics', pills could be developed in the future which would motivate those who are less inclined to exercise. While the experiments were conducted on mice, 400 overweight Chinese patients were also screened for metabolic syndrome, with scientists finding that two of them had mutations in the gene. To make their discovery, scientists compared normal mice with those that had a mutation in a gene called SLC35D3, and found that it produces a protein which plays a key signalling role in the brain's dopamine system, affecting the regulation of physical activity. Mice with this gene had far fewer of this type of dopamine receptor on the surfaces of their brain cells. It was instead stuck within in the cell, leaving the signal process unable to function. But when the affected mice were treated with a drug that activates dopamine receptors, the problem was reversed and the mice became more active and lost weight. Study leader Professor Wei Li, of the Institute of Genetics and Developmental Biology (IGDB) in Beijing, said he was excited about the findings. "We discovered that mice with this gene mutation were typical couch potatoes," he said. "They walked only about a third as much as a normal mouse, and when they did move they walked more slowly. "The mice became fat and they also developed other symptoms similar to a condition in people called metabolic syndrome - a medical term for those with a combination of risk factors related to diabetes, high blood pressure and obesity," he explained. He added that the discovery could signal a change in attitudes towards obesity. "A long-standing prescription in combating obesity is to mind your mouth and move your legs. However, genetics contributes to the reluctance to move in some obese people. Medical treatments will in the future be tailored to fit a person's individual genetic make-up." Co-author of the research paper Professor John Speakman, who works between the University of Aberdeen and the IGDB, said: "Although only about one in 200 people may have these "rare" mutations, there are a very large number of people worldwide that have metabolic syndrome. Consequently, the population of sufferers that may benefit from being treated with dopamine receptor drugs runs into many millions of patients."
Zdroj: web
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Baffling 400,000-Year-Old Clue to Human Origins
Scientists have found the oldest DNA evidence yet of humans’
biological history. But instead of neatly clarifying human evolution,
the finding is adding new mysteries.
In a paper in the journal Nature, scientists reported
Wednesday that they had retrieved ancient human DNA from a fossil
dating back about 400,000 years, shattering the previous record of
100,000 years.
The fossil, a thigh bone found in Spain, had
previously seemed to many experts to belong to a forerunner of
Neanderthals. But its DNA tells a very different story. It most closely
resembles DNA from an enigmatic lineage of humans known as Denisovans.
Until now, Denisovans were known only from DNA retrieved from
80,000-year-old remains in Siberia, 4,000 miles east of where the new
DNA was found.
The mismatch between the anatomical and genetic
evidence surprised the scientists, who are now rethinking human
evolution over the past few hundred thousand years. It is possible, for
example, that there are many extinct human populations that scientists
have yet to discover. They might have interbred, swapping DNA.
Scientists hope that further studies of extremely ancient human DNA will
clarify the mystery.
“Right now, we’ve basically generated a big question mark,” said
Matthias Meyer, a geneticist at the Max Planck Institute for
Evolutionary Anthropology in Leipzig, Germany, and a co-author of the
new study.
Hints at new hidden complexities in the human story
came from a 400,000-year-old femur found in a cave in Spain called Sima
de los Huesos (“the pit of bones” in Spanish). The scientific team used
new methods to extract the ancient DNA from the fossil.
“This
would not have been possible even a year ago,” said Juan Luis Arsuaga, a
paleoanthropologist at Universidad Complutense de Madrid and a
co-author of the paper.
Finding such ancient human DNA was a major
advance, said David Reich, a geneticist at Harvard Medical School who
was not involved in the research. “That’s an amazing, game-changing
thing,” he said.
Since the 1970s, Spanish scientists have brought out a wealth of
fossils from the cave dating back hundreds of thousands of years. “The
place is very special,” said Dr. Arsuaga, who has found 28 nearly
complete skeletons of humans during three decades of excavations.
Based
on the anatomy of the fossils, Dr. Arsuaga has argued that they
belonged to ancestors of Neanderthals, which lived in western Asia and
Europe from about 200,000 to 30,000 years ago.
When Dr. Meyer and his colleagues drilled into the femur, they found ancient human DNA inside, just as they had hoped.
“Our expectation was that it would be a very early Neanderthal,” Dr. Meyer said.
But the DNA did not match that of Neanderthals. Dr. Meyer then
compared it to the DNA of the Denisovans, the ancient human lineage that
he and his colleagues had discovered in Siberia in 2010. He was shocked
to find that it was similar.
“Everybody had a hard time believing it at first,” Dr. Meyer said. “So we generated more and more data to nail it down.”
The extra research confirmed that the DNA belonged on the Denisovan branch of the human family tree.
The
new finding is hard to reconcile with the picture of human evolution
that has been emerging based on fossils and ancient DNA. Denisovans were
believed to be limited to East Asia, and they were not thought to look
so Neanderthal-like.
Based on previously discovered ancient DNA
and fossil evidence, scientists generally agreed that humans’ direct
ancestors shared a common ancestor with Neanderthals and Denisovans that
lived about half a million years ago in Africa.
Their shared
ancestors split off from humans’ lineage and left Africa, then split
further into the Denisovans and Neanderthals about 300,000 years ago.
The evidence suggested that Neanderthals headed west, toward Europe, and
that the Denisovans moved east.
Humans’ ancestors, meanwhile,
stayed in Africa, giving rise to Homo sapiens about 200,000 years ago.
Humans then expanded from Africa into Asia and Europe about 60,000 years
ago. They then interbred not only with Neanderthals, but with
Denisovans, too. Later, both the Denisovans and Neanderthals became
extinct.
“Now we have to rethink the whole story,” Dr. Arsuaga said.
Dr.
Arsuaga doubts that Denisovans were spread out across so much of the
Old World, from Spain to Siberia, masquerading as Neanderthals.
One
alternative explanation is that the humans of Sima de los Huesos were
not true Neanderthals, but belonged to the ancestors of both Denisovans
and Neanderthals.
It is also possible that the newly discovered
DNA was passed to both Neanderthals and Denisovans, but eventually
disappeared from Neanderthals, replaced by other variants.
“It got
lost in one lineage but made its way in the other,” suggested
Jean-Jacques Hublin, a Max Planck paleoanthropologist who was not
involved in the research.
Beth Shapiro, an expert on ancient DNA
at the University of California, Santa Cruz, favors an even more radical
possibility: that the humans of Sima de los Huesos belong to yet
another branch of humans. They might have been a species called Homo
erectus, which originated about 1.8 million years ago and became extinct
within the last few hundred thousand years.
“The more we learn from the DNA extracted from these fossils, the more complicated the story becomes,” Dr. Shapiro said.
This complicated story has come to light only because of advances over the past 20 years in retrieving ancient DNA.
When
an organism dies, its DNA breaks down into smaller and smaller
fragments, while also becoming contaminated with the DNA of other
species like soil bacteria. So piecing the fossil DNA together is a bit
like putting together a jigsaw puzzle created by a sadist.
In
1997, Svante Paabo of the Max Planck Institute and his colleagues, who
had pioneered the techniques for retrieving DNA fragments, published
a snippet of DNA from a Neanderthal fossil dating back about 40,000
years. They and other scientists then built on this success by searching
for bits of DNA from other Neanderthals.
In 2006, a team of French and Belgian researchers obtained a fragment of Neanderthal DNA dating back 100,000 years, which until now held the record for the oldest human DNA ever found.
Meanwhile, using improved methods, Dr. Paabo, Dr. Meyer and their colleagues assembled a rough draft of the entire Neanderthal genome in 2010.
That
discovery shed light on how Neanderthals and humans’ ancestors split
from a common ancestor hundreds of thousands of years ago. It also
revealed that Neanderthals and humans interbred about 50,000 years ago .
Around
the same time as that discovery, Russian collaborators sent the Max
Planck team 80,000-year-old fossils they had found in a cave in Siberia
called Denisova. When the German scientists sequenced the entire genome
from the finger bone of a girl, it turned out to be neither human nor
Neanderthal, but from a separate lineage , which Dr. Paabo and his colleagues named Denisovans.
Dr.
Meyer is hopeful that he and his colleagues will be able to get more
DNA from the Spanish fossil, as well as other fossils from the site, to
help solve the puzzle they have now stumbled across. “It’s extremely
hard to make sense of,” Dr. Meyer said. “We still are a bit lost here.”
Zdroj: The New York Times
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How was Angelina Jolie's breast cancer risk calculated?
Yesterday Angelina Jolie shared her experience as a carrier of a BRCA1 genetic mutation that confers a very high lifetime risk of developing invasive breast cancer . New Scientist spoke to breast cancer specialist Allison Kurian , of Stanford University in California who has developed a tool that enables women to determine how different treatment options can reduce their overall risk .
For carriers of a BRCA1 mutation, the lifetime risk for invasive breast cancer is 65 per cent. What is that based on? It's
based on very large studies of thousands of women. When we're
counselling people, we give them average numbers because they're the
most robust.
Angelina Jolie said her lifetime risk was 87 per cent, where did that figure come from? That 87 per cent number is from some of the earlier studies. The BRCA1 and BRCA2
genes were discovered in the mid-90s and the earliest research mostly
studied very striking families who came to doctors because everybody had
cancer. When you look at those families, you're going to make a very
high estimate of risk. But then when you do bigger studies, the average
risk is lower.
So that 87 per cent figure is probably not a calculation of her personal risk? I
am not involved with her care, but I doubt it's a personal assessment. I
see that number often and in general think of it as coming from
slightly older, smaller studies. Most of us in this field tend to use
the newer numbers from the larger studies.
From that 65 per cent average, what makes an individual carrier of a BRCA1 mutation more or less likely to get breast cancer? That's the million-dollar question. There's great interest in understanding why one person with a BRCA1 mutation might develop cancer in their 30s whereas another might never get cancer at all.
But if a woman has a BRCA1
mutation and most of her relatives have developed very early breast
cancer, I worry about her a little bit more than a woman in a family
with a BRCA1 mutation where, for whatever reason, they don't seem to have as many cancers.
Is there a way to accurately calculate someone's individual lifetime risk of developing invasive breast cancer? I don't think we're quite there yet. The BRCA decision tool we developed makes the average estimate based on large numbers, because that is the safest thing to do.
The tool then compares different
options a person might choose. For example, one might choose preventive
mastectomy, like Angelina Jolie did; other women might choose a very
intensive screening strategy. Our tool helps to compare those different
options and what they would provide in terms of survival and quality of
life.
Angelina Jolie wrote in The New York Times that her double mastectomy cut her risk of getting breast cancer to 5 per cent . Is that typical of women who undergo this procedure? That
would be about right. Most of the studies estimate that whatever a
person's risk might be, the surgery will reduce that risk by 90-95 per
cent. If her risk was about 65 per cent you're going to get down to a
single digit number.
Not everyone currently has access to – or can afford – BRCA screening tests. Do you think they should be offered to all women? I'd
certainly like to see expanded access to healthcare of all kinds. But I
don't think that every woman needs to be tested for BRCA mutations
because they're rare. On average, if you pull people in off the street,
about one in 400 would carry a BRCA mutation.
But I think when there are red flags –
like early breast cancer, multiple breast cancers, ovarian cancer or
male breast cancer – all of those families should be offered genetic
testing.
As a geneticist specialising in breast cancer, were you glad to see Angelina Jolie share her experience of being someone with a BRCA1 mutation? Absolutely,
I think she was extremely courageous. I think it greatly increases the
opportunity that we would diagnose people who are at high risk and offer
them life-saving interventions. I'm very impressed; it's a very
generous thing to do.
Zdroj: New Scientist
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Meditation boosts genes that promote good health
Feeling run-down? Try a little chanting, or meditation
– seriously. Such relaxation techniques can boost the activity of genes
involved in several processes beneficial to health, and they only take a
few minutes each day to show results.
Previous studies have reported changes to the brain
while people practise these activities, but a new study shows for the
first time that gene activity changes too. This could explain the
reported beneficial effects of meditation , yoga and prayer .
"It's not New Age nonsense," says
Herbert Benson of the Massachusetts General Hospital in Boston. He and
his colleagues analysed the gene profiles of 26 volunteers – none of
whom regularly meditate – before teaching them a relaxation routine
lasting 10 to 20 minutes. It included reciting words, breathing
exercises and attempts to exclude everyday thought.
After eight weeks of performing the
technique daily, the volunteers gene profile was analysed again.
Clusters of important beneficial genes had become more active and
harmful ones less so.
The boosted genes had three main
beneficial effects: improving the efficiency of mitochondria, the
powerhouse of cells; boosting insulin production, which improves control
of blood sugar; and preventing the depletion of telomeres, caps on
chromosomes that help to keep DNA stable and so prevent cells wearing
out and ageing.
Clusters of genes that became less active were those governed by a master gene called NF-kappaB ,
which triggers chronic inflammation leading to diseases including high
blood pressure, heart disease, inflammatory bowel disease and some
cancers.
Within minutes
By taking blood immediately after
before and after performing the technique on a single day, researchers
also showed that the gene changes happened within minutes.
For comparison, the researchers also
took samples from 26 volunteers who had practised relaxation techniques
for at least three years. They had beneficial gene profiles even before
performing their routines in the lab, suggesting that the techniques had
resulted in long term changes to their genes.
"It seems fitting that you should see
these responses after just 15 to 20 minutes just as, conversely, short
periods of stress elevate stress hormones and other physiological
effects that are harmful in the long term," says Julie Brefczynski-Lewis
of West Virginia University in Morgantown, who studies the
physiological effects of meditation techniques. "I hope to see these
results replicated by other groups."
"We found that the more you do it, the
more profound the genomic expression changes," says Benson. He and his
colleagues are now investigating how gene profiles are altered and
whether these techniques could ease symptoms in people with high blood
pressure, inflammatory bowel disease and multiple myeloma, a type of
bone marrow cancer.
Benson stresses that the relaxation
techniques should only be an adjunct to conventional medicine and
surgery, not a replacement.
Journal reference: PLoS One , doi.org/mfj
Zdroj: New Scientist
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Genetics demystified
Every physical feature you have, you have your parents, grandparents,
aunts, uncles and a bunch of ancestors to thank for. Likewise, certain
health conditions too can be inherited through those unique genes you
got from mom and dad. Fortunately (and sometimes not so), environment
strongly influences which of your specific (read unique) genetic traits
actually reach their potential. So any trait, good or bad may not ever
become visible in you because of your lifestyle choices, environment and
other outside factors. You may have the gene of a basketball player but never grow to your full
height if you were under-nourished as a child. You may have a long
ancestry of heart disease but if you ate healthy, were physically
active, and chose not to smoke or drink through your lifetime, you may
never run into heart problems. Predictive genetic tests will tell you what disorders run “in the family”, your risk of getting them before symptoms appear. DNA
is not destiny. It is what you choose to make of it. Personal genomics
and its role in lifelong wellness is at least two tiered — personalised
medicine and personalised nutrition. Let’s discuss personalised
nutrition further. Personalized nutrition or DNA diet Says
a young mom: “Scrambling in the kitchen to make one wonder meal that
pleases the taste buds of a husband and two kids, I marvel at my mom who
whipped up multiple meals that catered to all of our tastes as
children.” At a restaurant every person at your table orders a different
meal. If each of you liked to eat different things, could it be that
your body might also ‘want’ or ‘need’ different foods? Now fast-forward
again to year 2020. You are at a restaurant and order biryani. The
waiter does not check if you want it mild or spicy anymore. Instead he
says, “Can you place your finger here, sir? I’ll just scan your genetic
profile.” For what? So that your biryani is cooked with the
right meat and ingredients, oil and flavour best suited for your body.
Your taste alone is not unique, so are your genes which are the
blueprint of your body. Your DNA goes beyond identity; it is the unique
code that decides your metabolic rate, your body composition and puts
you at high/low risk to various diseases. This really is not as far
fetched as it sounds. It’s exactly as far-fetched as airplanes sounded
in 1880 when only birds could fly. Have you wondered why your
friend who follows the same diet as you loses weight faster? Well, it is
partly dependent on your metabolism and body composition. Your genes
determine your metabolic rate, i.e., your ability to digest
carbohydrates, fats etc. Which is why, one diet does not fit all. It
needs to be customised based on your body, your DNA and your lifestyle.
Personalised nutrition is finally here and will create life-altering
options for us in the near future. What’s in it for me? So, is DNA what we are born with and is there no way of changing it? Not at all, DNA is all about what you make of it. Genes
make up the blueprint of the human body, and this is what governs the
personality, growth, health, development and functioning. Certain
portions of DNA are unique to each individual. It is common knowledge
that DNA profiling is one method of establishing identity of an
individual. But DNA goes beyond identity; it is the unique code that
puts an individual at high/low risk to various diseases. Then isn’t it
obvious it plays a crucial role in the cure to your ailments too? Would
you agree it can play a crucial role in managing your lifelong wellness
and wellbeing? So, can we conclude that DNA is what we are born
with and there is no way of changing it? No, DNA is all about what you
choose to make of it. DNA assessment You
might wonder and worry that your parents have diabetes, and since it is
genetic, you are likely to get the disease as well. Not really. Yes,
the chances of you getting diabetes are high, but you could alter the
age at which you get the same, or how your body reacts to the condition.
Here is an actual opportunity to take a good look at your life,
introspect, and take some decisions that will help change the course of
your health. Your DNA could be a one-stop ticket to determine several of
your choices in life beyond just health and wellbeing. By
starting young it is possible to gift ourselves a healthy long life that
each one of us truly deserves. In fact, children as young as five years
of age can have a genetic assessment conducted. Your DNA could become
your ticket, your identity to a better tomorrow. India and lifestyle related diseases * India has an enormous diabetic population (60+ million) of which 90-95 per cent have Type 2 diabetes. *
Indians have a strong link between the increased risk of Type 2
diabetes and the * TCF7L2 gene variation. Nearly 20 per cent diabetics
in India have two copies of the TCF7L2 risk variant. * Cardio
Vascular Diseases (CVDs) easily account for 20 per cent of the overall
outlay of all medical, hospital and insurance spending.
Zdroj: web
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Israeli doctors go back to school for refresher genetics course
The field has moved from the laboratories, where gene therapies have been developed, to clinical settings where they can help diagnose and treat diseases - if the treating physician knows how. The first course of its kind in Israel opened last week at Beilinson Hospital to train doctors from various specialties in medical genetics, a field that has moved from the laboratories where gene therapies have been developed, to clinical settings where they can help diagnose and treat diseases - if the treating physician knows how. The first students in the four-day course are 15 doctors on staff at Beilinson, not necessarily researchers. They are taking the course during working hours at no cost to them. Tel Aviv University's Sackler School of Medicine is considering joining the project, which will mean it can be expanded to additional hospitals. "Many doctors encounter genetics for one semester early in their studies and finish their specialization 10 years later without the up-to-date genetic knowledge that is essential today for the diagnosis and treatment of many illnesses," says Dr. Idit Maya, a senior physician at the Raphael Recanati Genetic Institute at Beilinson, who initiated the new school. Medical genetics is a specialty that is studied for two and a half years by physicians who are already specialists in their fields. Until two years ago, the studies were open only to physicians who had already specialized in internal medicine, pediatrics or gynecology, while other specialists, such as family physicians, oncologists and opthamologists, were not eligible. Now, any specialist may further specialize in genetics. However, this is far from the situation elsewhere in the Western world, where physicians may chose genetics as their primary specialty after only two years of working in the field, and finish their specialization after a four-year residency. Physicians in other specialties can learn from various sources about tests and imaging pertinent to their field. But in genetics, Maya says, physicians who want to learn more about genetic tests to recommend to patients have had no organized course of studies to which they can apply. Maya says doctors should know how genetic mutations can affect a patient's response to the medications they prescribe, a field known as pharmacogenetics. Certain mutations, some of which are common in the general population, can significantly change the way a medication acts in the body and the way the body breaks it down and secretes it. Such mutations can affect the dosage a physician prescribes, Maya adds. For example, before taking the immunosuppressive drug Azathioprine to treat autoimmune disease, a test is now recommended to determine whether the patient is one out of every 300 people in the general population whose have a defect in a gene known as TPMT and whose lives could be endangered by taking the drug. And the livers of people with a certain genetic mutation known as polymorphism might be unable to break down certain drugs commonly prescribed for heartburn or to inhibit the activity of blood platelets, which means that the drugs not enter their bloodstream in large enough doses to be effective. Genetics are also involved in diagnosing diseases passed down in the family. The "Ashkenazi mutation" in genes BRCA 1 and 2 is known to increase the risk of breast cancer by as much as 70 percent. Other genetic mutations have been found to be common in other population groups. Heart disease treatment can also benefit from genetic medicine. The Israel Heart Society has recommended since 2009 that people who have a relative who died young of a sudden heart attack undergo genetic testing. If they are found to be carriers of a certain mutation that increases the risk of an early heart attack, treatment is tailored for them to ensure a healthy lifestyle and proper medical follow-up. Genetics training is particularly important for family physicians, says Maya, because they are "responsible for the patient's connection to the entire medical network and they should know medical situations each of which is connected to a different specialist but is based on a genetic common denominator. The flood of articles on genetic connections to disease is also a reason to make sure physicians are better educated in this field. "Some doctors get enthusiastic over an article about a new gene and make decisions based on it, even if it's a small article from which no conclusions can be drawn," Maya says. "It is important to give doctors the tools to discern the information that is relevant to their field." The course at Beilinson will also include ethics. A candidate for inclusion in this year's "health basket" - the medications and technologies covered by HMOs - is a technology called PGD, or Preimplantation Genetic Diagnosis, which screens an embryo created by in-vitro fertilization for genetic defects to prevent passing them down to the next generation. This year it is proposed to include testing for one of the "Ashkenazi genes" that causes breast cancer as well as genes associated with Alzheimer's. "These are issues with ethical implications in terms of medical intervention in genetics and where to limit it," Maya says.
Zdroj: web
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‘BIGFOOT’ DNA SEQUENCED IN UPCOMING GENETICS STUDY
Five-Year Genome Study Yields Evidence of Homo sapiens/Unknown Hominin Hybrid Species in North America A team of scientists can verify that their 5-year long DNA study, currently under peer-review, confirms the existence of a novel hominin hybrid species, commonly called “Bigfoot” or “Sasquatch,” living in North America. Researchers’ extensive DNA sequencing suggests that the legendary Sasquatch is a human relative that arose approximately 15,000 years ago as a hybrid cross of modern Homo sapiens with an unknown primate species. The study was conducted by a team of experts in genetics, forensics, imaging and pathology, led by Dr. Melba S. Ketchum of Nacogdoches, TX. In response to recent interest in the study, Dr. Ketchum can confirm that her team has sequenced 3 complete Sasquatch nuclear genomes and determined the species is a human hybrid: “Our study has sequenced 20 whole mitochondrial genomes and utilized next generation sequencing to obtain 3 whole nuclear genomes from purported Sasquatch samples. The genome sequencing shows that Sasquatch mtDNA is identical to modern Homo sapiens, but Sasquatch nuDNA is a novel, unknown hominin related to Homo sapiens and other primate species. Our data indicate that the North American Sasquatch is a hybrid species, the result of males of an unknown hominin species crossing with female Homo sapiens. Hominins are members of the taxonomic grouping Hominini, which includes all members of the genus Homo. Genetic testing has already ruled out Homo neanderthalis and the Denisova hominin as contributors to Sasquatch mtDNA or nuDNA. “The male progenitor that contributed the unknown sequence to this hybrid is unique as its DNA is more distantly removed from humans than other recently discovered hominins like the Denisovan individual,” explains Ketchum. “Sasquatch nuclear DNA is incredibly novel and not at all what we had expected. While it has human nuclear DNA within its genome, there are also distinctly non-human, non-archaic hominin, and non-ape sequences. We describe it as a mosaic of human and novel non-human sequence. Further study is needed and is ongoing to better characterize and understand Sasquatch nuclear DNA.” Ketchum is a veterinarian whose professional experience includes 27 years of research in genetics, including forensics. Early in her career she also practiced veterinary medicine, and she has previously been published as a participant in mapping the equine genome. She began testing the DNA of purported Sasquatch hair samples 5 years ago. Ketchum calls on public officials and law enforcement to immediately recognize the Sasquatch as an indigenous people: “Genetically, the Sasquatch are a human hybrid with unambiguously modern human maternal ancestry. Government at all levels must recognize them as an indigenous people and immediately protect their human and Constitutional rights against those who would see in their physical and cultural differences a ‘license’ to hunt, trap, or kill them.” Full details of the study will be presented in the near future when the study manuscript publishes.
Zdroj: web
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Jews: A religious group, people or race?
As Diaspora Jews increasingly assimilate and intermarry with gentiles, and their Israeli counterparts marry Jews whose forebears came from the four corners of the earth, a window of opportunity to study Jewish genetics is gradually closing. In another generation or two, it may be possible only to know whether one bears a “Jewish genome” rather than identify the different genetic threads that once bound them together. For more than 100 years, both Jews and non-Jews have been trying to find out whether Jews are a religious group, a people or even a race. Some were motivated to use this information as a basis for discrimination or even murder, others to boast about supposed superior intellectual abilities and a disproportionately large number of Nobel Prize laureates. Jews with a family history of chronic or genetic diseases wanted to know if they were likely to contract them or pass them on to their children and grandchildren. The higher prevalence of Tay-Sachs, Gaucher and Canavan’s disease among Jews is well known, but some experts claim certain psychiatric, metabolic and oncological diseases are also more common among them. Now, Prof. Harry Ostrer has produced a 264-page, English-language volume melding together science, history and biography to better understand the complex subject. Titled Legacy: A Genetic History of the Jewish People, the $25 hardcover book was published by Oxford University Press. A Jewish medical geneticist at Yeshiva University’s Albert Einstein College of Medicine, Ostrer is also director of genetic and genomic laboratories at Montefiore Medical Center in New York. Almost two years ago, he was named to the Forward 50 list of “people who have made an imprint in the past year on the ways in which American Jews view the world and relate to each other.” A physics graduate of the Massachusetts Institute of Technology who received his MD from Columbia University College of Physicians and Surgeons, Ostrer trained in pediatrics and medical genetics at Johns Hopkins University and molecular genetics at the US National Institutes of Health. Before joining Einstein, he spent 21 years as professor of pediatrics, pathology and medicine and director of the human genetics program at New York University’s School of Medicine. While he has spent much of his career investigating the genetic basis for a variety of rare diseases from color vision deficiencies and thalassemia to sex development disorders – even going to the Far East to test Cambodian and Thai citizens for mutations that disrupt their blood – Ostrer has put a special emphasis on population genetics among Diaspora Jews, collaborating and competing with research groups in Israeli centers and others abroad. He co-established with Israeli-born Einstein researcher Dr. Gil Atzmon the Jewish HapMap Project on genomes of contemporary Jewish Diaspora groups (Hap refers to haplotype – a group of genes inherited together by an organism from a single parent). The book is divided into six large chapters – “Looking Jewish,” “Founders,” “Three Genealogies,” “Tribes,” “Traits and Identity” – plus 277 references. In the first chapter, he describes the work a century ago of Dr. Maurice Fishberg, a young Russian-Jewish immigrant physician in New York City, who “grappled with the issues of Jewish origins, identity and traits” in a series of articles that he made into a book: The Jews: A Study of Race and Environment. A one-time coal miner, the physician became chief medical examiner of new immigrants for United Hebrew Charities and then a physical anthropologist who confronted American supporters of restricting immigration who claimed the Jews brought in communicable diseases, especially tuberculosis. But his maps proved that the prevalence of TB was significantly lower in the lower Manhattan districts where Jewish immigrants congregated than in all other districts, apparently due to their better hygiene and eating habits due to kashrut. But he also found that “mental retardation, mental diseases...called hysteria and neurasthenia,” diabetes and “amaurotic family idiocy,” now known as Tay-Sachs disease, were more common among Jews, leading him to wonder about their heredity. Fishberg decided to become a physical anthropologist to measure and compare physical shapes such as head shape (using calipers) and pigmentation to scientifically determine “racial characteristics.” Researchers after him postulated that humans originated in Africa, and that over the millennia, their migration out of the continent led to genetic differentiation in which those with lighter skin, hair and eyes were more likely to survive in cooler climates and passed on their genes to produce new races. “Viewed in the context of Jewish history,” Ostrer wrote, “the genetic makeup of contemporary Jewish populations has been influenced by the geographic origins of a relatively small number of founders... Following the destruction of the Jewish kingdoms more than 2,000 years ago, the Jews became a migratory people who established communities throughout the world. Some of these communities retained their continuity over long periods of time. “Within those communities, Jews were linked by religion, customs, marriage and language. The designation ‘Jewish’ was limited by Jewish law to those whose mothers were Jewish. Entry [into] the community was possible through religious conversion, but this was not common. Jewish identity was maintained within these communities up to the present day.” Ostrer noted that Jews today can be designated according to where their forebears lived for many centuries as “Middle Eastern” (Mizrahi); Sephardi (originating in Spain and Portugal until the end of the 15th century); Ashkenazim, who moved from Italy and crossed the Alps and settled in the Rhineland and then other places in Europe; and North African Jews, who lived along the coast for over two millennia after being exiled after the destruction of the two Temples, mixed with surrounding populations. All this shaped the face of world Jewry. DR. CHAIM SHEBA, the pioneering Israeli geneticist who was surgeon-general of the Israel Defense Forces and Health Ministry director-general (after whom Sheba Medical Center at Tel Hashomer was named) is lauded in the book for his work to determine whether Jews constituted a single homogeneous group or a series of genetically related groups. He found that eating ful (fava beans) and certain anti-malaria medications can cause terrible anemias in certain people due to G6PD deficiency caused by genes that are found in certain non-Ashkenazi Jews, Greeks and African Americans. This led to Sheba becoming “the original force behind the concept of ‘Jewish genetic disease.’” The work of the past four decades has provided a basis for Sheba’s observations that “Jews from different Diaspora groups had different disease susceptibilities.” Other researchers identified the higher rate of Neimann-Pick, Canavan’s and Gaucher’s diseases among Jews of specific origins. Ostrer explained that in recent years, a method known as “coalescence,” that estimates when a mutation occurred in populations based on the observation that DNA is inherited in “blocks.” If people who have the same mutation share a large block, the mutation arose from a recent founder, but if the block is short, the founder lived long time ago. Thus this technique is similar to carbon dating for archeology. The author discusses the two breast/ovarian cancer mutations, BRCA1 and BRCA2, which do not cause most cases but are likelier in Ashkenazi Jews. He mentions that Rosalind Franklin, a young Orthodox Jewish scientist, discovered the structure of DNA with Watson and Crick in 1953, but unlike them, did not live to receive the Nobel Prize they did because she died at 37 of ovarian cancer caused by the mutant gene. Also mentioned is the University of Washington’s superb geneticist Prof. Mary-Claire King, who studies the genetics and interaction of genetics and environmental influences on human conditions such and is known for three major achievements – identifying the BRCA1 mutation, showing that humans and chimpanzees are 99 percent genetically identical; and applying genomic sequencing to identify victims of human rights abuses. King is a frequent visitor to Israel and collaborates regularly with Israeli scientists, including Sha’are Zedek Medical Center’s chief of medical genetics, Prof. Ephrat Levy-Lahad (whose work is also mentioned in the volume). The genetic link between members of the Jewish priestly tribe (Kohanim) through their paternally inherited Y chromosome, proven by geneticists Michael Hammer, Luca Cavalli-Sforza, Rambam Medical Center and Technion Prof. Karl Skorecki and others is described in detail as well. Ostrer said that his Jewish HapMap Project in New York City has so far shown “in exquisite detail what had been conjectured for a century. Jewish populations from the major Jewish Diaspora groups – Ashkenazi, Sephardic and Mizrahi – form a distinctive population cluster that is closely related to Semitic and European populations. Within this larger Jewish cluster, each of the Jewish populations formed its own subcluster.” A high degree of mixing of Ashkenazi, Sephardi, Italian and Syrian Jews caused them to become more closely related to each other than they were to Middle Eastern, Iraqi and Iranian Jews. This genetic split seemed to have occurred about 2,500 years ago. The author uses his observations to refute theories that Ashkenazi Jews are descendants of converted Khazars, a semi-nomadic people living in medieval Eurasia who welcomed Jews to their midst. He also reports that in addition to southern Europeans, the closest genetic neighbors to most Jewish groups were the Palestinians, Israeli Beduin and Druse. “The genetic clusters formed by each of these non-Jewish Middle Eastern groups reflects their own histories of marrying within the group,” he said. The issue of “Jewish intelligence” that seems to come up every time members of the “Chosen People” are awarded Nobel Prizes continues to be debated. There are those who contend there is a genetic basis for IQ and those who claim it comes from studiousness, from Torah learning and from the fact that Jews were held back by discrimination from joining the top ranks of the arts and sciences but rushed in after emancipation. “Breeding, selection and education may all have contributed to Jewish intellectual accomplishment, but so, too, did being in the right place at the right time,” and showing that they were worthy of emancipation by excelling. The belief that Jews constitute a religious, rather than ethnic or racial group in the US and other Western countries is widespread. “Jewish” was never a category for race in the US Census, Ostrer notes, even though genetic studies “would seem to refute this... Jewishness at a genetic level can be characterized as a tapestry with the threads represented as shared segments of DNA and no single thread required for composition of the tapestry,” he writes. Genetic analysis of Jews have high stakes, since being Jewish not only decides who belongs to the family and can take part in Jewish life and earn Israeli citizenship but also “touches on the heart of Zionist claims for a Jewish homeland in Israel.” Ostrer concludes his fascinating book by saying that much about Jewish genetics remains unknown but will probably be discovered in the next few decades as more is learned about susceptibility to diseases, origins and genetics of positive traits. “With Jews and non-Jews alike wanting to know about their origins, ancestors and relatives, it will take its place in the formation of group identity alongside shared spirituality, shared social values and a shared cultural legacy.”
Zdroj: web
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Cheap DNA Sequencing: What's in it for You?
Your DNA can reveal more about your body — and what the future has in
store for it — than a stethoscope and a tongue depressor ever could.
Thanks to the Human Genome Project, which identified all the genes in
the human DNA, scientists better understand how our biological makeup
affects our health. This milestone kick-started the commercialization of
DNA sequencing, which refers to determining the exact order of the
bases in a strand of DNA. Five years from now, the process may be as
simple as picking up a kit at your local pharmacy, similar to a
pregnancy test.
"It's just a question of time," says Daniel MacArthur, a genomics
researcher at Massachusetts General Hospital. "Right now it's just way
too expensive. But that will change fast."
When commercialization eventually drives down the price, DNA
sequencing could even be a project your kids do in science class,
MacArthur suggests.
DNA sequencing may sound like a cool plot line from a sci-fi thriller, but the question really is, what's in it for you?
Your DNA, in Recreational Mode
One of the most common uses for DNA sequencing today is to determine
predispositions for genetic diseases or complications. But there are
also more "recreational" aspects of genomics.
Genetic testing can be used to track down distant members of your
family tree by looking for shared segments of DNA. Additionally, you can
learn more about your ancestry by looking for genetic clues to where
your deeper ancestors lived. For instance, you may be able to determine
whether you have any detectable Native American ancestry.
23andMe , a
personal genome service, sells a DNA Spit Kit — users simply spit in a
tube and send it to a lab for testing. For $299, researchers will
analyze your DNA for information about your ancestry and health. From
there, you can access a database of more than 200 health and trait
reports or sift through the world's largest DNA database to find
connections you never knew.
When it comes to your health, DNA sequencing can tell you things
beyond disease susceptibility — like whether you sneeze in sunlight, or
whether you can really smell asparagus in your urine. Is that
information really helpful in the long run? Maybe not. Nonetheless,
we're continually fascinated by our human ticks.
"For some people, these non-medical aspects end up proving much more
interesting than their disease predictions," says MacArthur. "But this
isn't just for fun — for people who already have serious diseases, DNA
sequencing can profoundly change their diagnosis and treatment."
A Cure for Rare Diseases? Thanks, Crowdfunding
Four-year-old
Maya suffers from global developmental delays. Despite visits to
several physicians, her condition remained a mystery for years. Doctors
knew it was genetic, but no tests turned up a concrete explanation.
Last spring, Maya connected with Rare Genomics Institute (RGI), a service that helps families design research studies and raises money online via a Kickstarter-like crowdfunding platform to pay for DNA sequencing for children with rare genetic disorders.
Maya's fundraising took just six hours.
One year and a lengthy research process later, researchers called RGI
with a potential breakthrough: They found a new gene error.
"Maya is the first person in history with an error in this gene,"
says RGI founder Jimmy Lin. "So, you could say we may have identified a
new disease through this ... and we're now able to take next steps."
DNA sequencing has already revolutionized the way we diagnose and
treat diseases like cancer. However, it's especially useful for rare
diseases that may hinge on just a few individuals.
But while the process could potentially open the door to a cure for a
rare disease, this is where DNA sequencing falls into a financial gap —
there are no advocacy groups for unknown diseases. Additionally, health
insurance usually won't pick up the tab for this type of service.
"Researchers don't tend to study individual people," says Lin, who
started RGI to fill that void into which children with rare diseases
fall. "Often, these children present anatomical problems, like displaced
hearts," Lin explains. "Or delays in development, like talking."
Although the company is just a little older than one year, it already
has about 20 cases on deck. On average, each case costs $7,500, all of
which is raised through crowdfunding.
Can Insurance Companies Use Your DNA Against You?
DNA sequencing doesn't come without its share of fine print.
"There are no fundamental barriers to cheap, widely available DNA
sequencing," MacArthur says. "It's just a question of how society will
adapt to that technology. That, I think, is much less clear. People tend
to get panicky about invasion of genetic privacy."
It's hard to say how America's healthcare system will be structured
10 years from now. But if it's similar to how it functions today,
skyrocketing premiums could be a real issue when it comes to
standardizing genetic testing.
Insurance companies may be able to use your genetic information when
assessing certain parts of your coverage. In 2008, Congress passed a law
that should, theoretically, protect us from such manhandling. The
Genetic Information Nondiscrimination Act (GINA) prohibits insurance
companies from using genetic information to determine coverage costs.
But there are a lot of holes. For example, GINA doesn't cover life
insurance or long-term care. In cases like these, genetic information
could be used to calculate costs or type of coverage available to that
individual.
"The key is that there has to be a safety net for people with these serious genetic diseases," says MacArthur.
On the other hand, DNA sequencing could swing in a positive direction
— for a healthy person, that is. A genetics report free of disease risk
could mean coverage cost cuts, similar to how an auto insurance company
might give a discount to a safe driver.
Expect DNA sequencing to be a routine procedure in hospitals in 5 to
10 years. In the short term, this process will be used to test and
diagnose symptoms that the patient is already experiencing. But if
researchers meet their goals, DNA sequencing may be as routine as a
checkup in your family doctor's office.
Zdroj: web
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Pre-Natal Genetic Testing Breakthrough: "Who Deserves to Be Born"
The New York Times is
reporting on its front page a new scientific
breakthrough in which a non-invasive technique can be used to
sequence nearly the entire genome of a fetus. Basically, the team
of researchers led by Jay Shendure at the University of Washington
can find the entire complement of a fetus' genes floating around in
the bloodstream of the woman who is bearing it. The Times
reports:
The accomplishment heralds an era in which parents might find it
easier to know the complete DNA blueprint of a child months before
it is born.
That would allow thousands of genetic diseases to be detected
prenatally. But the ability to know so much about an unborn child
is likely to raise serious ethical considerations as well. It could
increase abortions for reasons that have little to do with medical
issues and more to do with parental preferences for traits in
children.
That's right - the Times jumps immediately to
highlighting the uses of a new technology - potential parental
preferences for non-disease traits - that might provoke opposition
to it based people's natural preferences for the status quo. And
what's an article without a portentous quote from some bioethicist
about how fraught with moral issues the new technology is. In this
case, left-wing bioluddite Marcy Darnovsky obliges:
“There are some scenarios that are extremely troubling,” said
Marcy Darnovsky, associate executive director of the Center for
Genetics and Society, a public interest group in Berkeley, Calif.
The tests will spur questions on “who deserves to be born,” she
said.
This new breakthrough clearly implicates the abortion debate and
the question of when a person becomes a person. H&R readers and
commenters: let's just stipulate what we each believe about that
and contemplate the odd notion of "deserves to be born."
Nobody "deserves" to be born. The advent of each one of us is
entirely contingent on decisions made by our parents (and their
parents and then their parents and so on down to the origin of life
and the Big Bang) over which we had absolutely no say. For example,
I marvel at the fact that my parents met at a New Year's party in
1953, got married two months later, and then I was born on November
23. Had they delayed their wedding one week, I would never have
existed. New technologies associated with reproduction just add
more contigencies to the birth of any specific individual. Of
course, once born, people deserve to be treated morally by
others.
In the future when the technology is perfected and much cheaper,
should would-be parents be allowed to take advantage of it? Yes, I
argue in my 2001 column, Sex
Selection , where I explained:
So should parents be permitted to select traits other than the
sex of their children? Few aspects of human development are more
significant than one's sex; it's a central fact of one's identity
as a human being. If it is ethically permissible for parents to
make that choice, the case for letting them make less significant
genetic choices for their offspring is already made. (Keep in mind
that we are not talking about directly manipulating the genetic
makeup of any individual. We're talking about permitting parents to
test and choose among embryos for those traits they believe will
give their children their best chances in life.)
Australian bioethicist Julian Savulescu is right when he reminds
us, "The Nazis sought to interfere directly in people's
reproductive decisions (by forcing them to be sterilized) to
promote social ideals, particularly around racial superiority. Not
offering selection for nondisease genes would indirectly interfere
(by denying choice) to promote social ideals such as equality or
'population welfare.' There is no relevant difference between
direct and indirect eugenics. The lesson we learned from eugenics
is that society should be loath to interfere (directly and
indirectly) in reproductive decisionmaking."
Zdroj: web
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DNA Blueprint for Fetus Built Using Tests of Parents
For the first time, researchers have determined virtually the entire
genome of a fetus using only a blood sample from the pregnant woman and a
saliva specimen from the father.
The accomplishment heralds an era in which parents might find it easier
to know the complete DNA blueprint of a child months before it is born.
That would allow thousands of genetic diseases to be detected
prenatally. But the ability to know so much about an unborn child is
likely to raise serious ethical considerations as well. It could
increase abortions for reasons that have little to do with medical
issues and more to do with parental preferences for traits in children.
“It’s an extraordinary piece of technology, really quite remarkable,” said Peter Benn, professor of genetics
and developmental biology at the University of Connecticut, who was not
involved in the work. “What I see in this paper is a glance into the
future.”
The paper, published Wednesday in the journal Science Translational Medicine, was written by genome scientists at the University of Washington .
They took advantage of new high-speed DNA sequencing and some
statistical and computational acrobatics to deduce the DNA sequence of
the fetus with about 98 percent accuracy.
The process is not practical, affordable or accurate enough for use now,
experts said. The University of Washington researchers estimated that
it would cost $20,000 to $50,000 to do one fetal genome today.
But the cost of DNA sequencing is falling at a blistering pace, and
accuracy is improving as well. The researchers estimated that the
procedure could be widely available in three to five years. Others said
it would take somewhat longer.
It is already possible to determine the DNA sequence of a fetus by acquiring fetal cells through amniocentesis or chorionic villus sampling , which involves testing the placental tissue. But these procedures are invasive and carry a slight risk of inducing a miscarriage .
For couples worried about passing on a genetic disease, it is also
possible to use in vitro fertilization and have an embryo genetically
tested before implantation into the womb.
But the technique described in the paper would not require complete
cells from the fetus and would make such DNA testing easier and less
risky.
“If this sort of thing is ever to be used on a widespread basis, I think
it necessarily has to be noninvasive,” said Jay Shendure, associate
professor of genome sciences at the University of Washington, who
supervised the research team.
The genome was determined from blood samples taken 18.5 weeks into the pregnancy ,
although the researchers said the technique could probably be applied
in the first trimester, as early as or even earlier than some invasive
techniques.
The technique takes advantage of the discovery in the 1990s that
fragments of DNA from the fetus can be found in a pregnant woman’s blood
plasma, probably the result of fetal cells dying and breaking apart.
These fragments can be genetically analyzed, providing that the fetal
DNA fragments can be distinguished from the far more numerous fragments
that come from the mother herself.
The analysis of fetal DNA fragments found in a pregnant woman’s blood is
already used in new commercially available tests of the fetus’s gender,
its paternity and whether it has Down syndrome . But reconstructing an entire genome from DNA fragments is much more difficult.
Such information would allow detection of so-called Mendelian disorders, like cystic fibrosis , Tay-Sachs disease and Marfan syndrome , which are caused by mutations in a single gene.
More than 3,000 such diseases collectively occur in about 1 percent of
births. The mutations can be inherited from the parents or they can
arise spontaneously in the fetus.
Researchers led by Dennis Lo at the Chinese University of Hong Kong
first showed in 2010 that reconstructing a fetal genome would be
possible. Other work toward this goal has been done by Stephen Quake and
colleagues at Stanford University.
But Dr. Lo’s team used a maternal sample obtained invasively. And it
could determine only the inherited mutations, not the spontaneous ones.
The University of Washington researchers, using an approach partly
developed by a graduate student, Jacob O. Kitzman, did not need an
invasive test. And they were able to detect 39 of 44 such spontaneous
mutations, though with a huge number of false positives.
“This will be a step toward having a better and better prenatal diagnosis
that detects more and more at a reliable cost,” said Dr. Arthur L.
Beaudet, chairman of molecular and human genetics at Baylor College of
Medicine in Houston.
Dr. Beaudet, who was not involved in the work, said that spontaneous mutations account for about 10 percent of cases of mental retardation and other learning disabilities.
The ability to sequence an entire fetal genome is likely to raise
numerous issues. “There are some scenarios that are extremely
troubling,” said Marcy Darnovsky, associate executive director of the
Center for Genetics and Society, a public interest group in Berkeley,
Calif. The tests will spur questions on “who deserves to be born,” she
said.
Use of the approach could lead to an increase in abortions because some
parents might terminate the pregnancy if the fetus was found to have a
genetic disease. But it is also possible that parents may be tempted to
terminate if the fetus lacked a favorable trait like athletic prowess.
“You could start doing things more toward the direction of positive
selection,” said Dr. Stephen A. Brown, associate professor of obstetrics
and gynecology at the University of Vermont.
Moreover, a full fetal genome sequence would turn up numerous mutations
for which information is lacking as to whether they cause disease,
posing a dilemma for expectant parents and their doctors.
“Our capacity to generate data is outstripping our ability to interpret
it in ways that are useful to physicians and patients,” the University
of Washington researchers wrote their paper. “That is, although the
noninvasive prediction of a fetal genome may be technically feasible,
its interpretation — even for known Mendelian disorders — will remain a
major challenge.”
The researchers sequenced the genomes of the mother and father. They
then sequenced nearly three billion DNA fragments from the mother’s
blood. The samples, obtained from a tissue bank, were from unknown
donors.
Since people have two copies of each chromosome, they have two versions
of each gene. Only one version is passed to the baby.
Determining which version at any given spot in the father’s genome was
passed to the fetus was fairly straightforward, since any fragments of
DNA in the mother’s blood containing a sequence unique to the father had
to have come from the fetus.
Determining which of two variants at a given location — call them A and B
— the fetus inherited from the mother was more difficult. If the fetus
inherited version A, then fragments containing A (which could come from
either the fetus or the mother) would outnumber fragments containing B
(which could come only from the mother). But since there are relatively
few fetal fragments, the difference would be small and hard to detect.
The researchers used an approach they developed to figure out which
variations in the mother’s genome were likely to be passed to the baby
together. That made the problem more tractable than trying to make a
call individually at three million locations in the genome.
After it was determined what the fetus inherited from the mother and
father, what was left in the fetus’s DNA was considered a possible
spontaneous mutation. There were initially 25 million such candidates,
though statistical approaches narrowed that to 3,800. That still vastly
exceeded the 44 such spontaneous mutations found after the baby was born
and its cord blood sequenced. Having so many false positive findings of spontaneous mutations could worry parents and doctors.
“There’s definitely plenty of room for improvement,” Professor Shendure said. But, he added, “This is not science fiction anymore.”
Zdroj: The New York Times
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New Genetic Method Developed to Pinpoint Individuals' Geographic Origin
Understanding the genetic diversity within and between populations has important implications for studies of human disease and evolution. This includes identifying associations between genetic variants and disease, detecting genomic regions that have undergone positive selection and highlighting interesting aspects of human population history. Now, a team of researchers from the UCLA Henry Samueli School of Engineering and Applied Science, UCLA's Department of Ecology and Evolutionary Biology and Israel's Tel Aviv University has developed an innovative approach to the study of genetic diversity called spatial ancestry analysis (SPA), which allows for the modeling of genetic variation in two- or three-dimensional space. Their study is published online this week in the journal Nature Genetics. With SPA, researchers can model the spatial distribution of each genetic variant by assigning a genetic variant's frequency as a continuous function in geographic space. By doing this, they show that the explicit modeling of the genetic variant frequency -- the proportion of individuals who carry a specific variant -- allows individuals to be localized on a world map on the basis of their genetic information alone. "If we know from where each individual in our study originated, what we observe is that some variation is more common in one part of the world and less common in another part of the world," said Eleazar Eskin, an associate professor of computer science at UCLA Engineering. "How common these variants are in a specific location changes gradually as the location changes. "In this study, we think of the frequency of variation as being defined by a specific location. This gives us a different way to think about populations, which are usually thought of as being discrete. Instead, we think about the variant frequencies changing in different locations. If you think about a person's ancestry, it is no longer about being from a specific population -- but instead, each person's ancestry is defined by the location they're from. Now ancestry is a continuum." The team reports the development of a simple probabilistic model for the spatial structure of genetic variation, with which they model how the frequency of each genetic variant changes as a function of the location of the individual in geographic space (where the gene frequency is actually a function of the x and y coordinates of an individual on a map). "If the location of an individual is unknown, our model can actually infer geographic origins for each individual using only their genetic data with surprising accuracy," said Wen-Yun Yang, a UCLA computer science graduate student. "The model makes it possible to infer the geographic ancestry of an individual's parents, even if those parents differ in ancestry. Existing approaches falter when it comes to this task," said UCLA's John Novembre, an assistant professor in the department of ecology and evolution. SPA is also able to model genetic variation on a globe. "We are able to also show how to predict the spatial structure of worldwide populations," said Eskin, who also holds a joint appointment in the department of human genetics at the David Geffen School of Medicine at UCLA. "In just taking genetic information from populations from all over the world, we're able to reconstruct the topology of the global populations only from their genetic information." Using the framework, SPA can also identify loci showing extreme patterns of spatial differentiation. "These dramatic changes in the frequency of the variants potentially could be due to natural selection," Eskin said. "It could be that something in the environment is different in different locations. Let's say a mutation arose that has some advantageous property in a certain environment. So you can imagine then that a kind of force for genetic selection would make this mutation more common in that environment." The research team began to examine all of the genes, and for each gene they computed how sharp of a change there was in the frequencies. They soon discovered that the genes which had the largest and most extreme changes are the ones that are known to have experienced selection in the recent past. "So this is a new method for finding genes that are also undergoing selection in humans," Yang said.
Zdroj: web
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'Good' Cholesterol May Not Be That Good
Individuals born with a genetic predisposition toward high plasma
high-density lipoprotein (HDL) cholesterol levels do not have a lower
risk of myocardial infarction, calling into question whether HDL
cholesterol is causally related to cardiovascular risk, researchers
found.
In a mendelian randomization analysis, individuals carrying a
single nucleotide polymorphism (SNP) associated exclusively with higher
plasma HDL cholesterol had higher levels of the lipid, but a myocardial
infarction (MI) risk similar to that of other individuals (OR 0.99, 95%
CI 0.88 to 1.11, P =0.85), according to Sekar Kathiresan, MD, of Massachusetts General Hospital in Boston, and colleagues.
On the other hand, a collection of SNPs related to higher low-density
lipoprotein (LDL) cholesterol levels was associated with an increased
risk of MI, as expected (OR 2.13, 95% CI 1.69 to 2.69), the researchers
reported online in The Lancet .
"These data challenge the concept that raising of plasma HDL
cholesterol will uniformly translate into reductions in risk of
myocardial infarction," they wrote.
In addition, "these findings emphasize the potential limitation of
plasma HDL cholesterol as a surrogate measure for risk of myocardial
infarction in intervention trials."
Observational studies have shown a relationship between higher HDL
cholesterol levels and a lower risk of MI, but it remains unclear
whether the relationship is causal. Agents aimed at increasing HDL
cholesterol levels have not been shown to reduce cardiovascular risk in
randomized trials.
Kathiresan and colleagues first evaluated the effect of a SNP in the endothelial lipase gene (LIPG Asn396Ser) , which is related to higher HDL cholesterol levels. About 2.6% of individuals carry the allele.
Among four prospective cohort studies, carriers of the allele had HDL
cholesterol levels that were higher, on average, by 0.14 mmol/L (5.4
mg/dL).
That difference would be expected to decrease the risk of MI by a
relative 13% (OR 0.87, 95% CI 0.84 to 0.91), if the relationship between
HDL cholesterol and MI risk were causal. But the allele was not
associated with risk of MI among six prospective cohort studies and 14
case-control studies that included 20,913 patients with MI and 95,407
controls.
A genetic score consisting of 14 SNPs exclusively associated with HDL
cholesterol was not associated with MI risk either (OR 0.93, 95% CI
0.68 to 1.26).
The authors acknowledged the inherent limitations to mendelian randomization, including the absence of an association of individual SNPs with MI because of low statistical power.
In an accompanying editorial, Steve Humphries, PhD, of
University College London, and colleagues noted that the study is
consistent with previous mendelian randomization analyses focused on the
same issue and adds to an increasing number of mendelian randomization
studies of coronary heart disease biomarkers.
"As the research area matures, a consensus for methodology and
reporting will be important, particularly when the potentially powerful,
but also complex, genetic risk score approach is used," they wrote.
"Taken together with adequately powered studies, mendelian
randomization is likely to yield insights that can both guide public
health policy and prioritize potential therapeutic targets."
Zdroj: web
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Genetic Testing in Gastrointestinal Cancers: A Case-Based Approach
ABSTRACT: High-risk genetic mutations that predispose individuals
to various gastrointestinal (GI) cancers account for only about 5% of
the population burden of these diseases. However, because early
identification of at-risk individuals can so dramatically affect primary
disease prevention, it is imperative that families who harbor
susceptibility to these cancers be identified. The benefits of
determining an underlying genetic susceptibility are important both for
an individual patient’s ongoing management and for his or her family,
where early identification of at-risk persons, along with the adoption
of frequent cancer screenings and/or prophylactic risk-reduction
surgeries, can have dramatic lifeprolonging benefits. In this article,
we use a case-based approach to focus on the hereditary aspects of the
most common GI cancers, including pancreatic, gastric, and colon cancer.
Indicators
that identify individuals who may harbor germline mutations
predisposing them to cancer include a family history of multiple cancers
that reflect a pattern of disease, young age at onset, multiple primary
tumors, tumors with particular histologic phenotypes, the presence of
precursor lesions, and other related manifestations that cosegregate
with cancer in the family. For individuals identified as being at risk
for a cancer predisposition syndrome, referral to a genetic counselor
for genetic risk assessment and testing is necessary and helps to ensure
a comprehensive genetic evaluation. The investigation of a family for
an underlying genetic cancer predisposition is guided by specific
questions, including the type and age of cancer diagnoses in the family;
whether there is access to pathology reports confirming the site of
cancer and indicating histologic subtype; and in the scenario where the
patient is unaffected, whether there is access to blood, tissue, or
stored DNA from an affected family member on which genetic testing can
be performed.
Typically,
genetic testing should begin with the individual in the family most
likely to be affected with the cancer predisposition syndrome, ie, with
the family member who has the most severe disease, earliest onset, or
rarest phenotype. Testing this individual decreases the likelihood of
testing a family member with a phenocopy (eg, colon cancer that occurred
sporadically) and is typically the most informative approach.
Familial
clustering, evident in many cancer types, can in part be attributed to
shared environmental exposures as well as to genetic susceptibility
conferred by low-, medium-, or high-risk inherited factors. The
heritable component of disease can be measured through studies comparing
rates of disease in monozygotic vs dizygotic twins. In the case of
cancer, an increased heritability has been shown for a variety of
cancers, including prostate, colorectal, and breast cancers.[1] Further
evidence for increased heritability can be ascertained from
epidemiologic studies using cancer data from homogenous populations that
show greater than expected observed rates of certain types of cancer
within families.[2] In the case of families with multiple affected
individuals in subsequent generations, there is heightened suspicion for
rare mutations in genes that confer a high risk of cancer. In families
where the pattern is not as striking, the cancer predisposition may
still be genetic in origin but could be due to lower-penetrance risk
variants. Genome-wide association studies have uncovered common risk
variants in the genome that confer susceptibility to certain types of
cancer[3]; however, independently, each of these low-risk variants only
marginally increases a person’s risk of cancer above that of the general
population. Multiplicative models of common risk variants could
potentially explain a proportion of familial clustering or be used to
modify risk within moderate- to high-risk pedigrees, but as of yet, the
clinical utility of redefining risk based on common variation has not
been demonstrated.
To date, a large portion of the genetic etiology of hereditary cancer
predisposition remains unexplained; even many seemingly high-risk
families will not have an identifiable mutation in known cancer
predisposition genes. However, with current technological advances in
sequencing, rather than testing an individual for a specific gene or
genes, clinical genetic testing may eventually evolve to incorporate
whole-exome or whole-genome testing, in which all genes are assessed and
the culprit genetic changes are identified after testing.
Theoretically, this could reveal high-, medium-, and low-risk factors
that might contribute to a familial cancer in an individual. In
addition, factors such as genetic background and epigenetics (changes
not encoded in the genome, resulting instead from environmental
exposures that influence gene expression) may also further influence
disease penetrance and affect an individual’s cancer risk.
To
illustrate the benefits of genetic testing in individuals with a
hereditary predisposition to GI cancers, we have provided four scenarios
that are typical of what is encountered in the clinic. For each case,
the general considerations outlined in Table 1 should be taken into account during the genetic risk assessment process.
Case: Mr. X is a 58-year-old man with a recent
diagnosis of metastatic pancreatic cancer. On review of family history,
you find a history of pancreatic, breast, and prostate cancers on the
maternal side of the family (Figure 1 ).
There is no personal or family history of melanoma, and on examination
of his skin you do not find perioral freckling, melanomatous lesions, or
evidence of old skin surgeries.
Based on the recently updated
National Comprehensive Cancer Network (NCCN) guidelines,[4] hereditary
breast ovarian cancer (HBOC) syndrome should be considered in
individuals with pancreatic adenocarcinoma diagnosed at any age who have
two or more close relatives with breast and/or ovarian and/or
pancreatic cancer diagnosed at any age. Thus, after a discussion with
the patient regarding the potential usefulness to him and his family
members of identifying an inherited mutation, you refer the patient to
clinical genetics for further discussion of genetic testing.
Genetic evaluation: A total of 43,920 new diagnoses of pancreatic
cancer in US men and women is projected for 2012.[5] A quarter of these
will prove to be secondary to environmental factors such as smoking;
however, roughly 4,392 individuals (10%) will prove to have familial
clustering of the disease, with 2% having disease resulting from a
mutation in a high-risk Mendelian susceptibility gene (Figure 2 ).
In view of Mr. X’s family history of pancreatic, breast, and prostate cancers, HBOC syndrome is considered. The BRCA2
cancer susceptibility gene has been shown to be associated with
sporadic and familial pancreatic cancer,[6,7] with the Breast Cancer
Linkage Consortium study and other studies observing a 3.5- to 7-fold
increased risk of pancreatic cancer in families carrying a BRCA2 mutation.[8,9] In patients with familial pancreatic cancer, a BRCA2 mutation is identified in 11% to 17% of families.[7,10] The association between BRCA1 mutations and pancreatic cancer is not as well defined, but the relative risk of pancreatic cancer in BRCA1 mutation carriers has been estimated to be two-fold higher than in the general population.[11]
It is notable that mutations in the BRCA1/2
genes, while rare in the general population, are more prevalent in
certain ethnic groups, such as Ashkenazi Jews. Since Mr. X is of
Ashkenazi Jewish ancestry, testing begins with evaluation for the three
Ashkenazi founder mutations, which account for ~90% to 95% of BRCA mutations in the Ashkenazim. Genetic testing reveals the presence of the BRCA2
6174delT germline mutation, the most common Ashkenazi founder
mutation.[12] In patients of Ashkenazi ancestry (unselected for family
history) with resected pancreatic cancer, 5.5% were found to harbor a BRCA founder mutation, and in Ashkenazi breast-pancreas families, 14.2% were BRCA mutation–positive, with nearly equal distribution of BRCA1 and BRCA2 mutation carriers, suggesting that both of these genes may be involved with pancreatic cancer risk.[13,14]
During
the genetic assessment of patients with pancreatic cancer, a number of
other hereditary pancreatic cancer predispositions may also be
considered (Figure 2). Peutz-Jeghers syndrome,[15] which has a relative
risk of 132 for pancreatic cancer,[16] is usually associated with a
history of intestinal polyposis and often presents with intussusception,
gastrointestinal bleeding, and/or perioral freckling. Familial
adenomatous polyposis, which has a relative risk of 4.5 for pancreatic
cancer,[17] is associated with a history of colorectal polyps or
colorectal cancer; extraintestinal features such as congenital
hypertrophy of the retinal pigment epithelium; or extracolonic tumors,
such as pediatric hepatoblastomas, sebaceous adenomas, osteomas,
desmoids, or medulloblastomas. Lynch syndrome has a ~9-fold increase in
risk for pancreatic cancer above that of the general population[18]; a
history of colorectal, endometrial, and other cancers can also usually
be found. Familial atypical multiple mole melanoma (FAMMM) syndrome,
associated with germline mutations in CDKN2A , has a relative risk
of 13 to 22 for pancreatic cancer, and is generally associated with a
history of melanomas or dysplastic nevi.[19] In addition, PALB2
mutations, thought to be associated with both breast and pancreatic
cancer susceptibility, may also be considered.[20-22] Furthermore, other
very rare conditions can be associated with an increased risk of
pancreatic cancer, including hereditary pancreatitis, which has a
relative risk of 53 to 87 for pancreatic cancer (Table).[23-25]
In terms of oncologic treatment, identification of a BRCA
mutation in a patient with pancreatic cancer is becoming increasingly
important, since new therapies, such as poly(ADP-ribose) polymerase
(PARP) inhibitors, have shown significant activity in patients with
advanced BRCA -associated breast and ovarian cancers and hold potential for the treatment of BRCA -associated pancreatic cancer as well.[26] In fact, clinical trials exploring the efficacy of PARP inhibitors in BRCA -associated pancreatic cancer are currently underway.
With the knowledge that a BRCA
mutation has been identified in this patient, cascade testing of family
members can be performed so that at-risk family members can undertake
the recommended cancer screening and prevention strategies outlined in Table 2 .
Although pancreatic cancer screening studies to date have not
demonstrated a decrease in pancreatic cancer mortality, participation in
clinical trials assessing the efficacy of pancreatic cancer screening
in high-risk individuals may be a consideration for some BRCA -positive families with a history of pancreatic cancer.
.......
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Do Genes Really Augur Your Future?
For some people, genes are key to predicting our future health. For
others, genes as crystal balls are overhyped. Let's call it a truce
because
both sides are right.
Recently, two headlines announced important news about the impact of
genes in assessing and predicting future health. These came from the
New York Times , but could have been from any number of other media outlets that carried the stories:
Scientists Link Gene Mutation to Autism Risk Study Says DNA's Power to Predict Illness Is Limited
The casual reader might be excused if they took away the idea
that scientists had on the one hand discovered a rogue gene responsible
for autism, and
on the other had found that DNA isn't very helpful in predicting
disease. These readers might also be forgiven if they wondered how
these two findings
could each be true.
In fact, both headlines are correct - though not entirely. This
is because geneticists over the years have identified a slew of gene
markers linked to
disease, some of which have turned out, upon further research,
to be useful for predicting and understanding disease. Others are not
because most of
what happens to the majority of us genetically is far more
complex and nuanced.
Yet genetics in the public forum is often a discussion of
oversimplification and extremes. Some scientists, entrepreneurs, and
journalists portray
genes and gene markers as near-magical fortune-tellers about a
person's health future. Others claim that the first group has overhyped
genetics and
underplayed the role of the environment and other factors that
also impact disease.
The "mighty gene" storyline has its roots in the late 1980s and
1990s effort to sequence the human genome. Boosters in science and
industry elevated
genes to superstar status in part because they genuinely
believed that DNA was the key driver in even common diseases. This also
helped to sell a Human
Genome Project that required billions of dollars from the U.S.
Congress - and billions more from investors to sequence DNA and to
hopefully turn this
knowledge into drugs and other treatments.
Fifteen years ago the Genes-'R-Everything fervor was so
convincing that it attracted the tech-dystopia police - those thinkers
and artists who are
always looking for worst-case scenarios of technology run amok.
In this case, the prospect of a world where genes truly were paramount
led to movies
like Gattaca , which in 1997 depicted a world where one's DNA determined everything from lovers to
jobs - and about one man's effort to overcome his genetic deficits.
Thankfully, Gattaca's assumptions about the
deterministic power of genes was wrong, although the director and
screenwriter Andrew Niccol can
be pardoned if he believed the hyperventilated talk at the time
about the potential power of genes to not only diagnose and treat
disease, but to
predict a person's bio-future.
The appearance of Gattaca and other deterministic
discourse brought forth cries of "DNA hype" by the time the human genome
was fully sequenced
in 2003. This crescendoed in late 2007 when the first direct to
consumer genetic testing companies, 23andme and deCodeme, appeared with
products that
claimed to offer customers predictive risk factors for future
disease, along with probabilities for having other traits like curly
hair.
Many geneticists - some of them the same ones who lauded the
future of genetics in the 1990s - decried the commercialization of
genetics as promising
too much.
Yet like many myths, the debate over what genes really do dates
back to time even before the nineties, to 1953 and the discovery by
James Watson and
Francis Crick (with a major assist from Rosalind Franklin) that
DNA is a double helix.
Crick added to the cult of the super-gene in the 1960s with his
notion of a "Central Dogma" in genomics - the idea that one gene equaled
the production
of one protein (proteins are what genes are coded to make in a
cell) which equaled one disease or trait - the point being that genes
were the key.
Few people know, however, that Crick's "Central Dogma" was a
joke. A man who loved to poke fun, Crick was also a vociferous atheist
who disliked dogmas
of all kinds - including those in science. He created the
Central Dogma as a humorous reaction to people that believed that genes
were everything,
which most scientists even then knew was an oversimplification. (For
more on this history check out my book, Masterminds: Genius, DNA, and the Quest to Rewrite Life ).
And yet, to add to the complexity inherent in genetics, the
central dogma in some cases is true. For instance, there are rare
genetic mutations -
glitches in critical sequences of DNA - that are directly
responsible for diseases such as Down syndrome and Tay-Sachs. For these
terrible and usually
fatal conditions, single mutations are highly predictive.
For most common diseases, however, this has not turned out to be
the case. The impact of single genetic mutations in auguring risk
factors for, say,
diabetes and many cancers, is at best only slightly more
informative than knowing one's average risk for these maladies.
This is the point of the study published last week in Science Translational Medicine, which
looked at the predictive power of genes for 24 common diseases.
Researchers at Johns Hopkins studied the
genetics and the outcomes of over 53,000 twins born with
identical DNA. They discovered that for 20 major diseases the genes had
little or no extra
predictive power.
This is what the headline above reports, which seems like a
victory for the "genes are overhyped" camp. Yet the news here is also
more nuanced. It
turns out that for the four other diseases analyzed by the Hopkins team -
Alzheimer's disease , autoimmune
thyroid disease, Type 1 diabetes and
heart disease for men - genetic tests can identify up to 75 percent of those who will get these diseases.
Neither does the headline above about new gene mutations for autism tell the whole story about that discovery. As the Times
story under the
headline explains, the newly identified mutations - made by
three different teams at Yale, Harvard and at the University of
Washington in Seattle and
reported in Nature -
are extremely rare, impacting only a handful of patients. Nor do they
seem to have much
relevance to diagnosing, treating, or predicting autism, though
the researchers believe the discoveries could be important for better
understanding
mechanisms of the disease.
While I was writing my recent book, Experimental Man ,
and after its publication, scientists identified over 23,000 personal
genetic risk factors for me - everything from a low risk of having brown
eyes (true: my eyes are blue) to a high risk
for Parkinson's disease (false: at age 54 I thankfully do not
have any sign of this condition). Other risk factors suggest a high
probability that I
will suffer side effects from certain drugs, such as statins,
which I will keep in mind should my cholesterol soar.
Otherwise, my vast library of possible genetic futures has not
changed my life - in part because I'm not sure what to believe given the
current
dialectic of genes as vital predictors to some and as overblown
to others. I expect this to change as interpretations of personal
genetic traits
improve, but this remains in the future.
Nor does it make sense to emphasize the augurs for the future in
our DNA when they are just part of the equation telling us what is
happening, or might
happen, to our bodies in time. Other factors include the impact
of our environment - what we eat and chemicals we are exposed to - and
also what is going
on in certain proteins in our body.
The sooner we normalize the storyline about DNA, the faster
genetics will take its rightful place in our science and in our
imaginations as one of
several remarkable and critical elements that make us who we are
- and what we might become in the future.
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Minnesotans Weigh Pros and Cons of Breakthrough Genetic Testing Technology
Lynn Fellman
stares at a computer in her warehouse-district art studio, tapping on
the keyboard as images of a human face expand and contract on the
screen.
“I'm just
trying to get this sized right,” she says. Cheekbones and hair pop in
and out of view. “I want it nice and crisp,” she explains.
Lynn is a
Minneapolis artist, inspired by international science. “I have a real
curiosity,” she says, as a string of numbers and letters sprawl across
the human face’s head. “Those are the letters of our code. Here’s his
sequence right here.”
Sequence, as in genome sequence.
“I work with
scientists to communicate their research through design and narrative,”
Lynn says, as face after face fills the screen, each with a different
code applied artistically across or behind it.
By definition,
genome is a collection of a person’s genes — all of the DNA in every
single cell. Half is inherited from mom, half from dad. Some of it
simply serves a structural role in the human body, some of it has been
influenced by viruses picked up over the course of a million years, and
some of it -- when sequenced by science and analyzed by experts -- will
tell us what diseases we’re either at risk of getting or are lurking
dormant deep within us. It’s what scientists refer to as our “genetic
burden.”
“This is
transformational for our species, and it's playing out right now in real
time,” Lynn says, as she tweaks her renderings of faces, each
representing a different gender, culture, and race. “Blew my mind. So
I’ve been developing work around that ever since.”
In fact, Lynn
is one of the very first people in the U.S. to sign up for something
called the Personal Genome Project (PGP). She’s one of eight Minnesotans
on a waiting list to have her entire genome sequenced. On her mother’s
side, there’s a history of hypertension and high cholesterol so “I
wonder if I’ll be seeing some markers in that when it comes up,” she
says. “The other area would be dementia. I saw that as I watched both my
parents grow old. So I’ll be looking to what the genome points to in
those regions."
“Who wouldn't want to be part of this revolution?” she asks. “This is an amazing story that's unfolding.”
GENETIC TESTING VS. GENOME SEQUENCING
Genome
sequencing is similar to genetic testing, but on a much broader scale.
Since the 1990s, DNA has been analyzed for solving crimes, determining
paternity and delving into ancestry. Every newborn in the U.S. is tested
for about 40 genetic abnormalities. And in recent years, people have
been able to test small samples of their genes for potential medical
problems. According to Matt Bower, a genetic counselor at the University
of Minnesota, “It may be that several family members have had breast
cancer or ovarian cancer or colon cancer and they want to know ‘Am I at a
higher risk than other people in the population?’ With genetic testing
they are generally very focused questions and we have very focused tests
that we think do a reasonable job of answering those questions.
“And so, for
example, if you find out you’ve got a BRCA1 or BRCA2 mutation there's a
very good body of evidence saying what we should be doing as far as
screening, how effective are surgeries like mastectomy at reducing that
risk, and other very actionable steps that people have studied and shown
to reduce the risk quite significantly,” he explains.
However, in
contrast to genome sequencing, the genetic testing scale is miniscule.
“Imagine the genome being 3 billion letters of code divided into 20
thousand functional genes,” Bower says. But in the search for breast
cancer risk, “we are looking for two out of those 20 thousand.”
Genetics is one
little gene at a time, one specific little instruction at a time, Bower
explains. “Genome is sort of taking off the blinders and looking at
everything at once. It's a very, very different focus. It’s trying to
open a big Pandora's Box of what are all the things that could happen to
you in the future.”
According to
George Church, who heads the Personal Genome Project from Harvard
University in Boston, “The amount of data you get out of genome
sequencing--reliable predictable data--is gigantic. You can think of it
as 2,500 tests rather than four.“
It's likely
that most, if not all of those tests will be negative for many people
“but that doesn't mean you don't take them,” Church says. He compares
sequencing to an annual physical exam at the doctor’s office. “You get
your blood pressure checked as a precaution, even if it might be
unlikely you’ll have a problem there.”
Church
continues, “But even if you think you don’t have a significant family
history, many people are the first in their family to have a genetic
disease. You might be the one who is. I mean, 10 percent of us in the
general population will be severely affected by medically actionable,
preventable genetic diseases in our lifetime.
“I think the
really compelling use for it for the average person is finding out
whether there is something that you need to do,” Church says.
BUT FEW HAVE BEEN ABLE TO AFFORD IT
It’s unclear
how many people around the world have actually had their entire genome
sequenced, in part because many keep the results private and there is no
official record or accounting. Since it first became an option in the
early 2000s, some researchers put the number at around 30,000; others
say far fewer, mainly because of the cost. Just a few years ago, people
were paying upwards of $350,000. Originally, it was in the millions of
dollars.
But now, thanks
to companies like Illumina and Knome, consumer-grade testing can be
done for $3,000 to $4,000 per person. In the next few years, the price
is expected to drop even further.
Still, getting
your genome sequenced is actually just the beginning of the process. It
then needs to be read, understood, and analyzed.
“They’re only
able to tell you the minimum amount of information,” Church says of the
direct-to-consumer companies. “They can tell you things that are
currently predictive and actionable. But then you have to talk to your
physician about it. And your physician might have to call in a
specialist.”
Bower adds,
“Right now I don't think there's a lot of practical application.” He
says if most people were to walk into most doctors’ offices with their
genome sequence and announce “here are three billion letters of genetic
code,” almost all of them would have no idea what to say, much less do
with it.
JOINING THE PERSONAL GENOME PROJECT
In George
Church’s Harvard laboratory, a dozen researchers work calmly and quietly
on the Personal Genome Project, in what might easily be called the
international nerve center of genome studies.
Church explains
that once a person’s genome is sequenced, “We put it together with
their medical traits, and what we know about their environment.” It’s a
lengthy and complicated process, all in the name of scientific
discovery.
The goal of the
PGP is to ultimately sequence the genomes of more than 100,000 people.
All who volunteers will be sequenced free of charge; the one caveat is
that their results will become part of the PGP’s publicly-available
research data base. “This isn’t a service,” Church points out, “it’s a
study designed to benefit society.”
Right now,
however, the number of people who’ve actually gotten their genome
sequenced through the PGP stands at just 40 people.
Initially,
there was concern about how the results might affect a person’s health
insurance. That dissuaded many potential volunteers. But then, Congress
passed the Genetic Information Nondiscrimination Act in the late 2000s.
“At the time they passed the law they could discriminate based on
pre-existing conditions,” Church explains. “Now, no matter how they
learn about your genetics, whether they ask you, whether they do it
surreptitiously, whether they find it out from your brother, they can't
use it. It's illegal.”
Today, a lack
of sufficient funding and grant money is the reason for so few completed
PGP sequences. “What's limiting us is our ability to pay for all the
costs of getting the sequencing done,” Church explains. “The more money
we have the more people we can do.”
All the science
aside, one of the most important questions for people considering
getting their genome sequenced is this: Am I prepared to deal with the
potential anxiety that these results might create?
For some, like
Church himself, there ends up being little cause for worry. He says his
genome revealed, among other information, that he has an extremely low
risk of ever developing Alzheimer’s Disease. “Not that I have a lot of
Alzheimer’s in my family but it was nice to know,” he says. “It was a
tremendous relief.”
However, Kirk
Maxie of Ann Arbor, Michigan says his results revealed he has variants
or mutations associated with risks for diabetes and anemia. Along with
Church, he is among the first 40 PGP participants to get the full genome
analysis.
Yet Maxie, who
says he’s otherwise perfectly healthy, isn’t particularly worried
either. “Learning all this might initially raise your anxiety but
knowing that you're at risk for some disease then allows you to modify
your health, your environment, your medicines, and your exercise
regiments to try to prevent that. So it's hopeful. It’s hopeful to know
that you can try to avoid it.”
About 2,000
people are currently on the PGP’s sequencing waiting list, including
Minneapolis artist Lynn Fellman. To qualify, she had to pass a written
exam testing her genome knowledge, and have blood and saliva samples
taken. She’s been waiting to learn the contents of her genome for about
two years.
In late April,
Fellman and about 130 other PGP participants from around the country
joined researchers and scientists at Harvard for the annual DNA Day
Conference that George Church organizes. There, they learned about the
most recent breakthrough technologies in the field. It’s also where Karl
Budd signed up to participate. A recent graduate of Minnesota’s
Shattuck-St. Mary’s School in Faribault, Budd says that part of his
interest stems from the fact he’s a bit of a hypochondriac. And he’s
only half-joking.
“Maybe it’s a
false sense of control,” he says, as nurses take his blood sample. “But
having the kind of knowledge your genome provides makes you think ‘oh,
I’m not going to get prostate cancer down the road’.”
Maxie
clarifies, “DNA isn’t destiny.” It’s what one does with the genome
information, he says, that helps define one’s future. “I mean, it
actually gives you some control over your life and your destiny.”
STILL, THERE ARE LIMITATIONS
Bower is among the genetic experts holding off on getting his own genome sequenced. He’s not a skeptic, just a realist.
“What it's
really just doing,” he says, “is modifying risks for a whole bunch of
diseases that we're all at risk for anyway. Often how they’ll report
this to you is they’ll say, ‘well, everyone has a one or two percent
lifetime risk of this condition. You have a variant that makes it two to
four percent. So, there’s a 96 percent or greater chance you won’t get
it—or you can be dramatic and say your risk has been doubled.”
He continues,
“Whether it's cancer or Parkinson's or Alzheimer's, we all have a risk
for these and what this is really telling us is ‘your risk is a tiny bit
bigger or a tiny bit lower than everybody else out there’. And I, for
me, just don't see the point. It wouldn't help me live my life any
better.”
So, what would
convince him to act? “Maybe if I knew i would have a big risk of colon
cancer and there was one variant that told me you need to be getting
screened 20 years before people I would do that. But I don't think it
would really help me to know all these potential risks when there's
really not a whole lot concrete i can do to modify a lot of them.”
Bower also
points out that genome sequencing still can’t address certain diseases
like Huntington’s, a neurodegenerative genetic disorder that affects
muscle coordination and leads to cognitive decline and psychiatric
problems. He explains, “If you wanted to know if you’re likely to get
Huntington's or not, I couldn't answer the question by sequencing your
genome. I absolutely could not because today's technology has
limitations and one of them is the type of genetic change that causes
Huntingtons is completely undetectable by this technology. The genome
technology actually misses the small piece of DN that actually causes
Huntington's.”
He adds, “For
Huntington's we go back to a test we've been doing since 1993. And it
gives us a far more clear answer than anything you'll ever get from this
genome sequencing.”
SHOULD YOU GET SEQUENCED?
There’s also no
cure for Lou Gehrig’s Disease (also known as ALS or amyotrophic lateral
sclerosis), but that hasn’t stopped Twin Cities siblings Scott and
Marilyn Nelson from wanting genome sequencing. Their mother developed
the disease shortly before she died and they watched helplessly as she
struggled with it.
“Ten percent of
Lou Gehrig’s tends to be familial or inherited,” Scott says. “If I were
prone to it they can do more research on my genes, my specifics, to
help get them closer to a cure. Whatever progress they may make might
not help me but it will help the next generation.”
Marilyn says
having a better grasp on what’s in the genetic cards for her would make
her “look at the quality of my life and make some improvements on it
while I can. There’s more I might want to do—just live more I guess. If
more people know what’s out there, that’s inevitable, maybe they too
could make some changes in their lives before it’s too late.”
A few years
ago, the Nelsons and their six siblings had their first immersion into
genetic testing when they learned that many of them had a high risk of
BCRA 2. Marilyn and two of her sisters chose to have preventative
hysterectomies to try to avoid ovarian cancer. Shortly afterwards, one
of the Nelson sisters, as well as her daughter, chose to have
preventative mastectomies to try and stay a step ahead of breast cancer.
“We wanted the cancer in our family to stop with us,” Marilyn says.
But it didn’t.
Scott developed pancreatic cancer seven years ago. He’s a rare survivor.
“There’s always research being done to identify what are the genes and
combinations of genes that are actually causing things like this,” he
says. He believes having his genome sequenced will aid in that
discovery.
“This type of research allows us to do the kinds of things we thought was just science fiction five years ago,” he says.
Even Lynn
Fellman admits that, despite all her excitement, “there is a real gap”
between what her genome might tell her and what she’ll then be able to
do about it. If she learns she truly does have a high risk of dementia,
effective preventative and proactive health care responses are currently
limited. “Sure, I'll be scared,” she says, “because there's really no
way you can absolutely prepare for that emotionally. But I would be kind
of glad to have that knowledge ahead of time and I could make some
plans, learn how to manage that better.”
Genome results
can also present indicators still undiscovered by science. In Kirk
Maxie’s case, “I have one single structural mutation within the coding
region of the genes. So it means one of the proteins that is used to
build me and my neurons is clearly defected. It's wrong. it doesn't look
right,” he explains. It’s a mutation that researchers have yet to
identify. “It’s a mistake for which no disease is yet known,” he
continues. In other words: a potential future mystery disease.
THE FUTURE
Sequencing the
first genome has led thousands of scientists to ask thousands of
questions, pushing forth many previously unexplored areas of medical
research. As more and more people get their own genome sequenced, still
more progress will be made.
“We're just at
the tip of the iceberg of figuring out what the actual code of all
these genes is,” says Bower, “and there's going to be so many layers of
complexity beyond that. I think it's a fair analogy to say it's going to
fundamentally change medicine.”
As for Lynn
Fellman, she’ll patiently remain hard at work on her genome-inspired
art, patiently waiting in the PGP line to get her own sequencing done.
“This is very emotional, intimate, personal stuff,” she says, describing
both her art and the science of genomics.
When the call does finally come, she says, “I’m good and ready for whatever comes of it.”
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Israel to subsidize costly genetic tests for high-risk pregnancies
The Health Ministry has decided to subsidize the chromosomal
microarray analysis, at a cost to the state of an estimated NIS 2
million to NIS 3 million a year. Starting Tuesday, women with high-risk pregnancies will be allowed
to undergo a free advanced genetic test designed for the prenatal
diagnosis of genetic abnormalities that other tests are unable to find.
Until now, the test was available only through private medical centers, at a cost of NIS 3,500 to NIS 5,000.
The Health Ministry has decided to subsidize the chromosomal
microarray analysis, at a cost to the state of an estimated NIS 2
million to NIS 3 million a year. The noninvasive test uses DNA chips to
test unborn babies for more than 270 genetic syndromes , subject to the
recommendation of a geneticist.
"The advanced test checks the genes using a
far more precise method" than existing genetic tests like amniocentesis
and chorionic villus sampling, said Joel Zlotogora, who heads the
Health Ministry's community genetics department.
Zlotogora said the new test would be done
if an ultrasound or other tests indicate a possible abnormality, and is
meant to complement amniocentesis, which is invasive.
"If we see on the ultrasound that the fetus
has an abnormality, we want to see for sure whether it's something
genetic," he said. "The whole world is deliberating whether to allow
most women to use this test, but right now no country is replacing the
basic tests with this one."
Zlotogora said the test was not being
offered to all women because it can show abnormalities that could
needlessly worry pregnant women and their partners, and lead to
increased abortions.
"We sometimes see things that have no
significance for the fetus, insignificant abnormalities," said
Zlotogora. "Some parents are likely to get scared off by the information
and end the pregnancy."
He said a large portion of fetal abnormalities can be fixed after birth.
Zdroj: web
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Genetic mutation may explain mysterious blond Solomon Islanders
When Sean Myles worked as post-doctoral student in Carlos
Bustamante’s lab, he showed Bustamante a photo of a Melanesian child
with cocoa-colored skin and bright blond hair, wearing a U.S. military
jacket.
Like others, Bustamante,a professor of genetics at
Stanford University, initially believed the Melanesians’ blond hair came
from Europeans who visited the islands and paired with islanders. But
Myles, now an assistant professor at the Nova Scotia Agricultural
College, insisted it was something different. When Myles had visited the
Solomon Islands for another research project, he estimated that 5 to 10
percent of the children possessed light locks. So Bustamante and Myles
designed an experiment to understand the origin of the blond Solomon
Islanders.
“I think there was some debate that the scientific community was sort
of hypothesizing about,” says Eimear Kenny, a co-author and
post-doctoral scholar in Bustamante’s lab at Stanford.
Bustamante,
Myles, and their colleagues discovered the Melanesians’ blond hair
comes from a gene mutation specific only to them. The variant is
recessive, meaning that both a mother and father must carry the gene for
a child to inherit flaxen hair.
“It is interesting to have one
gene that is associated with pigmentation in a tropical population with
blond hair,” says Rasmus Nielsen, professor of integrative biology at
the University of California, Berkley, who is not part of this
study. “There are lots of different mutations that impact skin and hair
color and in this case there is one mutation that impacts it, which is
quite unusual.”
In 2009, Myles collected 1,000 samples by
traveling from village to village on the Solomon Islands, working with
local chiefs for permission. The researchers first tested 100 samples to
look for genetic mutations and were shocked to find one gene
contributed to the blond hair—and this gene differed from what caused
blondness in Northern Europeans and their descendants.
The test of
the remaining 1,000 samples yielded the same results. The researchers
noticed a signal on chromosome 9 and when they dug deeper, they
discovered that TYRP1 , known for influencing pigmentation in mice and
humans, caused the blond hair.
“Pretty much everything about these
results was surprising. This is really not what we were expecting,”
says Kenny. “We did not expect to find a single gene.”
Generally, a
number of genes contribute to skin or hair color, for example. There
could be anywhere from 10 to hundreds of genes impacting whether a
person is blond.
While this discovery might appear to answer a
simple question, the results have larger implications. Most genetic
studies look at North Americans or Europeans and researchers translate
the results to represent all people.
“[This impacts] how we think
about the design of medical genetic studies and the importance of
broadening representations in medical studies,” Bustamante says.
And Nielson believes that researchers will gain a better understanding of the human genome by rethinking experiments.
“You can look at small isolated populations and find very interesting genetic variants,” Nielson says.
Zdroj: web
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Genes are no crystal ball for disease risk
The human genetic instruction book is as lousy at predicting disease
as an almanac is at predicting the weather, a prominent cancer
researcher concludes from an analysis of the genetic data from thousands
of pairs of identical twins.
A technological revolution has made deciphering genetic instruction
books, called genomes, quicker and cheaper than ever before. Many
scientists have touted the genome as a crystal ball for peering into
people’s medical futures. But Bert Vogelstein of Johns Hopkins
University School of Medicine wondered just how informative knowing a
person’s genetic makeup could be.
So Vogelstein and his colleagues gathered medical data from 53,666
twin pairs from around the world. Identical twins share their genetic
makeup, so looking at one twin’s health history may reveal what medical
complications the other twin's genome has in store. The researchers did
not decipher any of the twins' genomes but used the medical data to
develop a mathematical formula to predict the minimum and maximum risk
of getting 24 different diseases, including several cancers, heart
disease, diabetes and Alzheimer’s disease.
For all but four diseases, the genetic data would fail to determine
who is likely to contract the condition in most cases, Vogelstein
reported April 2 at the annual meeting of the American Association for
Cancer Research. The results were also published online April 2 in Science Translational Medicine .
“Basically, you can still do better just by putting somebody on the
scales and asking about their smoking history,” says Walter Willett, an
epidemiologist at the Harvard School of Public Health who was not part
of the study.
Under the team’s criteria, a test result was considered positive if
it shows that a person has a 10 percent or greater chance of developing a
particular disease. For most of the diseases, only a small fraction of
people would get a positive test result, the researchers found.
For ovarian cancer, for example, only 1 percent to 23 percent of
women who will eventually develop the cancer would get a positive
result. So, most women who will get ovarian cancer would have received a
negative test result.
That’s because genetics are only part of the story when it comes to
determining health. Lifestyle, environment and random chance play a
bigger role than genes, or work with genes, to cause or protect against
disease.
But for the small number of people who do get a positive test result,
such information could be very important. “Even if the majority of
individuals will receive negative test results, you don't know until you
check,” says George Church, a Harvard geneticist and founder of the
Personal Genome Project, an effort to catalog genomes and relate genetic
variation to individual traits. “It is analogous to fire insurance. You
don't know in advance if you are in the majority who will not lose
their house.”
Doctors, especially those who treat cancer, have already been through
passionate debates about the value of genetic testing, says
Olufunmilayo Olopade, director of the Cancer Risk Clinic for University
of Chicago Medicine. The more doctors and scientists know about genomes,
the better they can advise and treat patients, she said.
But Vogelstein said that he and his colleagues aren’t making a value
judgment about the usefulness of genome sequencing. “What we’re trying
to do is simply introduce a reality check,” he said.
Zdroj: web
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Experimental AIDS therapy may be beginning of the end
One step closer to a cure for AIDS – that is the implication of
results out Wednesday from from several leading research centers.
It
should be noted that many people involved in AIDS research, including
several who carried out the latest research, avoid the “c” word. Their
goal is to allow people infected with HIV to live without daily doses of
the medications that usually keep the virus under control-- at a large
financial cost --and a risk of side effects.
The latest work,
published in Science Translational Medicine, details 43 HIV-infected
volunteers who had experimental genes inserted into their
disease-fighting white blood cells 11 years ago. All patients are doing
fine. After more than a decade with this gene therapy , there are no side
effects. In almost every one the inserted genes are still working
properly.
While these experiments were never intended to treat or cure
anything, they lay the groundwork for gene therapy that could have a
substantial impact on HIV disease.
A cure for AIDS became an
obvious goal as soon as the disease was discovered 30 years ago. But it
became “the dirty four letter word,” as Jon Cohen of Science magazine
put it, after some spectacular failures. Soon after the powerful
cocktail of anti-AIDS drugs came on the market in 1996, some scientists
speculated they could use the drugs to knock out all the infection in
the body. But that idea crashed as repeated experiments showed that
pockets of infected cells hid in various parts of the body, emerging
quickly as soon as the drugs were withdrawn.
HIV has infected some 50 million people in the world and none has been cured -- except perhaps Timothy Ray Brown.
It
was the case of Brown, also known as “the Berlin patient,” that
energized the new search for a cure. Infected with HIV, Brown was dying
not of that disease, but of leukemia. His only hope was a bone marrow
transplant – first killing, then replacing all the cells in his body
that make blood cells with those from a donor. Brown’s doctor Gero
Hütter was not an AIDS specialist, but he knew that about 1 percent of
people of European decent have a mutation in a receptor called CCR5 on
certain white blood cells that make HIV infection very difficult. So the
doctor sought a donor with that mutation.
The transplant took
place in 2007. In 2010 Hütter published his results. Not only had the
transplant eliminated Brown’s leukemia, he no longer needed to take his
HIV medications and the most sophisticated tests find no trace of HIV in
his body.
A transplant with a serious risk of death, costing more
than $250,000, will not be a treatment for a disease contained by
medications. But the case raised the possibility that modifying the
white blood cells with gene therapy might do the trick. Several
experiments are underway in both animals and humans and more are
planned.
The latest research shows the gene therapy can be safe in
the long term. Whatever we call it, we may be at the beginning of the
end of AIDS.
Zdroj: web
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California Genetic Privacy Bill Moves Forward – Padilla’s SB 1267 to Protect a Person’s DNA
California’s Senate Judiciary Committee today passed Senate Bill
1267, authored by Senator Alex Padilla (D-Pacoima). The bill would
establish the California Genetic Information Privacy Act. The measure
now goes to the Senate Appropriations Committee for consideration.
Presently, there are no laws that prevent surreptitious taking,
testing and disseminating an individual’s genetic material and
information. Specifically, SB 1267 would provide that no genetic
material can be collected, analyzed, shared and stored without a
person’s written consent. The bill would impose civil and criminal
penalties and fines for taking and testing a person’s genetic material.
“SB 1267 would extend California privacy protections to a person’s
genetic material and information,” said Senator Alex Padilla. “We have
laws to protect the privacy of our financial information, our medical
records, and even the books we check out from the local library. We need
genetic privacy protections because nothing is more personal than our
DNA,” added Senator Padilla.
Genomic sequencing and testing is fast approaching the point where it
will be widely affordable to the general public and an integral part of
health care. What took years of international effort to produce in the
mid-1980’s can now be completed in days. Analysis of genetic material
can allow for early detection of disease long before symptoms become
apparent. Genetic markers can also suggest propensity for diseases that
may or may not ever develop.
“No one should be able to take another person’s DNA without consent
and mine it for information. We look forward to working with Senator
Padilla to pass strong legislation to protect every Californian from
unauthorized testing of their DNA,” said Jeremy Gruber, President,
Council for Responsible Genetics.
“As genetic testing becomes more accessible there is an increased
risk of this information being used without consent. No person should
have their genetic material taken, tested and given to others without
written consent. All Californians should have these basic protections,”
added Senator Padilla.
Recently, the Minnesota Department of Health, in Bearder v. State of
Minnesota, was sued for collecting the blood of infants, conducting
genetic analysis and storing the information without the consent or
knowledge of their parents. The information was ultimately passed on to
researchers. The court found that the Department had violated
Minnesota’s Genetic Privacy Act, a 2006 law that requires informed,
written consent for the collection, storage, use and dissemination of
any genetic information. The Minnesota Department of Health now must
destroy the thousands of samples that they collected and stored.
Last year the Governor signed Senate Bill 559 (Padilla), which
expanded California civil rights laws by prohibiting discrimination
based on genetic information in housing, employment, education, public
accommodations, health insurance coverage, life insurance coverage,
mortgage lending, and elections.
Senator Alex Padilla, 39, graduated from MIT with a degree in
Mechanical Engineering. He currently serves on the MIT Board. He is
Chair of the Senate Energy, Utilities and Communications Committee and
represents the more than 900,000 residents of the 20th State Senate
District which includes most of the San Fernando Valley in Los Angeles.
Zdroj: web
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Genetic testing and disease: Would you want to know?
Kristen Powers finishes packing her lunch and opens the kitchen door to leave for high school with her brother, Nate, in tow.
"I drive but always let him pick the music," she says, smiling.
He gives her a gentle nudge and they set off to the car.
Nothing
like having a kid brother behind you, especially when you are embarking
on a courageous journey. Kristen, 18, is having blood work done May 18
to find out whether she inherited the defective gene for Huntington's
disease, a fatal, neurodegenerative disorder that can debilitate victims
as early as their mid-30s. The siblings have a 50-50 chance of
developing the rare disease, which claimed their mother's life last year
at age 45.
Nate, 16, doesn't know whether
he'll follow his sister's lead. Only people 18 or older can be tested,
unless they're exhibiting symptoms, because a positive result can be
shattering news. There's also no cure. Huntington's is devastating on so
many levels: People lose coordination, developing wild jerky movements;
they suffer behavioral changes, often becoming depressed and psychotic;
and in the end, they develop dementia and require total care. One of
their last images of their mother was in a wheelchair in a nursing home.
Nate "has been amazingly supportive of my
wanting to get tested," Kristen says. "He is interested in the whole
process, but he's been hesitant over the years to commit to testing,
while I've known since I was 15 that I wanted to do this."
"Know
thyself" has taken on a scientific meaning for a growing number of
people who, like Kristen, want a crystal ball to look into their DNA.
Ever since the Human Genome Project
identified the 20,000 to 25,000 genes in 2003, researchers have
continued to identify the ones that play roles in diseases, from
Alzheimer's to type 2 diabetes to certain types of cancer. Though
lifestyle and environment are big pieces of the puzzle, consider this:
Genetic tests could become part of standard care for everyone and
revolutionize the way medicine is practiced, proponents say.
Gone would be the days of waiting to develop a disease. People would
know about diseases they are at risk for and could change their living
habits or consider treatments. Opponents warn about the potential for
invasion of privacy — threatening employment and insurance — and the
possibility that people equipped with the knowledge of their genetic
makeup might make risky and unhealthy decisions.
Kristen has had counseling at the University of North Carolina
to prepare her for dealing with her testing news, and she copes with
stress by walking with her rescue dog, Jake. "Walking is critical for
me," she says. She will return to the campus at the end of May with her
father, Ed Powers, to get the results.
"She's
always wanted to take matters into her own hands," her father says.
"She's constantly asking what we can do to make things better. I am her
biggest backer and want to be there for her every step of the way during
this."
Leaning on social media
Kristen
leans on her kitchen table and explains in a quiet, clear voice that
she is ready to handle the news and has no plans to keep it secret.
"I
started out trying to find answers on the Internet about Huntington's
disease," she says, "but I quickly became very disappointed. There's not
a good video or an advocate for it, like Michael J. Fox is for Parkinson's disease."
She
has raised $17,580 on the website Indiegogo.com and hired a video crew
to make a documentary about the emotional and medical aspects of
testing on her and her family. "Social media can be a real unifier.
There's not much out there yet for young people on Huntington's. I want
to change that."
Her mother, Nicola Powers,
was diagnosed in 2003 after struggling with symptoms for several years.
"I remember watching her stumble and walk like a drunk person at times,"
Kristen says. "That was before we knew what was wrong with her. She was
really struggling. It was very scary."
Nicola
Powers didn't know the disease ran in her family. She grew apart from
her biological father after her parents divorced. Once she looked into
his medical history because of her symptoms, she discovered he had
Huntington's.
Kristen doesn't want the gene
to be passed on again. She says she won't have children if she tests
positive: "I can be candid with potential partners and be responsible,"
she says.
Genetic counselors warn about the emotional impact of testing on the person and family.
"Some
people like to plan everything out," says Brenda Finucane, president of
the National Society of Genetic Counselors. "They think the information
is empowering, while some people want to see how life plays out."
Robert Green
has found that most people will not seek out risk information about
late-onset Alzheimer's disease if they're not psychologically prepared
to handle it.
But "it turns out many people
handle this kind of information quite well," says Green, associate
director for research in genetics at Brigham and Women's Hospital in
Boston. "Some changed their wills, and some made lifestyle changes.
Taking these tests is all about actionability."
Timing
can be tricky, though. Kristen's father and stepmother, Betsy Banks
Saul, suggested she hold off until she has a support system at college.
"She's a very intelligent, strong young woman and we trust her, but we
wish we could be nearby to support her," Betsy says.
After
high school graduation in June, she will attend Stanford, in California
— far from her farm, family and friends. Kristen listened to her
parents' concerns and considered putting off testing, "but I am a type A
person who has always craved getting information. I want to know."
Not all tests are equal
Her
test will look for the single gene that causes Huntington's, but most
diseases have a more complicated genetic profile. A growing number of
tests look at multiple genes that might increase or decrease a person's
risk for developing thousands of diseases. Companies market the tests
for as little as $100 on the Internet and don't require a physician's
signature. But those kinds of results are not always reliable, says
Ardis Dee Hoven, former chair of the American Medical Association .
"In
the absence of a medical professional, a patient might have difficulty
interpreting the test and make decisions that are not healthy
decisions," Hoven says.
For instance, someone
who tests negative for BRCA1 and BRCA2 — genes that put people at a
higher risk for developing certain breast and ovarian cancers — might
not know there are other risk factors. Unless the patient has a
physician guiding her, Hoven says, she might think she's home-free and
skip routine screening tests.
David Agus, author of the new book The End of Illness ,
says that's why the company he co-founded, Navigenics, requires
customers to get a signature from their doctors before being tested.
Navigenics also offers genetic counseling as part of the $300-$400 fee.
"Genetics
are a small piece of the puzzle, but they're a very important piece,"
says Agus, head of the Center for Applied Molecular Medicine at the University of Southern California .
A
cancer specialist, Agus discovered he has an above-average risk for
cardiovascular disease and a slightly lower-than-average risk for colon
cancer. His doctor put him on a statin to help prevent heart disease,
and, he says, "my kids took it upon themselves to keep me away from
french fries." He also had a colonoscopy at age 43, earlier than medical
standards call for, and had a polyp removed. "Could my polyp have
turned into cancer? Who knows? But why should I wait for that to happen?
Unless our country can focus on prevention, which testing is all about,
our health care costs will be completely out of control."
A study of 1,200 patients that was presented in March at an American College of Cardiology
meeting found that those who were told they had a gene linked to heart
disease improved their adherence to statin therapy by 13% compared with
those who had not been tested for the gene.
"I
could see how testing could become embedded in how we treat our
patients," Hoven says. "It's always better to prevent disease than to
treat it, and quality of life is so much better for people."
How accessibility could change
Since
the human genome was unraveled a dozen years ago, genetic testing has
been cost-prohibitive for the average person. The promise was that this
breakthrough would lead to a better understanding of myriad diseases
and, ultimately, individualized treatments. Whole genome testing studies
the interaction of our 20,000 to 25,000 genes with one another and with
a person's environment. The $10,000 price tag, though, is expected to
drop to $1,000 within the decade. When the tests become mainstream,
doctors could face a dilemma.
A study in
March reports that 10 of 16 specialists (62%) favored telling a
patient he carried the gene for Huntington's if the finding was
incidental to why the test was ordered. The study noted that the
specialists unanimously agreed on disclosing 21 of 99 commonly ordered
genetic conditions for adults, and "multiple expert panels" might be
needed to agree on what to tell patients.
"This
is one of the toughest issues facing the rollout of clinical sequencing
(whole genome sequencing)," Green says. He adds that after the study,
he co-chaired a forum March 28 of the American College of Medical
Genetics to discuss how to form a consensus.
That's
a non-issue for Kristen. She knows she will get an answer. One of her
hardest decisions has been picking who will be in the room when she gets
her results. She knows she wants the videographers taping. At first she
didn't want her father to be there, but she relented when he asked her
to reconsider.
"I know I can take the news,"
she says, "Knowledge is power. But I didn't think I could get a positive
result and then watch my father cry. I've never seen him cry before."
Zdroj: USA Today
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Synthetic Genetics
The genetic basis for life on Earth may be stored in RNA and
DNA, but scientists have now made six synthetic mimics of genetic
material that are capable of recording, propagating, and evolving
genetic information (Science, DOI: 10.1126/science.1217622 ).
The mimics could form a rudimentary basis for synthetic life and may
have applications in materials science, molecular diagnostics, and
therapeutics, comments Gerald F. Joyce ,
a chemist at Scripps Research Institute in La Jolla, Calif. They may
also inform the search for life on other planets and for the origin of
life on our own, he says.
A team led by Philipp Holliger ,
a chemist at the Medical Research Council Laboratory of Molecular
Biology in Cambridge, England, prepared RNA and DNA mimics from six
existing analogs of ribose and deoxyribose, the sugars that form the
polymer backbones of RNA and DNA, respectively.
Like ribo- and deoxyribonucleotides, the nucleotide versions of these
analogs can be strung together to form six different polymer backbones
that the researchers call xeno-nucleic acids (XNAs) . These are versions
of nucleic acids containing nonnatural ring structures in place of
ribose or deoxyribose. Each XNA can present sequences of the four
genetic bases in DNA—cytosine, guanine, adenine, and thymine.
The team spent three years engineering and evolving polymerases that
can copy a genetic code from DNA to an XNA and then back to DNA, a feat
that mimics heredity, Holliger says. The team also showed that the
synthetic genetic polymers could undergo Darwinian evolution when
subjected to selection pressure. For example, the researchers evolved
genetic polymer sequences based on 1,5-anhydrohexitol (see ring in
HNA)to bind to specific protein and RNA targets.
“In the longer run, it may be possible to design and build new forms
of life that are based on one or more of these nonnatural genetic
polymers,” comments Jack W. Szostak , who studies the origin of life at Harvard Medical School.
“Synthetic biologists are beginning to frolic on the worlds of
alternative genetics but must not tread into areas that have the
potential to harm our biology,” Joyce cautions. However, before the
synthetic genetic polymers could form life, “the XNA must be able to
catalyze its own replication without the aid of biological molecules,”
and this would be a challenging task, Joyce notes.
For now, Holliger says his group is focused on biomedical and
biotechnical applications. For example, he hopes to evolve the XNAs so
that they fold into three-dimensional structures that can perform a
task, such as delivering a drug to a cancer cell. Because the XNAs are
synthetic polymers , “they can’t be degraded by nucleases, which would
target RNA and DNA,” he says.
Furthermore, the team hopes to make use of the fact that the XNAs can
be evolved to exhibit certain functions. In principle, Holliger says,
“if you want the XNAs to deliver a drug inside cells, you could just
select them to go into cells.”
Finally, the synthetic genetic polymers could be used as tools to
figure out why, in the primordial soup, ribonucleic acids succeeded in
becoming the first molecules of life, when many molecules were competing
for the job. “Phil’s work will certainly make it possible to compare
the functional abilities of a wide range of synthetic nonbiological
nucleic acids” with those of RNA and DNA to answer this question,
Szostak notes.
Zdroj: web
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Bigger Brain and Higher IQ Linked with Specific Genetic Variants
Researchers have identified two genes that affect brain size and may
be linked not only to IQ, but also to our risk of developing brain
disorders like Alzheimer’s disease.
Scientists have known for some time that the size and volume of
certain parts of the brain are linked to disorders including
developmental conditions such as autism and degenerative diseases like
Alzheimer’s. The brains of autistic children, for example, tend to be bigger than those of unaffected youngsters, and in Alzheimer’s patients , the brain region responsible for memory, the hippocampus, tends to be smaller .
But what influences brain size to begin with? It’s a feature that is
highly heritable among humans, suggesting that genes may play a role.
That suggests in turn that such genes may also influence vulnerability
to any number of mental disorders that are linked to brain size, above
and beyond the genes that directly affect memory or language skills, for
example.
So researchers involved in the Enhancing Neuro Imaging Genetics
through Meta-Analysis (ENIGMA) Consortium — more than 200 scientists
from 100 institutions worldwide — decided to figure out which genes are
responsible for brain size (with the assumption that they would then
predispose people to brain disorders) by combining two powerful
techniques: genome-wide analyses of disease-related genetic variants and brain imaging .
The researchers looked at MRI scans of the brain structures of 21,000
people, both with disorders including depression, anxiety, Alzheimer’s
and schizophrenia, or without these conditions and compared them to
genetic surveys of the DNA changes linked to these disorders.
Even the researchers were surprised by how well the strategy worked:
they found two genetic variants, one that appears to be associated with
overall brain size and another that was linked to the volume of the
hippocampus, or memory center, which typically shrinks in people with
dementia.
“None of these changes on their own will give you disease,” says the
study’s senior author, Paul Thompson, professor of neurology and
psychiatry at UCLA Medical School, of the group’s findings, published in
Nature Genetics . “But they vastly tilt the scales in favor of disease.”
People who had the genetic variant associated with smaller
hippocampus volumes had shrinkage equivalent to about five years of
aging, Thompson said, meaning that whatever degradation in brain
functions — memory, learning or attention — that occur with aging would
be accelerated. That’s even after accounting for the known factors that
can affect brain volumes, including ethnicity, height and other physical
attributes.
One copy of the gene variant conferred a 1.3% reduction in
hippocampal volume, while two copies, one from each parent, doubled that
shrinkage. With normal aging, the brain loses about 0.5% of tissue a
year, but the variant that Thompson and his colleagues discovered sped
up that process considerably, potentially making the person more
vulnerable to developing age-related disorders, including Alzheimer’s.
“We know what the variant of this gene looks like — the carriers of
this new gene look like their brains are five years older than they
should be,” says Thompson. “This is a major genetic discovery that makes
that much of a difference on a brain scan. We don’t yet know whether
the loss of tissue tilts the sales to people to have increased risk of
Alzheimer’s disease, but it gives you a very strong lead.”
The other variant the team isolated was related to overall brain
volume and was linked to a 1.3-point change in IQ. The effect of the
gene on IQ scores was small, but significant — enough to show up on an
IQ test. However, the authors note that there are many contributors to
brain size and IQ, such as a good education, exercise and other
environmental factors, which would outweigh the effect of this single
gene variant.
The idea is to use these two variants as a starting point for
thinking about how to improve diagnosis and eventually treatment of
brain disorders, says Thompson. With Alzheimer’s, for example, experts
believe that people can use brain-boosting techniques like exercise,
continuing education and social interaction to reinforce existing nerve
networks and build up a cognitive reserve
— like a savings account for the brain. As the brain’s networks start
to deteriorate naturally with age, it can call on its reserves to
compensate for the loss of tissue and still function reasonably well.
People with the genetic variants isolated in the ENIGMA study,
however, may have a smaller reserve due to their genetically influenced
brain structures, and may therefore be more vulnerable to any
environmental factors, such as obesity or excessive alcohol consumption,
that further reduces brain volumes. “We all experience slow erosion of
the brain by an army of culprits,” says Thompson. “And that army
includes your genes. The relief platoon includes how much you invest in
exercise, a good diet and education. So those two forces are basically
in opposition.”
What’s encouraging about the results is that they hint that brain
scans can be a powerful indicator of gene activity, or a way of tracking
how certain genes are functioning and possibly contributing to disease —
well before any symptoms appear. “These findings are a very, very big
lead for brain health,” says Thompson, “and they can help our
understanding of what we might do to prevent brain decline.”
Zdroj: web
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Genetics leads to cancer break through
Scientists say they've made an unexpected discovery that will help
doctors personalize treatment for one of the deadliest forms of breast
cancer
A team of researchers in British Columbia, Alberta, the United States
and the U.K. mapped the genetic profile of what's called triple-negative
breast cancer, the largest genetic analysis of its kind.
A news release from Simon Fraser University, where four of the
researchers in the study are based, said the 59 scientists involved in
the study expected to see similar gene profiles when they mapped the
genomes of 100 tumours.
But they found no two genomes were similar, never mind the same.
"Seeing these tumours at a molecular level has taught us we're dealing
with a continuum of different types of breast cancer here, not just
one," Steven Jones, co-author of the study, said in a news release.
Jones is a molecular biology and biochemistry professor who heads up
bioinformatics research at the BC Cancer Agency. He said discovering the
genetic diversity of the tumours "probably explains why they are so
difficult to treat."
"These findings prove the importance of personalizing cancer drug
treatment so that it targets the genetic make up of a particular tumour
rather than presuming one therapy can treat multiple, similar-looking
tumours."
The study was published Wednesday in the online edition of the journal Nature.
Triple-negative breast cancer is considered the most deadly form of
breast cancer because it doesn't respond well to drugs and requires
surgery, chemotherapy and radiation. Patients with that form of breast
cancer usually end up having everything thrown at them in an effort to
push the cancer into remission.
Prof. Samuel Aparicio, another of the paper's authors who teaches at
the University of British Columbia and works at the BC Cancer Agency,
cautioned the paper's conclusions won't mean quick changes for anyone in
treatment for this type of cancer now.
He said for 15 to 20 per cent of patients, it may mean additional options beyond the current existing treatments.
"The efficacy of these options now needs to be tested directly in clinical trials," he said.
"We didn't know they existed before. We are hoping to do this if we get
funded and that would lead to a change in practice if the outcomes were
positive."
For the remaining patients, the research gives some indication of the
types of drugs that need to be developed to treat the tumours.
"That will take time, but there is a path forward that we can see," said Aparicio.
"The main pointer here is that we will have to learn how to combine
drugs from the outset, as is done in treating diseases like HIV for
example, where combination therapies have become very successful."
B.C. Labour Minister Margaret MacDiarmid, a past president of the BC
Medical Association, was diagnosed with the disease a few years ago and
said the discovery is groundbreaking.
"It's an amazing announcement. It's hard not to take it personally
because, yes, I did have triple-negative cancer," she said. "I was
diagnosed, fortunately for me, at a very early stage. I have no sign of
any problems from it, but it is one of the most deadly forms of breast
cancer."
She said the announcement gives hope to those suffering from the disease.
Zdroj: web
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A New Warning Against Genetic Testing
If you follow health news, you've heard talk about a person's "genetic
risk" of disease. With companies offering personalized genetic tests for
as little as $200, it's tempting to think that a world of knowledge is
at our fingertips.
But a new paper from some of the leading names in science throws a bit of cold water on the promise.
According
to a group from Johns Hopkins University, led by two scientists known
for breakthrough discoveries on the genetics of cancer, genomic
sequencing "fails to provide informative guidance to most people about
their risk for most common diseases." The problem, they say, is
not the state of current technology and knowledge -- which is limited --
but a more basic problem: genetics plays a surprisingly small role in
determining the chances that we'll get sick. Score one for the
environment.
That's why, at this point in time, "prudent
screening, early diagnosis and prevention strategies, such as not
smoking and removing early cancers, will be the keys to cutting disease
death rate," according to Dr.Bert Vogelstein, M.D.,co-director of the
Ludwig Center for Cancer Genetics at Johns Hopkins Kimmel Cancer Center.
He
says that if someone is relying on a whole genome test to be the
crystal ball that predicts their likelihood of getting cancer, they will
be disappointed.
Experts are also concerned about people ordering
genomes off the Internet. If someone receives information without the
proper context from a doctor or genetic counselor, it could give them a
false sense of security and stop them from taking preventative measures.
Nicholas
Roberts, one of the study authors and a graduate student at Johns
Hopkins says that even in the best case scenario, the majority of people
who have their whole genome tested will get a negative test result -
that means the results do not reveal any genes that cause cancer.
But that doesn't mean they won't get cancer. More than just genes contribute to someone getting the disease.
Nathan
Pearson, director of research at Knome, a company that sequences whole
genomes for researchers, praised the study and said it helps to think of
our genes as being like a musical score. Two performers can be seeing
the same notes in front of them, yet sound quite different.
"There are many different renditions," says Pearson. "You can improvise."
Pearson explains what he found when he sequenced the genome of Ozzy Osbourne.
To
reach their conclusion, the Hopkins group performed a set of
straightforward calculations, based on the studies of identical
twins. They looked at the strength of the link between genes and disease
for each of 24 different ailments. As they point out, "[Identical]
twins in general do not always develop or die from the same maladies."
While
their tone is cautious, they point out that some common diseases have a
much stronger genetic component than others. Based on twin studies,
genetic testing might some day predict more than 90% of coronary heart
disease deaths in men, and more than 90% of all Alzheimer's cases. By
contrast, testing could predict fewer than a third of lung cancers,
breast cancers, leukemia and ovarian cancers.
These figures are
based on a "best-case scenario," in which complete genomes have been
examined for millions or tens of millions of individuals. The state of
knowledge today is much more primitive. According to Pearson, current
genetic testing is most useful when analyzing individual cancer cells,
or in finding the causes of rare diseases, in which a single mutation
leads to devastating results.
Some pitches seem to promise more.
The website of 23AndMe, a company which offers genetic tests directly to
consumers, urges people to "Take a more active role in managing your
health," and promises that "knowing your genes may impact your health,
can help you plan for the future and personalize your healthcare with
your doctor." 23AndMe does not analyze the full genome of its customers,
but rather sections of the genome whose influence is relatively
well-known.
Henry Louis Gates, Jr. on 23AndMe and genetic testing for African-Americans
David
Hinds, principal scientist for statistical genetics at 23AndMe, says
the company makes sure that customers don't expect too much.
"At
this stage the presumption is that this testing has no clinical
utility." He agreed with the paper's authors, who say genetic tests will
never replace current disease prevention strategies. "It's just another
piece of information."
Zdroj: web
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Genetic mutation depicted in van Gogh’s sunflower paintings unearthed by scientists
Those fluffy-looking sunflowers captured so poetically in Vincent van
Gogh’s famous paintings are garnering attention in the world of plant
genetics.
In a study published in PLoS Genetics (Public
Library of Science), a team of University of Georgia scientists announce
they have found the genetic mutation that’s responsible for the
distinctive, “double flowers” that appear in the iconic painter’s
Sunflower series.
“I’ve worked on sunflowers for the past 10 to15 years and have thus
really come to appreciate this series of paintings,” says University of
Georgia professor of plant biology John Burke.
Van Gogh began painting sunflowers while living in Paris in 1887,
mostly as clippings. A year later in Arles, France, he began painting
the flowers in vases — a project to decorate the bedroom of his friend
French Post-Impressionist artist Paul Gauguin.
“We have identified the gene (HaCYC2c) that is responsible for mutant
phenotype that van Gogh captured in several of his sunflower
paintings,” he says.
Burke has identified the gene mutation responsible for van Gogh’s
double headed flowers. “There are naturally occurring mutations,” says
Burke “As far as we know sometimes things go wrong. We wanted to figure
out genetically — why.”
Even the official website for the van Gogh Gallery acknowledges there
is something peculiar about those flowers, painted in two series — some
as cut flowers and some in vases. On the subject of van Gogh’s
sunflowers, the website acknowledges, “it is difficult to say how
accurate van Gogh’s paintings are.”
It compares those flowers painted by van Gogh to photographs of
traditional looking sunflowers, pointing out differences in petal
structure and colour. “This is due to the various stages that sunflowers
go through, endless genetic features and natural flaws,” the site
explains. “The unrealistic aspects of his paintings could be quite
realistic when examined through the right variables.”
Enter Burke.
He’s convinced the sunflowers painted by the post-Impressionistic
artist were realistic. While the most common “garden variety” sunflowers
reveal a large singular flower head surrounded by a ring of florets —
the mutated “double-flowered” sunflowers appear like a large dandelion.
Van Gogh’s peculiar-looking sunflowers could have been the result of
crossbreeding, a wild sunflower, for example, with a “double-flowered
variety.”
At around the same time van Gogh was painting in the south of France,
Gregor Mendel, a 19th century pioneer of genetics in plants, was
tinkering with floral morphology and the resulting changes in plant
architecture. It’s part of a long-standing tradition of crop
domestication — “transforming weedy plants into useful crops.”
For example the wild sunflower is recognizable by its “loose
branching” with multiple flowers. This branching phenomenon also occurs
in wild corn (maise), a trait that’s eliminated once domesticated.
Sunflowers are big business — appreciated for their oil, their edible
seeds and their commercial use as ornamental flowers. Burke and his
team wanted to get to the genetic basis of this “reasonably important
economic trade.”
But van Gogh’s unusual sunflowers were most likely the result of a natural mutation, says Burke.
Zdroj: web
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Research uncovers genetic marker for PRRS elimination
A collaborative discovery involving Kansas State University
researchers may improve animal health and save the U.S. pork industry
millions of dollars each year.
Raymond "Bob" Rowland, a virologist and professor of diagnostic
medicine and pathobiology, was part of the collaborative effort that
discovered a genetic marker that identifies pigs with reduced
susceptibility to porcine reproductive and respiratory syndrome, or
PRRS. This virus costs the U.S. pork industry more than $600 million
each year.
"This discovery is what you call a first-first," Rowland said. "This
discovery is the first of its kind for PRRS but also for any large food
animal infectious disease. I have worked in the field for 20 years and
this is one of the biggest advances I have seen."
Rowland and researchers Jack Dekkers from Iowa State University and
Joan Lunney from the Agricultural Research Service discovered a genetic
marker called a quantitative trait locus, or QTL, which is associated
with porcine reproductive and respiratory syndrome virus susceptibility.
This discovery is a first step in controlling and eliminating the
virus.
The research recently appeared in the Journal of Animal Science. The
project's beginning and future center around Kansas State University,
Rowland said.
It begins at the university because Rowland is involved with an
organization called the PRRS Host Genetics Consortium, or PHGC, which
initiated and provided more than $5 million for the research. Rowland is
co-director of the consortium, which is a collaboration among the
United States Department of Agriculture, the National Pork Board and
Genome Canada as well as universities and industry members. Rowland is
also director of the USDA-funded PRRS Coordinated Agriculture Project,
known as PRRS CAP.
"The PRRS Host Genetics Consortium takes fundamental science and turns it into utility," Rowland said.
Kansas State University's new Large Animal Research Center is the
site of much of the project's experimental work. The researchers obtain
multiple measurements -- including growth, weight gain, performance and
virus measurements -- over time. They have collected samples from more
than 2,000 pigs since they began the study in 2007, for a total of
more than 100,000 samples that are stored or distributed to the
consortium's collaborators.
The university shipped samples to the Agricultural Research Service
for genomic DNA preparations to identify differences among more than
60,000 genes. The data was transferred to Iowa State University for
genetic analysis that led to the discovery of the QTL.
The collaborators at Iowa State University created a common database
so that all the data collected during the project can be accessed at
multiple locations by researchers and the breeding industry for the next
several decades.
"A unique aspect of this project is that we have been looking at
genes that may provide long-term resistance to a lot of infections,"
Rowland said. "This is very important for animal health because there
are a lot of diseases for which there are no cures and no vaccines. Now
we have a tool to study these diseases."
These findings open new possibilities with Kansas State University's
Biosecurity Research Institute and the future National Bio and
Agro-defense Facility. Scientists can take this new genetic tool and
study different infectious diseases in these world-class research
facilities.
The discovery plays a role in nearly every aspect of animal health
and is a large economic driver, Rowland said. Industry members are
especially interested in how it opens new possibilities with vaccines.
The next step is to find which genes contribute to the best vaccine
response.
"We're not only making healthier animals, but we're also
understanding the fundamental biological relationship between a host and
a pathogen," Rowland said. "This has direct applications to human
medicine because the same type of science and relationships applies to
humans."
In addition to providing a better model for the porcine reproductive
and respiratory syndrome virus, the research has led to several
spin-offs:
The Kansas State University researchers are able to collect
thousands of samples that companies need to validate and develop the
next generation of diagnostic tests. One such test is the use of oral
fluids -- a noninvasive diagnostic test in which pigs chew on a rope and
scientists analyze the saliva left on the rope. The research led to the discovery of pigs with severe combined
immunodeficiency, or SCID. This research should enable researchers to
better study the syndrome and apply its use to the study of human cancer
and anti-cancer drugs.
The project has also proved to be very valuable for education because
it has involved more than 20 veterinary medicine, pre-veterinary
medicine and graduate students at Kansas State University.
"This is an incredible opportunity for students to come in, learn how
to work with animals, learn basic biosecurity and have the opportunity
to do research," Rowland said. "It provides them with a lot of
practical hands-on knowledge."
Other Kansas State University collaborators involved include the
Veterinary Diagnostic Laboratory and Carol Wyatt, associate professor of
diagnostic medicine and pathobiology.
Zdroj: web
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Tune in, tone up
Genetics matter but there's still much you can do to obtain the body you want, writes Isobel King.
It was so much easier in Rubens's day, when the folds and
dimples of the ''full-figured'' woman were objects of lust and there
was zero pressure to achieve the rippling abs and chiselled lines we
sweat over today. While tempting to think we could all become perfectly
proportioned models with just a little bit of work, the reality is only
about 5 per cent to 10 per cent of women are in the height and weight
range of models, and the average Australian woman is now a size 16.
Little surprise that so many of us are plagued by poor body image and
unrealistic ideas of what is achievable, given the strong hand genetics
play in our basic body shape.
Shape shifters
The good news is you can do a lot with the cards dealt to
you. Admittedly, you can't suddenly spring long legs or determine where
your excesses cling to you but with focused toning, you can
dramatically alter what you have.
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''You can't spot-reduce, as the way you lose fat is
genetically determined,'' says a dietitian and exercise physiologist,
Gabrielle Maston. ''For example, if you tend to hold weight in the hips,
then that's probably the last place you'll lose it. However, you can
give a different appearance to your body without changing body-fat
stores, just by getting more toned, reducing or adding muscle bulk.''
The one caveat health and fitness coach Amelia Burton
adds - echoed by others S.Well spoke to - is that you need to shed
excess weight to get the best results. If you're more than five
kilograms to eight kilograms overweight, you really need to look at
shifting that, either before or in tandem with any toning regime.
Here's a rundown of how you can target problem areas with specific exercises.
Shapely legs
We'd all kill for Miranda Kerr's legs but few are that
blessed genetically. However, there are many exercises you can do in and
outside a gym to achieve more muscle bulk or simply a longer, leaner
look to your legs.
Maston points out that sprinters tend to have muscly
legs, whereas long-distance runners have lean legs, so depending on the
look you're after, you want to look at exercises that mimic these
sports. Or take up running.
Burton recommends backward-stepping lunges, which are
part of most pump classes: literally a step backwards, with the back
knee almost touching the floor. ''They elongate out the muscles, giving
long and lean shaped legs, and are also good for the butt,'' she says.
Cycling and spin classes are also great for the legs but
be mindful of what you want to achieve. The more resistance you add, the
more muscle bulk you'll build. Go for greater repetitions with less
resistance if you're after a slender, toned look.
Killer abs
Much has been written about the importance of a strong
''core'' - the inner and outer back and abdominal muscles that surround
and support the torso. A strong core not only leads to better posture
but also easier breathing and, hopefully, a nice six-pack.
Yoga and Pilates both work on building core strength and
many of their techniques have been incorporated into popular gym
classes. The ubiquitous ''plank'', for example, has its origins in yoga,
says the vice-president of Yoga Australia, Leigh Blashki.
Many variations exist but the most common is the front
plank, which is held in a push-up position with the body's weight
resting on forearms, elbows and toes; and the side plank, where you lie
on your side and push up, carrying the weight on your elbow and forearm,
working the muscles along the side of your body (the obliques). In its
many guises, the plank is universally heralded as one of the best
workouts for the abs.
Not surprisingly, the core-strengthening focus of Pilates
is also recommended highly. Pilates practitioner William Penhale
describes it as a ''body balancer'' that addresses the muscular system
as a whole, working first on the deeper layer of abdominal muscles, then
moving the focus to the bigger muscles on the exterior.
''You're more inclined to get the long, lithe look of a
dancer, rather than the bunched-up look of a body builder, with
Pilates,'' Penhale says.
Upper body
Both Burton and Maston recommend swimming as a great
natural workout for the upper body. For men, it gives them the coveted
V-shaped back, encouraging big shoulders and a lean waist. It also helps
strengthen the triceps - the back of the upper arms that, when
neglected, easily become dreaded ''tuck shop arms''. To replicate the
effects at the gym, Maston suggests rowing and the lat pull-down
machines.
Boxing and kickboxing are also great for upper- and
lower-body resistance. Using light weights with lots of repetitions will
stop you bulking up.
How much is enough?
It's always a point of contention: exactly how much do
you have to work out to get results? A lot has to do with the intensity
put into a workout and just how much definition you're after.
Maston recommends 30 minutes to one hour, at least three
times a week, with the hope you'll feel a difference within six weeks
and visibly see changes within about 12 weeks. ''But with exercise it
has to be consistent,'' she warns. ''If you stop going, you'll revert to
where you were before.''
On the upside, she says a body of any age can respond
positively to weights and aerobic training, developing new-found muscle
tone.
Burton is similarly upbeat. ''Body shape is 50 per cent
what your parents gave you and 50 per cent what you put into it, so no
one has to settle for what genetics have handed them,'' she says.
Body of hard work
''I just felt there was a better version of me in there,'' Nisha Agiasotis says about what sparked her personal transformation.
The 33-year-old mother of two says she comes from a
family in which ''all the women carry weight around the belly'', so a
prime objective was to get a slender, toned abdomen along with shapely
shoulders and biceps.
First, she dropped 10 kilograms to achieve her target
weight of 45 kilograms, which was a comfortable fit for her slight,
153-centimetre frame. Then she embarked on a rigorous gym routine to
achieve the toned look she was after, using the 12-week Advanced Lean
and Strong program devised by personal trainer Michelle Bridges
(12wbt.com).
Motivated to see quick results, Agiasotis put in an hour a
day, six days a week, at the gym and says she started to see new
definition in about a month.
''I was adamant I didn't want to lose more weight, just
tone up,'' she says. With her weight stable, she found the waists of
her jeans were roomier and her muscles firmer.
By the end of the 12 weeks, Agiasotis achieved the athletic body she has today.
For the benefit of those similarly inspired, she lists
her exhaustive weight training: ''Barbell squats, body-weight squats,
lunges and weighted lunges, planks, chin-ups, push-ups and push-ups
with claps, barbell chest-press, dumb-bell flies, bicep curls and
hammer curls, tricep pull-downs and tricep dips, leg extensions,
hamstring curls, calf raises, seated rows and pull-downs.''
The results speak for themselves.
Zdroj: web
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Genetics & The Mind-Body Connection
Given the constant bombardment of often conflicting health
information we get these days, having the technology to tell us exactly
what to do and when to do it would seem almost too good to be true. But
not according to Dr. David Agus , author of the bestselling book, The End of Illness .
Anyone who signs up to take one of his DNA-based Navigenic
tests receives a detailed analysis of his or her genetic predisposition
to various health conditions and medications. This provides the
individual with a detailed outline of what it will take to stay healthy
for as long as possible. Kind of like the 1950’s TV show, “This Is Your Life ,” only in reverse.
While I may be oversimplifying things a bit, the assumption seems to
be that once you understand your genetic makeup, you have a pretty clear
idea of who you are and who you will be as a person; that is, from a
purely physical standpoint. What appears to be missing, however, is any
allowance for changes in your genetic makeup and what factors, if any,
you can control.
For most, the idea that your genes can change – once, or even many
times – within a single lifetime sounds pretty crazy. But there’s some
hard evidence indicating that it can happen. A study conducted at the Benson-Henry Institute for Mind Body Medicine
at Massachusetts General Hospital found that things like meditation,
tai chi, yoga, exercise, and prayer can alter a person’s gene activity,
especially as it relates to stress. Considering that more than 60% of visits to doctors are for stress-related complaints, this is pretty significant stuff.
I asked Dr. Agus about this apparent link between mind and body at a recent talk
he gave to The Commonwealth Club of California. He said, “There’s no
question that the mind-body connection is real, even if we can’t
quantify it. Hope is one of the greatest weapons we have to fight
disease.”
Had the conversation continued, I would have liked to get his take on
other disease-fighting weapons such as gratitude, forgiveness, and
love; qualities of thought that, according to a growing number of
researchers, can have a very real – and quantifiable – impact on your health.
I can recall a time when some debilitating back pain I was
experiencing completely disappeared shortly after I made a conscious
effort to be more tolerant of others. On another occasion, the
acknowledgement of my God-given purity coincided quite nicely with the
healing of a painful skin infection. It just didn’t make sense to me
that something I consider to be infinitely pure would allow even the
slightest element of impurity to occur within its infinite creation.
All of which points back to something Dr. Agus said towards the end of his talk…
“The single most important thing you can do to maintain your health
is to add regularity to your daily routine.” Although he was referring
to things like diet and exercise, I took it as a reminder to myself to
routinely watch what I’m thinking. Time and again I’ve seen the impact
this can have on my health and general well being, not to mention my
relationships with others. This, in turn, tends to make them happier
and healthier as well. And so on, and so on…
Zdroj: web
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Men respond more aggressively than women to stress and it's all down to a single gene
The pulse quickens, the heart pounds and adrenalin courses through the
veins, but in stressful situations is our reaction controlled by our
genes, and does it differ between the sexes? Australian scientists,
writing in BioEssays , believe the SRY gene, which directs male
development, may promote aggression and other traditionally male
behavioural traits resulting in the fight-or-flight reaction to stress.
Research has shown how the body reacts to stress by activating the adrenal glands
which secrete catecholamine hormones into the bloodstream and trigger
the aggressive fight-or-flight response. However, the majority of
studies into this process have focused on men and have not considered
different responses between the sexes.
"Historically
males and females
have been under different selection pressures which are reflected by
biochemical and behavioural differences between the sexes," said Dr
Joohyung Lee, from the Prince Henry's Institute in Melbourne. "The
aggressive fight-or-flight reaction is more dominant in men, while women
predominantly adopt a less aggressive tend-and-befriend response."
Dr Lee and co-author Professor Vincent Harley, propose that the
Y-chromosome gene SRY reveals a genetic underpinning for this difference
due to its role in controlling a group of neurotransmitters known as
catecholamines. Professor Harley's earlier research had shown that SRY
is a sex-determining gene which directs the prenatal development of the
testes, which in turn secrete hormones which masculinise the developing
body.
"If the
SRY gene
is absent the testes do not form and the foetus develops as a female.
People long thought that SRY's only function was to form the testes"
said Professor Harley. "Then we found SRY protein in the human brain and with UCLA researchers led by Professor Eric Vilain, showed that the protein controls movement in males via dopamine."
"Besides the testes, SRY protein is present in a number of
vital organs
in the male body, including the heart, lungs and brain, indicating it
has a role beyond early sex determination," said Dr Lee. "This suggests
SRY exerts male-specific effects in tissues outside the testis, such as
regulating cardiovascular function and neural activity, both of which
play a vital role in our response to stress."
The authors propose that SRY may prime organs in the male body to
respond to stress through increased release of catecholamine and blood
flow to organs, as well as promoting aggression and increased movement
which drive fight-or-flight in males. In females oestrogen and the
activation of internal opiates, which the body uses to control pain, may
prevent aggressive responses.
The role of SRY regulation of catecholamines also suggests the gene
may have a role in male-biased disorders such as Parkinson's disease.
"New evidence indicates that the SRY gene exerts 'maleness' by
acting directly on the brain and peripheral tissues to regulate movement
and blood pressure in males," concluded Lee. "This research helps
uncover the genetic basis to explain what predisposes men and women to
certain behavioural phenotypes and neuropsychiatric disorders."
Zdroj: web
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Exercise changes the genetic identity of your muscle cells
New research may change the way we view our DNA and its ability to
change. This could not only help improve the benefits of exercising, but
also combat cancer and neurodegenerative diseases. Researchers from
the Novo Nordisk Foundation Center for Metabolic Research at the
University of Copenhagen, Karolinska Institute and Dublin University
are behind the scientific breakthrough, which has just been published
in the renowned scientific journal Cell.
Researchers have long known that during exercise a genetic change in
your muscle cells make the tissue better at burning fat and sugar. And
it is this temporary betterment, which gradually makes the muscles
stronger. Now researchers have made the remarkable discovery, that the
genetic change in the muscle cell is so fundamental as to be compared to
embryogenesis itself.
“Each of the billions of cell in the human body contains a perfect
copy of that persons DNA, which is like a private cook book with
numerous different recipes or genes,” says Assistant Professor Romain
Barrès from the Novo Nordisk Foundation Center for Basic Metabolic Research .
“What makes a skin cell different from, say, an eye cell or a muscle
cell, are certain molecular bookmarks that are placed at different
locations in the book and glue together the pages containing the recipes
this particular cell does not need. A skin cell, for example, does not
need to produce insulin, while a pancreatic cell should not produce
pigment.”
Genetic book mark gives cells their identity
This book-mark is chemically seen a methyl-group, and this molecule
gives each cell its identity. The methyl-groups are remodelled during
embryogenesis, where they orchestrates the growth from stem cells to
specified cells, and it is what makes your eye cells work as eye cells,
pancreas cells as pancreas cells and skin cells as skin cells.
“We set out to understand what, biochemically speaking, happened in a
muscle cell, to change the genes, so the muscles better burn fuel,”
says Professor Juleen Zierath from University of Copenhagen and
Karolinska Institute.
“And to our great surprise, it was the cellular identity tag, the
methyl -group, which un-glues certain pages in the DNA cookbook so the
cell starts producing enzymes that increase fuel burning in the
surrounding muscle tissue. Who could have thought that something so
fundamental as methyl groups, which in essence defines how your own
personal DNA expresses itself in your own body, also partakes in
something as transient as fuel burning? Because it is only when you
move, that these pages are open – so to speak. When you stop exercising,
the pages are glued back together almost instantly.”
Exercise manipulates cell identity
“It’s always been thought that tampering with this
methyl-identity-tag in the DNA would lead to all kinds of trouble,”
Romain Barrès continues. “But we have shown, that just by exercising,
you, yourself manipulate the DNA of your cells. Our DNA is not as stable
and unchangeable as previously thought.”
The researchers point out that these methyl-groups plays a role in
healthy as well as diseased cells, and it opens up for completely new
venues of research and possibilities.
“These methyl-molecules are also remodelled in cancer cells,” Juleen
Zierath says. “So what would happen, if we could start manipulating
with the identity of a cancer cell? Can we change it? Or what would
happen if we could change the identity of a neurodegenerate brain cell?
Could we help repair it?”
Pharmaceutical manipulation of cell identity could boost benefit of exercise
“Or imagine getting the same effect of six hours of rock climbing
from just 15 minutes on the running track,” Romain Barrès says. “We
also want to enhance the beneficial effects of exercising, which we know
protects against obesity, diabetes, cancer, high blood pressure,
depression and more. Something which is more important than ever with
the global diabetes- and obesity-epidemics, where we need
pharmaceuticals which can deal with the way we live and work today.”
The article “Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle ” is published in the magazine CELL METABOLISM on 7 March 2012.
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Computing with soup
Molecular computing: DNA is sometimes called the
software of life. Now it is being used to build computers that can run
inside cells EVER since the advent of the integrated circuit in the 1960s, computing
has been synonymous with chips of solid silicon. But some researchers
have been taking an alternative approach: building liquid computers
using DNA and its cousin RNA, the naturally occurring nucleic-acid
molecules that encode genetic information inside cells. Rather than
encoding ones and zeroes into high and low voltages that switch
transistors on and off, the idea is to use high and low concentrations
of these molecules to propagate signals through a kind of computational
soup.
Computing with nucleic acids is much slower than using transistors.
Unlike silicon chips, however, DNA-based computers could be made small
enough to operate inside cells and control their activity. “If you can
programme events at a molecular level in cells, you can cure or kill
cells which are sick or in trouble and leave the other ones intact. You
cannot do this with electronics,” says Luca Cardelli of Microsoft’s
research centre in Cambridge, England, where the software giant is
developing tools for designing molecular circuits.
At the heart of such circuits is Watson-Crick base pairing, the
chemical Velcro that binds together the two strands of DNA’s double
helix. The four chemical “bases” (the letters of the genetic alphabet)
that form the rungs of the helix stick together in complementary pairs: A
(adenine) with T (thymine), and C (cytosine) with G (guanine). By
making single strands of DNA or RNA with specific A, T, C and G
sequences, researchers can precisely define and predict which part of a
strand will bind to another. These synthesised strands typically consist
of fewer than 100 bases (a gene, by contrast, has thousands of bases).
Leonard Adleman, an American computer scientist, first demonstrated
the use of nucleic-acid strand interactions for computing in 1994. He
solved a version of the travelling-salesman problem—given a network of
linked cities, what is the shortest route that visits each city exactly
once?—in a test tube using specially sequenced DNA molecules and
standard molecular-biology procedures (see box). Solving such a specific
task is a far cry from building a general-purpose computer. But it
showed that information could indeed be processed using interactions
between strands of synthetic DNA.
Dr Adleman’s work prompted other researchers to develop DNA-based
logic circuits, the fundamental building blocks of computing, using a
variety of approaches. The resulting circuits can perform simple
mathematical and logical operations, recognise patterns based on
incomplete data and play simple games. Molecular circuits can even
detect and respond to a disease signature inside a living cell, opening
up the possibility of medical treatments based on man-made molecular
software.
Liquid logic
Erik Winfree’s group at the California Institute of Technology
(Caltech) is one of the best-known in this emerging field. In recent
years it has made many nucleic acid-based digital logic circuits in test
tubes, linking up logic gates capable of simple operations (such as
AND, OR and NOT) using a trick called strand displacement, pioneered by
three Caltech researchers, Georg Seelig, David Soloveichik and Dave
Zhang.
In a strand-displacement logic circuit, inputs take the form of
free-floating single DNA or RNA strands, and logic gates are complexes
of two or more such strands, one of which is the potential output
signal. “Sticky” tabs on the gates allow passing signals to latch on. If
an input signal has a base-pair sequence complementary to the sequence
on a gate, it binds to it, displacing the output strand and causing it
to detach. The free-floating output strand can then, in turn, trigger
another logic gate, causing a signal to travel through the circuit in a
cascade. Billions of copies of the input, gate and output molecules are
intermixed in a molecular soup. Programming such a system involves
choosing specific base sequences to make up the different gates and the
signal paths that connect them.
In a paper published last year in the journal Science ,
Dr Winfree and his colleague Lulu Qian described the use of
strand-displacement cascades to build circuits of increasing complexity,
culminating in a circuit made of 74 different DNA strands (pictured)
that was capable of calculating the square roots of four-digit binary
numbers. Together with their colleague Jehoshua Bruck, they then built a
tiny neural network, made up of four interconnected artificial neurons,
using a soup of 112 different interacting DNA strands. Each neuron was
designed to fire when the sum of its input signals exceeded a certain
threshold, and could be configured to assign different weights to
different inputs. Such neural networks can recognise simple patterns,
even when presented with incomplete data.
To test their neural network’s pattern-recognition powers, Dr Qian
made up a game to identify one out of four scientists. Each scientist
was represented by a different set of answers to four yes-or-no
questions. A human player would add to the test tube some (but not all)
of the DNA strands corresponding to one set of answers. The circuit then
guessed which scientist was the closest match, showing its answer using
different-coloured fluorescent signals. The circuit took eight hours to
give its answer, but got it right every time. And this circuit should
work in a volume of a cubic micron (one-millionth of a metre), says Dr
Winfree, which is small enough to fit into many sorts of cell.
Milan Stojanovic at Columbia University is building circuits using a
different form of strand displacement based on catalytic DNA strands,
also known as deoxyribozymes or DNAzymes. These are synthetic
single-stranded DNA sequences that are, among other things, capable of
cutting nearby DNA strands in specific places.
Dr Stojanovic makes a DNAzyme into a logic gate by attaching a loop
of DNA at one end that prevents the DNAzyme from working. When one or
more input strands bind to complementary sequences on the loop, the loop
breaks, activating the DNAzyme and switching the gate on. It can then
interact with other strands, chopping them to trigger other gates or
activate fluorescent tags that display the circuit’s final output. Dr
Stojanovic and his colleague Joanna Macdonald have used this approach to
build simple DNA-based circuits capable of playing tic-tac-toe (though
they take about half an hour to make each move).
Yannick Rondelez, a researcher in molecular programming at the
University of Tokyo, is creating circuits in test tubes in a way that
more closely resembles the operation of natural cells. He is using
enzymes such as polymerases, nucleases and exonucleases that can also
copy, cut and destroy nucleic-acid strands. In cells, enzymes are the
basis of the natural circuits that switch genes on and off, maintain
biological rhythms and produce molecular answers in response to
environmental stimuli. Dr Rondelez has used his enzyme-based approach to
build a molecular oscillator, which should be a useful addition to the
molecular-computing toolbox.
A group at the Swiss Federal Institute of Technology (ETH Zurich) led
by Yaakov Benenson, in collaboration with Ron Weiss of the
Massachusetts Institute of Technology, is also creating circuits using
enzymes. But unlike Dr Rondelez’s circuits, which work in test tubes,
these operate inside cells, piggybacking on the existing cellular
machinery found within them. Last year Dr Benenson’s team developed one
of the most complex cell-based molecular circuits created so far, though
it is still much simpler than systems built in test tubes. It is
capable of recognising the signature of cervical cancer and destroying
the host cell when it is found.
The circuit works by looking out for short strands called microRNAs,
which regulate some processes within cells. They do this by interfering
with the activity of the messenger RNA strands that transfer genetic
information from the cell’s nucleus to its protein-making machinery. Dr
Benenson and his team chose five microRNAs associated with cervical
cancer and designed a “classifier” circuit able to detect them. Only if
all five are found at the right levels does the circuit activate,
producing a protein that causes the cell to destroy itself.
Computer-aided DNA
Rather than injecting the necessary components, the researchers
tricked the cell into producing them itself by adding instructions for
them, in the form of synthetic genes, to the genetic instructions in the
cell’s nucleus. “We build the template in the form of synthetic genes
and the cell turns them into components,” says Dr Benenson. “So we are
hijacking the pathway that already exists.” But this trick is currently
possible only for simple circuits.
With molecular circuits becoming steadily more complex, new software
tools are being developed to design, model and debug them. Microsoft’s
researchers in Cambridge are working with experimentalists at Caltech,
the University of Washington and the University of Oxford on a
programming language and simulator for strand-displacement circuits,
called the DNA Strand Displacement (DSD) tool. Users specify a
description of a DNA-based circuit, including how individual DNA strands
are joined together, and the software then simulates its behaviour,
explains Andrew Phillips, the head of Microsoft’s biological-computation
group.
Dr Phillips’s group is also developing tools to model the machinery
within cells, including a language called Genetic Engineering of Cells
(GEC). Work is under way with synthetic-biology researchers at the
University of Cambridge to hook up these different biological modelling
environments. “You could have a model of a DNA circuit written in DSD,
which interfaces with a model of the cell machinery written in GEC,” he
says. It would then be possible to simulate the operation of a DNA
circuit that runs inside a cell and outputs drug molecules when certain
conditions are met, for example.
Treatments based on molecular computers are still some way off.
Today’s most elaborate DNA circuits operate on work benches, not inside
cells. But the border between computing and biology is vanishing fast,
and the process of hijacking the information-processing potential of DNA
to build logic circuits has only just begun.
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Rare Disease Day 2012
The National Human Genome Research Institute will
help raise the awareness of rare diseases by observing Rare Disease Day
on Wednesday, Feb. 29, 2012, as it participates in a daylong symposium
on the disorders. The event is coordinated in the United States by the
National Organization for Rare Disorders and is supported in part by the
NIH Office of Rare Diseases Research. This year's theme is Solidarity .
Nearly 30 million Americans are affected by one of 7,000 rare
diseases. About 80 percent of rare diseases are genetic in origin and
about 75 percent affect children. Rare diseases can be chronic,
progressive, debilitating, disabling and life-threatening. Information
is often scarce and research is usually insufficient. People affected
face numerous challenges, such as delays in obtaining a diagnosis,
misdiagnosis, psychological burden and lack of patient and family
support services. The goal of rare disease advocates is to obtain for
patients the highest attainable standard of health and the resources
required to overcome common obstacles in their lives.
Rare Disease Day at NIH (RDD@NIH)
On February 29, 2012, the National Institutes of Health (NIH) will
celebrate the 5th annual Rare Disease Day with a daylong symposium
focused on various rare diseases research supported by the NIH Office of
Rare Diseases Research, the NIH Clinical Center, NIH institutes and
centers, the Health Resources and Services Administration (HRSA), the
Food and Drug Administration's Office of Orphan Product Development
(OOPD), the National Organization for Rare Disorders (NORD), and the
Genetic Alliance.
Rare Disease Day at NIH (RDD@NIH) will be held in the Clinical
Center's Masur Auditorium (Building 10) from 8:30 a.m. to 5:00 p.m.
Attendance is free and open to the public. In addition to the various
scheduled talks, there will be posters and exhibits from many groups
involved in the rare diseases research community. Attendance is free and
open to the public. You can view the agenda here
While attendance is free, NIH would like to know how many people are
planning to attend to prepare accordingly. If you would like to display a
poster or exhibit, please include that information on your registration
form. You can contact Dr. David J. Eckstein at eckstein@od.nih.gov for more information.
The NIH Office of Rare Diseases Research encourages all attendees to
also plan on attending the Food and Drug Administration's Rare Disease
Day activities on March 1, 2012.
Visit the NIH Visitors and Security
website for the latest instructions and updates. Please allow 30
minutes to move through security. Sign language interpreters will be
provided. Individuals with disabilities who need reasonable
accommodation to participate in this event should contact Kimberly
Potter at kpotter@icfi.com or
301-251-4962 or the Federal TTY Relay number at 1-800-877-8339. Requests
should be made at least five days in advance of the event.
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Confused by genetic tests? NIH’s new online tool may help
An online tool launched today by the National Institutes of Health
will make it easier to navigate the rapidly changing landscape of
genetic tests. The free resource, called the Genetic Testing Registry
(GTR), is available at http://www.ncbi.nlm.nih.gov/gtr/ .
"I’m delighted that NIH has created this powerful, new tool. It is a
tremendous resource for all who are struggling to make sense of the
complex world of genetic testing," said NIH Director Francis S. Collins,
M.D., Ph.D., who unveiled GTR at NIH's observance of international Rare
Disease Day. "This registry will help a lot of people — from health
care professionals looking for answers to their patients’ diseases to
researchers seeking to identify gaps in scientific knowledge."
Genetic tests currently exist for about 2,500 diseases, and the field
continues to grow at an astonishing rate. To keep pace, GTR will be
updated frequently, using data voluntarily submitted by genetic test
providers. Such information will include the purpose of each genetic
test and its limitations; the name and location of the test provider;
whether it is a clinical or research test; what methods are used; and
what is measured. GTR will contain no confidential information about
people who receive genetic tests or individual test results.
Genetic tests that the Food and Drug Administration has cleared or
approved as safe and effective are identified in the GTR. However, most
laboratory developed tests currently do not require FDA premarket
review. Genetic test providers will be solely responsible for the
content and quality of the data they submit to GTR. NIH will not verify
the content, but will require submitters to agree to a code of conduct
that stipulates that the information they provide is accurate and
updated on an annual basis. If submitters do not adhere to this code,
NIH can take action, including requiring submitters to correct any
inaccuracies or to remove such information from GTR.
In addition to basic facts, GTR will offer detailed information on
analytic validity, which assesses how accurately and reliably the test
measures the genetic target; clinical validity, which assesses how
consistently and accurately the test detects or predicts the outcome of
interest; and information relating to the test’s clinical utility, or
how likely the test is to improve patient outcomes.
"Our new registry features a versatile search interface that allows
users to search by tests, conditions, genes, genetic mutations and
laboratories," said Wendy Rubinstein, M.D., Ph.D., director of GTR.
"What's more, we designed this tool to serve as a portal to other
medical genetics information, with context-specific links to practice
guidelines and a variety of genetic, scientific and literature resources
available through the National Library of Medicine at NIH."
GTR is built upon data pulled from the laboratory directory of
GeneTests, a pioneering NIH-funded resource that will be phased out over
the coming year. GTR is designed to contain more detailed information
than its predecessor, as well as to encompass a much broader range of
testing approaches, such as complex tests for genetic variations
associated with common diseases and with differing responses to drugs.
GeneReviews, which is the section of GeneTests that contains
peer-reviewed, clinical descriptions of more than 500 conditions, is
also now available through GTR.
The GTR database was developed by the National Center for
Biotechnology Information (NCBI), part of NIH’s National Library of
Medicine, under the oversight of the NIH Office of the Director and with
extensive input from researchers, testing labs, health care providers,
patients and other stakeholders. To view video tutorials on how to use
GTR, go to http://www.youtube.com/playlist?list=PL1C4A2AFF811F6F0B .
The Office of the Director, the central office at NIH, is responsible
for setting policy for NIH, which includes 27 Institutes and Centers.
This involves planning, managing, and coordinating the programs and
activities of all NIH components. The Office of the Director also
includes program offices which are responsible for stimulating specific
areas of research throughout NIH. Additional information is available at
http://www.nih.gov/icd/od/ .
NCBI creates public databases in molecular biology, conducts research
in computational biology, develops software tools for analyzing
molecular and genomic data, and disseminates biomedical information, all
for the better understanding of processes affecting human health and
disease. NCBI is a division of the National Library of Medicine , the world's largest library of the health sciences.
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Schizophrenia risk linked to common genetic variants
A quarter of the risk for developing schizophrenia can be traced to
genetic variations that are common in the general population, a study by
Queensland researchers has found.
A new method of genetic analysis developed by The University of
Queensland’s Queensland Brain Institute, in conjunction with The
University of Queensland Diamantina Institute and the Queensland
Institute of Medical Research, found that all people carry genetic
variants that contribute to the risk of schizophrenia.
But only people who carry many of those variants together are at substantial risk of being affected.
The chronic disorder, characterised by persistent delusions and
hallucinations, affects about one person in 100 at some point in their
lives and usually strikes in late adolescence or early adulthood.
The latest research into the disease, published in the journal Nature
Genetics, has shed light on its elusive genetic underpinnings, said the
study leader, Associate Professor Naomi Wray from the Queensland Brain
Institute.
“Not long ago people talked about finding "the gene” for
schizophrenia, then the “handful of genes”. Our research implies there
are many genetic factors acting together, and together with
environmental factors,“ Professor Wray said.
“If we all carry some risk variants then our systems are robust to
their effects – for example other pathways may compensate. Our results
suggest that affected people may carry a burden of risk variants that
means compensatory mechanisms can no longer cope.”
The researchers compared genetic variations in DNA known as
single-nucleotide polymorphisms across 9,087 people who had
schizophrenia and 12,171 people who did not.
They found that 23% of liability for the brain disorder could be
traced back to a set of variations, most of which are common in the
general population. The variance was shared equally between men and
women.
According to Professor Naomi Wray, this suggests that we all carry
genetic risk variants for schizophrenia, but that the disease only
emerges when the burden of variants, in combination with environmental
factors, reaches a certain tipping point.
Cannabis use is recognised as one environmental factor that contributes to the risk of developing schizophrenia.
Paul Fitzgerald, a Professor of Psychiatry at Monash Alfred
Psychiatry Research Centre, said the past 10 years of research into
schizophrenia had been characterised by “high hopes followed by
disappointing results. But this study provides some novel and promising
guidelines for how we can understand the causes of schizophrenia and
where we go from here.”
The findings suggested that variations in many hundreds of genes
contributed to the risk of developing schizophrenia, Professor
Fitzgerald said. “Variations in many of these genes, however, are
frequently found across all people and will be possible targets for
study to help develop new treatments.
“However, before this can occur we need to individually identify this
set of genes and this is likely to take studies with up to 50,000
patients and a similar number of controls.”
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Can You Be Fired for Your Genes?
In 2010, Pamela Fink, an employee of a Connecticut energy company,
made a new kind of discrimination claim: she charged that she had been
fired because she carries genes that predispose her to cancer. Fink
quickly became the public face for the cutting edge of civil rights:
genetic discrimination .
The Genetic Information Nondiscrimination Act, which was passed out
of concern for just such cases in the wake of huge advances in genetics
testing, took effect in late 2009. GINA, as it is known, makes it illegal
for employers to fire or refuse to hire workers based on their “genetic
information” — including genetic tests and family history of disease.
GINA doesn’t just apply to employers: health-insurance companies can be
sued for using genetic information to set rates or even just for
investigating people’s genes.
There have not been any landmark cases or huge jury awards yet under
GINA, but genetic discrimination is real. According to the Equal
Employment Opportunity Commission’s annual report ,
released last month, there were 245 genetic-discrimination complaints
in fiscal year 2011, up more than 20% from a year earlier. At the same
time, the EEOC reported that the “monetary benefits” it helped collect
related to genetic discrimination — in damages, back pay and other
penalties — jumped more than sixfold, from $80,000 to $500,000.
These numbers will almost certainly increase greatly in coming years.
Many people still do not know about their rights under GINA or even
what genetic discrimination is. There will also no doubt be more lawyers
developing genetic-discrimination practices. But the main reason these
claims are likely to rise is that, as biological science advances, there
is likely to be even more genetic information available about people.
Tests are getting better at identifying those who are predisposed to
cancer, heart disease and Alzheimer’s disease. Even though this sort of
medical information should remain private, employers and insurance
companies will have strong financial incentives to get access to it —
and to use it to avoid people who are most likely to get sick.
When genetic-discrimination claims start showing up in the courts in
significant numbers, they are likely to get a sympathetic hearing. This
is just the sort of civil right that there is the most support for. How
much? When Congress enacted GINA in 2008, the House of Representatives
supported it 414-1, and the Senate backed it unanimously.
There are two major reasons that so many people — even congressional
Republicans who are highly skeptical of civil rights laws — like GINA.
First, there is the kind of discrimination it is aimed at: penalizing
people for strands of DNA and RNA that they inherited from their parents
through no fault of their own. Discrimination law is a tricky thing:
there are no hard-and-fast rules for deciding what characteristics of a
person should be off-limits in deciding whether to hire them, rent them
an apartment or set their insurance rates. In general, our society has
decided to protect people for qualities that are “immutable” — that is,
something about them that is impossible or, at least, very difficult to
change.
So we make it illegal to discriminate on the basis of race, national
origin, skin color and sex. (And religion: in that case, people can
easily change faiths — we just don’t think they have to.) On the other
hand, we generally do not protect people who are not hired because they
lack a high school diploma or because they wear a beard. Our response to
those people is that if you want the job you should get more education
or shave. Genes are a classic immutable characteristic: outside of some
complicated medical procedures, we’re pretty much stuck with the genes
we were born with.
The second major reason genetic-discrimination laws are popular is that
this is a kind of bias everyone feels they could be exposed to. If you
are white, you may not think you will benefit from a law against racial
discrimination, and if you are straight you probably do not worry about
discrimination on the basis of sexual orientation. But none of us has
perfect genes — and for the most part, we have no idea what is lurking
in our DNA and RNA. Our genes are complex enough that we all have some
negative information encoded in there — and none of us wants to lose a
job or be denied insurance over it. When juries begin to hear these
cases, they are far more likely to identify with the plaintiffs than
with the companies that discriminate. That doesn’t mean that there won’t
be plenty of companies looking to benefit from genetic information, but
if they use it, they may well have to pay. Cohen, the author of Nothing to Fear , teaches at Yale Law School. The views expressed are solely his own.
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Gene fault linked to stroke risk
A “single genetic mutation can double your risk of stroke”, the Daily Mail has reported. The newspaper added that scientists hope the discovery could lead to tailored treatments for the condition.
The news is based on research which looked for genetic variations that were more common in people who had had an ischaemic stroke
than in people who had not had one. Ischaemic strokes occur when the
blood flow to a part of the brain is blocked. They account for 80% of
stroke cases. By testing the DNA of several thousand participants, the
researchers identified a new genetic variant that was associated with
increased risk of a type of ischaemic stroke called a “large vessel
stroke”. In large vessel strokes, one or more of the arteries supplying
blood to the brain become blocked. People can carry up to two copies of
the variant, and the study’s authors estimated that each copy of the
variant a person carried was associated with about a 42% increase in the
odds of a large vessel stroke. However, it is not yet known whether
this genetic variant raises the risk of a stroke, or if it is found near
to another variant that is responsible for the increased risk.
This
well-designed study has identified a new association between a genetic
variation and strokes. However, the study cannot confirm whether the
variation itself causes the increased risk of a stroke. This key issue
will need to be clarified before these findings can contribute to the
development of the new treatments that many newspapers optimistically
predicted.
Where did the story come from? The
study was carried out by researchers from the University of Oxford, St
George’s, University of London, and a number of other UK and
international universities and research institutes. It was funded by The
Wellcome Trust. The study was published in the peer-reviewed scientific journal Nature Genetics.
This
study was covered by a number of newspapers. In general, the coverage
of the research was good, although many news stories focused on its
potential to lead to the development of screening tests and new
treatments. However, there is no guarantee that this research will lead
to such advances. If it does, they are likely to be some way off.
What kind of research was this? This case-control study
aimed to identify genetic factors that are associated with an increased
risk of ischaemic strokes. Ischaemic strokes occur when there is a
blockage of blood flow to part of the brain. This can deprive brain
cells of vital oxygen and nutrients. Around 80% of strokes are
ischaemic. The remainder are haemorrhagic strokes, caused by a blood
vessel rupturing in or around the brain.
To find genetic variants
associated with strokes, the researchers read the DNA sequences of a
group of patients who had had an ischaemic stroke. They compared them to
the sequences of a group of healthy people. Their theory was that
genetic variations that were more common among the stroke group could
potentially be linked to stroke risk. To verify whether the variants
they initially identified in these groups were associated with strokes,
the researchers tested if the same pattern was seen when another group
of stroke patients were compared with another group of healthy
individuals (controls ). This is an accepted method that is used when performing genetic studies of this type.
Although
this was a well-designed study, genetic studies like this one can only
show that a particular genetic variant is associated with a disease.
Further experiments are required to see if the variants identified have a
role in causing strokes, or if they lie close to other genetic variants
that have this effect. What these variants do still needs to be
identified, so media claims that this research could lead to potential
new treatments seem premature.
It is also important to remember
that genetic, medical and lifestyle factors are likely to contribute to a
person’s risk of a stroke. It should not be assumed that a person’s
genetics mean that they will definitely have a stroke. Equally, people
without high-risk genetics may still be at risk of a stroke risk because
of lifestyle factors, such as smoking.
What did the research involve? In
the first phase of the study, researchers recruited 3,548 individuals
who had had an ischaemic stroke (the cases) and 5,972 healthy
individuals (the controls). The researchers looked for genetic variants
that were more common in the stroke group. In a second phase, the
researchers confirmed their findings in a new group of 5,859 cases and
6,281 controls. The new genetic variation they identified was then
re-confirmed in a further 735 cases and 28,583 controls.
What were the basic results? The
researchers identified genetic variants at three locations that have
been associated with different subtypes of ischaemic stroke in previous
studies (near the genes PITX2 and ZFHX3, and on the short arm of
chromosome 9). In addition, they identified a genetic variant at a new
position within the HDAC9 gene, which was associated with a subtype of
ischaemic stroke called large vessel stroke. In large vessel strokes,
one or more of the large arteries supplying blood to the brain become
blocked. This variant in HDAC9 occurs on about 10% of chromosomes in
people in the UK. Humans have two copies of each chromosome, and
therefore we can carry up to two copies of this variant (one on each
chromosome). The researchers calculated that each copy of the variant
that a person possessed was associated with a 42% increase in the odds
of having a large vessel stroke (odds ratio 1.42, 95% confidence interval 1.28 to 1.57 for each copy).
How did the researchers interpret the results? The
researchers concluded that they have “identified a new association with
the HDAC9 gene region in large vessel stroke”. They also stated that
“the mechanism by which variants in the HDAC9 region increase large
vessel stroke risk is not immediately clear.”
Conclusion In
this study, researchers have identified a genetic variant in the HDAC9
gene that is associated with a subtype of ischaemic stroke called a
large vessel stroke. Large vessel strokes occur when one or more of the
arteries supplying blood to the brain become blocked.
In this type
of study, the genetic variants identified as being associated with a
condition are not necessarily the cause of the increase in risk.
Instead, they may lie near another variant that is responsible for the
effect. In order to unlock the role of the HDAC9 gene, researchers will
now need to study it and the region surrounding it more closely, both to
confirm whether the variation in this gene is responsible for the
increase in stroke risk and, if so, how it has this effect.
Genetic,
medical and lifestyle factors are likely to contribute to stroke risk.
In addition, multiple genetic factors may potentially contribute to the
risk. It’s important to note that although having higher-risk genetic
variants increases the risk of having a stroke, it does not guarantee
that a person will have one. Equally, people who do not have any
associated variants can still be at risk of a stroke because of
lifestyles factors such as smoking, drinking and their diet.
This
well-designed study found an association between a new genetic variant
and one type of stroke. As yet, it is not possible to say whether this
finding will lead to the development of new treatments for large vessel
strokes.
Zdroj: web
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Oxford Nanopore introduces DNA \'strand sequencing\' on the high-throughput GridION platform and presents MinION, a sequencer the size of a USB memor
Oxford Nanopore Technologies Ltd. today presented for the
first time DNA sequence data using its novel nanopore 'strand
sequencing' technique and proprietary high performance electronic
devices GridION and MinION. These data were presented by Clive G Brown,
Chief Technology Officer, who outlined the Company's pathway to a
commercial product with highly disruptive features including ultra long
read lengths, high throughput on electronic systems and real-time
sequencing results. Oxford Nanopore intends to commercialise GridION
and MinION directly to customers within 2012.
Oxford Nanopore's GridION system consists of scalable instruments
(nodes) used with consumable cartridges that contain proprietary array
chips for multi-nanopore sensing. Each GridION node and cartridge is
initially designed to deliver tens of Gb of sequence data per 24 hour
period, with the user choosing whether to run for minutes or days
according to the experiment.
Oxford Nanopore will introduce a new model of versatile pricing schemes
designed to deliver a price per base that is as competitive as other
leading systems at launch. Further substantial pricing improvements are
expected with future development to the technology, in particular with
increases in nanopore processing speed and higher density electronic
sensor chips.
Oxford Nanopore has also miniaturised these devices to develop the
MinION; a disposable DNA sequencing device the size of a USB memory
stick whose low cost, portability and ease of use are designed to make
DNA sequencing universally accessible. A single MinION is expected to
retail at less than $900.
"The exquisite science behind nanopore sensing has taken nearly two
decades to reach this point; a truly disruptive single molecule
analysis technique, designed alongside new electronics to be a universal
sequencing system. GridION and MinION are poised to deliver a
completely new range of benefits to researchers and clinicians," said Dr
Gordon Sanghera, CEO of Oxford Nanopore. "Oxford Nanopore is as much
an electronics company as a biotechnology company, and the development
of a high-throughput electronics platform has been essential for us to
design and screen a large number of new candidate nanopores and enzymes.
Our toolbox is customer-ready and we will continue to develop improved
nanopore devices over many years, including ongoing work in solid state
devices."
Summary of presentation
At the Advances in Genome Biology and Technology conference (AGBT), FL, US, Oxford Nanopore presented:
A novel method of DNA 'strand sequencing' that uses an array of
proprietary protein nanopores embedded in a robust polymer membrane.
Each nanopore sequences multiple strands of DNA from solution in
succession, as individual strands are passed through the nanopore by a
proprietary processive enzyme. Base calling is performed by identifying
characteristic electronic signals (disruptions in current through the
nanopore), created by unique combinations of DNA bases as they pass
through a specially engineered region inside the nanopore.DNA and enzyme
are mixed in solution, engage with the nanopore for sequencing and once
the strand has been completed a new strand is loaded into the nanopore
for sequencing.
Genomes that have been sequenced as contiguous reads comprising both
complementary strands of the entire genome. An example was shown of
lamda, a 48kb genome, sequenced as complete fragments, whose sense and
antisense strand total 100 kilobases. Read lengths mirror fragment
sizes in the sample with no exponential loss of processivity.
Accuracy levels competitive with existing market-leading systems were
shown. No deterioration of accuracy is seen throughout the sequencing
of individual strands. A development pathway was presented that is
expected to achieve accuracy exceeding current market-leading platforms
through further design iteration of Oxford Nanopore's custom-made
nanopores.
Oxford Nanopore's GridION platform was presented, consisting of a
scalable network device - a node - designed for use with a consumable
cartridge. Each cartridge is initially designed for real-time sequencing
by 2,000 individual nanopores at any one time. Alternative
configurations with more processing cores will become available in early
2013 containing over 8,000 nanopores.
Nodes may be clustered in a similar way to computing devices, allowing
users to increase the number of nanopore experiments being conducted at
any one time if a faster time-to-result is required. For example, a
20-node installation using an 8,000 nanopore configuration would be
expected to deliver a complete human genome in 15 minutes.
A variety of sample preparation options were presented. No sample
amplification is required and any user-derived sample preparation
resulting in double stranded DNA (dsDNA) in solution is compatible with
the system. With nanopores embedded in robust polymer membranes, dsDNA
can be sensed directly from blood and in some cases with no sample
preparation.
Oxford Nanopore's disruptive "Run Until..." informatics workflow:
Nanopores allow the analysis of data in real time, as the experiment
happens. Each GridION node contains all the computing hardware and
control software required for primary analysis of data as it is streamed
from each nanopore, resulting in full length real-time delivery of
complete reads so that the user can perform secondary analyses as the
experiment progresses. This allows the user to pre-determine an
experimental question and continue the sequencing experiment until
sufficient data have been accumulated to answer the question and move on
to the next experiment.
Oxford Nanopore intends to introduce a new pricing model for its
GridION sequencing system, which moves away from the traditional
instrument price and consumable price. This is designed as a series of
packages that allow the user to tailor a scheme to their budget
structure, whether more flexible with capital or consumable expenditure.
Transparent pricing schemes are designed for online ordering and
fulfilment, with discounts applying to larger packages. Overall the
schemes are designed to deliver a competitive 'price per base' compared
to other systems on the market based on like-for-like user settings.
Further information is available at the Company's website
www.nanoporetech.com. While orders are not yet being taken for the
GridION and MinION systems, interested users may register their interest
at the website.
Zdroj: web
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Mutation linked to 42% rise in stroke risk
A “single genetic mutation can double your risk of stroke”, the Daily Mail has reported.
The newspaper added that scientists hope the discovery could lead to tailored treatments for the condition.
The news is based on research which looked for genetic variations that were more common in people who had had an ischaemic stroke
than in people who had not had one. Ischaemic strokes occur when the
blood flow to a part of the brain is blocked. They account for 80% of
stroke cases. By testing the DNA of several thousand participants, the
researchers identified a new genetic variant that was associated with
increased risk of a type of ischaemic stroke called a “large vessel
stroke”. In large vessel strokes, one or more of the arteries supplying
blood to the brain become blocked. People can carry up to two copies of
the variant, and the study’s authors estimated that each copy of the
variant a person carried was associated with about a 42% increase in the
odds of a large vessel stroke. However, it is not yet known whether
this genetic variant raises the risk of a stroke, or if it is found near
to another variant that is responsible for the increased risk.
This
well-designed study has identified a new association between a genetic
variation and strokes. However, the study cannot confirm whether the
variation itself causes the increased risk of a stroke. This key issue
will need to be clarified before these findings can contribute to the
development of the new treatments that many newspapers optimistically
predicted.
Where did the story come from? The study was
carried out by researchers from the University of Oxford, St George’s,
University of London, and a number of other UK and international
universities and research institutes. It was funded by The Wellcome
Trust. The study was published in the peer-reviewed scientific journal Nature Genetics.
This
study was covered by a number of newspapers. In general, the coverage
of the research was good, although many news stories focused on its
potential to lead to the development of screening tests and new
treatments. However, there is no guarantee that this research will lead
to such advances. If it does, they are likely to be some way off.
What kind of research was this? This case-control study
aimed to identify genetic factors that are associated with an increased
risk of ischaemic strokes. Ischaemic strokes occur when there is a
blockage of blood flow to part of the brain. This can deprive brain
cells of vital oxygen and nutrients. Around 80% of strokes are
ischaemic. The remainder are haemorrhagic strokes, caused by a blood
vessel rupturing in or around the brain.
To find genetic variants
associated with strokes, the researchers read the DNA sequences of a
group of patients who had had an ischaemic stroke. They compared them to
the sequences of a group of healthy people. Their theory was that
genetic variations that were more common among the stroke group could
potentially be linked to stroke risk. To verify whether the variants
they initially identified in these groups were associated with strokes,
the researchers tested if the same pattern was seen when another group
of stroke patients were compared with another group of healthy
individuals (controls ). This is an accepted method that is used when performing genetic studies of this type.
Although
this was a well-designed study, genetic studies like this one can only
show that a particular genetic variant is associated with a disease.
Further experiments are required to see if the variants identified have a
role in causing strokes, or if they lie close to other genetic variants
that have this effect. What these variants do still needs to be
identified, so media claims that this research could lead to potential
new treatments seem premature.
It is also important to remember
that genetic, medical and lifestyle factors are likely to contribute to a
person’s risk of a stroke. It should not be assumed that a person’s
genetics mean that they will definitely have a stroke. Equally, people
without high-risk genetics may still be at risk of a stroke risk because
of lifestyle factors, such as smoking.
What did the research involve? In
the first phase of the study, researchers recruited 3,548 individuals
who had had an ischaemic stroke (the cases) and 5,972 healthy
individuals (the controls). The researchers looked for genetic variants
that were more common in the stroke group. In a second phase, the
researchers confirmed their findings in a new group of 5,859 cases and
6,281 controls. The new genetic variation they identified was then
re-confirmed in a further 735 cases and 28,583 controls.
What were the basic results? The
researchers identified genetic variants at three locations that have
been associated with different subtypes of ischaemic stroke in previous
studies (near the genes PITX2 and ZFHX3, and on the short arm of
chromosome 9). In addition, they identified a genetic variant at a new
position within the HDAC9 gene, which was associated with a subtype of
ischaemic stroke called large vessel stroke. In large vessel strokes,
one or more of the large arteries supplying blood to the brain become
blocked. This variant in HDAC9 occurs on about 10% of chromosomes in
people in the UK. Humans have two copies of each chromosome, and
therefore we can carry up to two copies of this variant (one on each
chromosome). The researchers calculated that each copy of the variant
that a person possessed was associated with a 42% increase in the odds
of having a large vessel stroke (odds ratio 1.42, 95% confidence interval 1.28 to 1.57 for each copy).
How did the researchers interpret the results? The
researchers concluded that they have “identified a new association with
the HDAC9 gene region in large vessel stroke”. They also stated that
“the mechanism by which variants in the HDAC9 region increase large
vessel stroke risk is not immediately clear.”
Conclusion In
this study, researchers have identified a genetic variant in the HDAC9
gene that is associated with a subtype of ischaemic stroke called a
large vessel stroke. Large vessel strokes occur when one or more of the
arteries supplying blood to the brain become blocked.
In this type
of study, the genetic variants identified as being associated with a
condition are not necessarily the cause of the increase in risk.
Instead, they may lie near another variant that is responsible for the
effect. In order to unlock the role of the HDAC9 gene, researchers will
now need to study it and the region surrounding it more closely, both to
confirm whether the variation in this gene is responsible for the
increase in stroke risk and, if so, how it has this effect.
Genetic,
medical and lifestyle factors are likely to contribute to stroke risk.
In addition, multiple genetic factors may potentially contribute to the
risk. It’s important to note that although having higher-risk genetic
variants increases the risk of having a stroke, it does not guarantee
that a person will have one. Equally, people who do not have any
associated variants can still be at risk of a stroke because of
lifestyles factors such as smoking, drinking and their diet.
This
well-designed study found an association between a new genetic variant
and one type of stroke. As yet, it is not possible to say whether this
finding will lead to the development of new treatments for large vessel
strokes.
Zdroj: web
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Lipid Genetics Linked to Type 2 Diabetes Risk
Individuals who are genetically predisposed to have low levels
of high-density lipoprotein cholesterol or high levels of triglycerides
have an increased risk of developing type 2 diabetes, according to a
study published online Feb. 7 in Diabetes .
MONDAY, Feb. 13 (HealthDay News) -- Individuals who are
genetically predisposed to have low levels of high-density lipoprotein
(HDL) cholesterol or high levels of triglycerides have an increased risk
of developing type 2 diabetes, according to a study published online
Feb. 7 in Diabetes .
To examine the association between genetic predisposition to
dyslipidemia (based on established loci for blood lipids) and the risk
of type 2 diabetes, Qibin Qi, Ph.D., from the Harvard School of Public
Health in Boston, and colleagues analyzed data from 2,447 patients with
type 2 diabetes from the Nurses' Health Study, and 3,052 control
subjects free of diabetes from the Health Professionals Follow-up Study.
Based on genotype scores for low-density lipoprotein (LDL)
cholesterol, HDL cholesterol, and triglycerides, the researchers found
that only the HDL cholesterol and triglycerides scores were linearly
associated with an increased risk of type 2 diabetes. For each point of
the HDL cholesterol genotype score, there was a 3 percent increase in
the risk of developing type 2 diabetes, and for each point on the
triglyceride genotype score, the increase was 2 percent. Comparing the
highest and lowest quartiles of genotype scores, the odds ratios for
type 2 diabetes were 1.39 for HDL cholesterol and 1.19 for
triglycerides.
"In conclusion, genetic predisposition to low HDL cholesterol or high
triglycerides is related to elevated type 2 diabetes risk," Qi and
colleagues write.
Zdroj: web
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The Genetic Outlier
in January 1999, an effervescent 28-year-old woman named Shonnie Medina died of breast cancer in the remote southern Colorado valley that had long been home to her family. The same disease had killed many of Medina's ancestors; soon after, it would claim the lives of her sister, aunt and several cousins. Although one can't be certain, it is likely that all of their cancers, each and every one, were due to a mutation known as BRCA1.185delAG. The name is scientific shorthand for an inherited problem in the Medinas' DNA: the deletion of two links in the long chain of chemical "bases" that makes up the gene BRCA1. BRCA1 directs the production of a substance that helps eliminate the random cellular mishaps that lead, over time, to breast and ovarian cancer. The deletion of those two links doesn't directly cause cancer; instead, it incapacitates the gene, making the body less able to prevent the disease. Because the molecular mistakes that BRCA1 fixes are common, half or more of the women with the defective gene will develop breast or ovarian cancer. Worse, they are likely to develop it early, and in an especially deadly form. In the mid-1990s, researchers determined that BRCA1.185delAG had originated as much as 2,500 years ago, in biblical Palestine. The type of cancer that felled Shonnie and the other Medina women is thus tightly linked with Jewish ancestry—surprising, because the Medinas, like their neighbors, are Hispanos, descendants of Spanish colonists in the areas that the U.S. seized from Mexico. What did it mean that the Medinas, who considered themselves of Spanish and Indian ancestry, had "Jewish" DNA ? If their ancestors were Spanish Jews, as seems possible, did that suggest that they were somehow Jewish? On a larger scale, what happens when one ties genetics—blood, in other words—to culture and identity? As Jeff Wheelwright recounts in his always intriguing, occasionally frustrating "The Wandering Gene and the Indian Princess," Shonnie Medina's brief life was a small part of a recently revealed, centuries-old snarl of race, culture and creed. As humankind becomes more technologically sophisticated, identity becomes both more fluid and more fixed. People can more readily concoct their own personas, mixing and matching elements they find on the Internet; meanwhile, genetics pins us ever tighter to our own heredity. The resultant confusion spills over into a host of subjects: ethnic profiling, affirmative action, religious identity tests, the complex of issues summed up in Charles Murray and Richard Herrnstein's "The Bell Curve." All reliably provoke temper tantrums, red-faced accusations and wounded feelings. Conservatives are more often lambasted for their views than liberals, but liberals are no less prone to the fantastic and illogical. Mr. Wheelwright, the former science editor of Life magazine, tiptoes with impressive agility through the minefield; this is one of the rare books on this vexed subject that get the technical stuff right—and that understand that people make what they will of scientific findings. Jews, historically an insular group, were a ready subject for the new discipline of human genetics, as Mr. Wheelwright recounts. After the 1970s, when DNA screening for harmful inherited conditions like Tay-Sachs disease, Gaucher disease and cystic fibrosis became available, Jews quickly embraced it. More important, and perhaps more ominous, genetics was used to establish Jewish identity. Partly because they possess certain snippets of DNA , the Lemba of southern Africa have been widely accepted as Jewish. Indeed, the findings have been trumpeted as "proof" that Zionism and Israel are not racist. Meanwhile, the claim of the Beta Israel and Falash Mura to Jewish identity—120,000 of whom have fled Ethiopia's wars since the late 1970s to live in Israel—has been undermined because many lack those DNA snippets. Inevitably, this has been touted as "proof" that Zionism and Israel are racist. Such controversies are not restricted to Jews. Before Columbus, Native American groups determined membership by culture. If people, say, spoke the Huron language, embraced Huron custom and creed, and were loyal to the tribe, they were accepted as members of the Huron. In the late 18th century, it has been estimated, about three quarters of the Iroquois had not been born into Iroquois families but had been adopted as captives or runaways. Despite this tradition, several Indian groups, notably the Seminole, have taken to expelling tribal members with insufficiently "Indian" DNA—giving contemporary, European-style biology priority over traditional indigenous views. Mr. Wheelwright concentrates on the finding that Hispanos like the Medinas have not only BRCA1.185delAG—"Jewish" DNA—but some possibly Jewish customs, such as lighting candles on the Sabbath, suggesting that they may be descended from Jews who pretended to convert to Christianity to escape the Inquisition but who continued to practice their faith in secret. Crypto-Jews in Colorado, hidden for centuries!—such claims are catnip to journalists because they make the world more interesting. Nonetheless, they may be true, at least in part. Many of the first Europeans in the U.S. Southwest indeed were conversos, Jews forced into Catholicism. Even if they wholeheartedly took up their new faith, they surely carried with them, as all people do, aspects of their ancestors, including Jewish customs and perhaps faith. The notion has led to a boomlet of people claiming, Madonna-style, to have found their spiritual roots in ancient Palestine; to bouts of confusion in Southwestern churches, which find some of their congregations claiming to be Jewish; and to a small academic rumpus over whether folk customs and memories can be used as proof of ancestry. The data presented by the disputants are first shaky (some genetic indicators) and then shakier (funny marks on old graves, odd customs with candles). By the end of Mr. Wheelwright's book, we're listening to a Hispano rancher tell a hippyish rebbe how his grandfather "went overboard with cleanliness," said fastidiousness being evidence for suppressed Judaism. ("Nobody would admit there was any Jewish in them, he said.") To which your meticulous reviewer, the product of a long line of Episcopalian ministers, can only say, "Oy." Rather than being confined by her Judeo-Hispano-Indian roots, Shonnie Medina joined the Jehovah's Witnesses, a religious group founded by Scots-Irish Protestants that refuses blood transfusions, denounces the Pledge of Allegiance and rejects the symbol of the Cross (Christ, Witnesses believe, died on a tree). The strictures of Medina's new faith made cancer surgery impossible, because she wouldn't accept the necessary transfusions; vain about her beauty, she couldn't bear the prospect of a mastectomy. Instead she put her hopes in yet another spiritual tradition—homeopathy, popularized by Germans in the 19th century. When that failed, she went to a clinic in Tijuana that dispenses, in a cloud of New Age hokum, herbal medicines of a type banned in the U.S. since 1960. The results were as one would expect. Mr. Wheelwright evokes Medina's choices with great sympathy; he helps the reader see why a course of action that looks self-destructive from the outside might have been logical, even necessary, for her. To my taste, he is sometimes less successful in guiding the reader through his story. I wondered why, for instance, Mr. Wheelwright waited to explain how DNA works until halfway through the book. About one long-delayed anecdote he remarks, "Well, before finally hearing about Bea, there's an additional incident to relate." Still, the author is onto something here. As William Blake saw the world in a grain of sand, Mr. Wheelwright has seen in Shonnie Medina's brief life the tangle in which we are enmeshed, as we learn ever more about ourselves and are ever less clear about what to do with the knowledge.
Zdroj: web
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New prenatal genetic test is more powerful
Testing a developing fetus' DNA via
chromosomal microarray gives more information about disorders than
standard prenatal testing, U.S. researchers say.
The researchers, led by Dr. Ronald Wapner, director of reproductive
genetics at NewYork-Presbyterian Hospital/Columbia University Medical
Center and of Columbia University College of Physicians and Surgeons,
found that in women having routine prenatal diagnosis, chromosomal
microarray detected additional genetic abnormalities in about 1-in-70
fetal samples that had a normal karyotype.
When a birth defect was imaged by ultrasound, chromosomal microarray
found additional important genetic information in 6 percent of cases and
these results suggested that chromosomal microarray may soon replace
karyotyping for prenatal testing, Wapner said.
"Why would anyone want to continue to use the standard method, which
gives only part of the answer?" Wapner asked. "However, we will have to
carefully transition this information into clinical practice-to educate
physicians and patients, develop guidelines for its use, and learn how
to best use it to improve care."
Wapner led the 34-center study funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
The results of the 4,000-plus-participant clinical study were
presented at the 32nd annual meeting of the Society for Maternal-Fetal
Medicine in Dallas. The study was recently published in the American
Journal of Obstetrics & Gynecology
Zdroj: web
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Genetic risks for type 2 diabetes span multiple ethnicities
A recent large and comprehensive analysis of 50,000 genetic variants
across 2,000 genes linked to cardiovascular and metabolic function has
identified four genes associated with type 2 diabetes (T2D) and six
independent disease-associated variants at previously known loci. The
findings, which provide valuable insight into the genetic risk for T2D
across multiple ethnicities, add to the growing list of genetic variants
that affect the risk of developing T2D and could pave the way for
identification of valuable drug targets. The research will be published
by Cell Press on February 9th in The American Journal of Human Genetics , the official journal of the American Society of Human Genetics.
Multiple environmental and genetic factors are linked with T2D,
which is the most common form of diabetes. "Together, known T2D genetic
variants explain only about 10% of the genetic variance, indicating that
additional genetic factors are likely to contribute to disease risk,"
explains senior co-author Dr. Brendan J. Keating, from The Children's
Hospital of Philadelphia. "Further, previous studies have been based
almost exclusively on individuals of European ancestry, and genetic
contributors to T2D are less well understood in non-European
populations. An important first step towards understanding genetic risk
across populations is to establish whether known T2D-associated genes
span ethnicities or are population specific."
Dr. Keating, senior co-author Dr. Richa Saxena, from Massachusetts
General Hospital and Harvard Medical School, and a large international
cohort of colleagues undertook an ambitious genetic screening study to
gain a better understanding of genetic variants associated with T2D.
Their analysis, the largest T2D genomics study conducted to date,
included 39 multiethnic T2D association studies representing more than
17,000 cases of T2D and 70,000 controls and was designed to assess the
impact of genetic variants across multiple ethnicities.
"As a result of our large-scale genetic analysis, we uncovered
previously unknown European and multiethnic genetic variants and
confirmed that, together, known genetic risk factors influence T2D risk
in multiethnic populations, including African-Americans, Hispanics, and
Asians," concludes Dr. Saxena. "Several additional signals were of
borderline significance. Overall, our results demonstrate that this type
of large multiethnic genome-wide screening study should lead to
identification of additional T2D genetic variants relevant to multiple
ethnic groups. Further, identification of additional genes associated
with T2D may guide strategies for developing new therapeutics."
Zdroj: web
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Male Genes May Explain Higher Heart Disease Risk
Although heart disease is the leading killer of women as well as of men,
two heart disease patients out of every three are male, and heart
disease strikes men 10 to 15 years earlier than it does women. No one
really knows why. Now, a new study reports that part of the answer may lie on the Y chromosome, the one chromosome unique to men. In the study, published on Wednesday in The Lancet, researchers found that nearly all British men have one of two variants of a cluster of genes on their Y chromosome. Those with one of the variants had a 50 percent increased risk of heart disease compared with men with the other variant. This risk was independent of traditional factors like cholesterol, smoking and diabetes. The study needs to be replicated, researchers say, and while it raises intriguing hypotheses, it is not definitive. The researchers also do not yet know which individual genes in the cluster are responsible for the increased risk, nor do they know why the genes have this effect. And the study, said its lead author, Dr. Maciej Tomaszewski of the University of Leicester, does not completely explain the male disadvantage in heart disease. But Virginia M. Miller, a heart disease researcher at the Mayo Clinic in Rochester, Minn., who wrote an editorial that accompanied the paper, said in an interview that the work “puts a whole different perspective on some risk factors for heart disease in men.” Everyone knows men who did all the wrong things — ignored their cholesterol levels, smoked — and yet were spared heart disease, Dr. Miller said. And everyone knows men who were careful about their diet, controlled their cholesterol levels and blood pressure and did not smoke, yet died young from heart attacks. The message of the new study, Dr. Miller said, was that for some of those unlucky men, “yes indeed, they did have inheritable factors that independently caused death.” And when a screening test is developed to find those Y chromosome gene clusters and researchers have a better understanding of how they act, it may be possible to protect some of them from having heart attacks. Dr. Tomaszewski and his colleagues found the Y chromosome gene association by looking at men in two large British heart disease studies. He said he and his colleagues were surprised by the magnitude of increase in risk for men with one of two genetic clusters. Dr. Daniel J. Rader, a heart disease researcher at the University of Pennsylvania, said it was also possible that simply having a Y chromosome instead of two X chromosomes, as women have, increased heart disease risk. The extra X could be protective. Dr. Sekar Kathiresan, director of preventive cardiology at Massachusetts General Hospital, said it was strange that there had been almost no study of the Y chromosome’s effect on heart disease. Although the reasons were technical, having to do with the way gene searches were done, ignoring the Y, he said, “was a little bit of an oversight.” Heart disease researchers have generally ignored the role of the Y chromosome, assuming it was mostly involved in determining maleness, Dr. Tomaszewski said. He suggested the cluster of genes on the Y chromosome of the men with lower risk may help control inflammation, a process that is part of the formation of atherosclerotic plaques. Others were less convinced. “A lot more work needs to be done” on the gene cluster, Dr. Rader said. Dr Kathiresan said the association between the gene cluster and heart disease risk needed to be confirmed.
Zdroj: The New York Times
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VCU Study: Antisocial Personality Disorder Influenced by Two Areas of Genetic Risk
Virginia Commonwealth University researchers have identified
that genetic risk factors for antisocial personality disorder are due to
two distinct genetic dimensions of risk, as outlined by the DSM-IV
criteria, and not solely by one genetic factor.
The Diagnostic and Statistical Manual of Mental Disorders
fourth edition, or DSM-IV, is a manual published by the American
Psychiatric Association that categorizes all mental health disorders
for children and adults. Researchers have not examined the factor
structure of the DSM-IV criteria for antisocial personality disorder
until now.
In the study, published online today in the February issue of
Biological Psychiatry, using a twin study model, researchers conducted
an in-depth analysis of the antisocial personality disorder criteria of
the DSM-IV. Antisocial personality disorder is a psychiatric disorder
characterized by a person’s long-term pattern of manipulation or
exploitation of those around them.
Read the journal’s release here .
“The key finding of this report is that genetic risk factors for
antisocial personality disorder cannot be captured by just one
dimension,” said first author Kenneth Kendler, M.D., director of the VCU
Virginia Institute for Psychiatric and Behavioral Genetics.
“You need at least two independent sets of risk genes to explain the underlying nature of this disorder,” he said.
According to Kendler, the team assessed adult twins from the Virginia
Twin Study of Psychiatric and Substance Use Disorders by a self-report
questionnaire. Next, a multivariate twin analysis was conducted to
test for the presence of genetic and environmental factors on the
criteria. Once the dimensions were identified, the team evaluated its
validity.
Kendler collaborated with Steven H. Aggen, Ph.D., research associate
at the VCU Virginia Institute for Psychiatric and Behavioral Genetics,
and Christopher J. Patrick, Ph.D., a research clinical psychologist at
Florida State University.
The work was supported in part from the National Institutes of Health.
Zdroj: web
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Gene therapy proves effective for hemophilia B
A single
treatment with gene therapy, an experimental technique for fixing faulty
genes, has been shown to boost output of a vital blood clotting factor,
possibly offering a long-term solution for people with hemophilia B.
Researchers said the same
technology was also being studied as a treatment for hemophilia A, the
far more common type of the inherited bleeding disorder.
"It
is a technique for potentially permanently curing patients," said Dr.
Charles Abrams, American Society of Hematology secretary and associate
chief of hematology/oncology at the University of Pennsylvania in
Philadelphia.
Both safety and
efficacy have held back the field of gene therapy . One experiment cured
two French boys with a rare immune disorder but gave them leukemia in
2002, and an Arizona teenager died in a 1999 gene therapy experiment.
The
approach used by researchers at the University College London Cancer
Institute and St. Jude Children's Research Hospital in Memphis,
Tennessee, involved the use of a novel viral "vector," designed to
target the liver specifically.
The
strategy involves replacing the defective gene that causes the bleeding
disorder with a correct version delivered via the virus to the patient's
liver cells - the only cells in the body capable of producing certain
clotting factors missing or deficient in people with hemophilia.
The
factors are numbered using Roman numerals. The two main forms of the
disease are hemophilia A, caused by a lack of clotting factor VIII, and
hemophilia B, caused by a lack of clotting factor IX.
Researchers
have so far treated six men with severe hemophilia B who were producing
clotting factor IX at less than 1 percent of normal levels. The general
goal of current treatment with recombinant factor IX is to achieve
factor levels greater than 1 percent of normal.
Four
of the six trial participants have stopped routine treatment and remain
free of spontaneous bleeding. The other two have increased the interval
between factor infusions to once every 10 days to two weeks from two to
three times a week, said Dr. Andrew Davidoff, chairman of the
department of surgery at St. Jude's and co-author of the study.
HIGH COST FOR CURRENT TREATMENT
Frequent
treatments with manufactured factor IX, known as recombinant factor
concentrates, can cost hundreds of thousands of dollars a year, making
hemophilia a tempting target for gene therapy.
The
trial "is truly a landmark study," Dr. Katherine Ponder, hematology and
oncology professor at Washington University in St. Louis, said in a New
England Journal of Medicine editorial.
"If
further studies determine that this approach is safe, it may replace
the cumbersome and expensive protein therapy currently used for patients
with hemophilia B," she wrote.
The
trial results were published in the NEJM and reported on Saturday at a
meeting of the American Society of Hematology in San Diego.
The six trial subjects were broken into three groups with each group receiving a different concentration of new genes.
Factor
IX levels in the first subject have remained at 2 percent for nearly
two years, while the two patients treated with the highest dose have
seen FIX levels rise to between 3 and 12 percent, researchers said.
One
high-dose subject developed elevated levels of transaminases, an
indicator of possible liver damage, and another had a slight increase in
liver enzymes. Both cases were resolved with steroids, the researchers
said.
Plans are to treat more
patients with the highest dose used so far, and if research continues to
succeed, the treatment could be widely available "in the next five
years or so," said Dr. Amit Nathwani, co-lead study author of the
Department of Hematology at UCL Cancer Institute in London.
He also said the team was working to use the technique for treating hemophilia A.
ISI
Group analyst Mark Schoenebaum said the gene therapy could pose big
competition for companies such as Biogen Idec that are producing
recombinant factor concentrates.
"This
clearly presents a curveball to our (and much of Wall Street's)
assumptions around the future of the hemophilia market," he said in an
email to investors.
The analyst
said estimated sales of the hemophilia factors accounted for between $10
and $17 of his $125 price target for shares of Biogen, which closed at
$112.95 on Friday.
People with
hemophilia bleed more following trauma than people without the disease,
and those with severe disease may bleed spontaneously. Since the gene is
carried on the X chromosome, hemophilia is almost exclusively a disease
of men.
But women can pass the gene to their offspring.
Hemophilia
has often been called the "Royal Disease" since it was carried by
Britain's Queen Victoria and affected many of the royal families of
Europe.
Hemophilia B is much less
common than hemophilia A. About one in five hemophilia patients has
hemophilia B, according to the National Institutes of Health.
The global market for Factor VIII products is about $5 billion, while the market for Factor IX is worth about $1 billion.
Worldwide, about one in 5,000 men is born with hemophilia A and 1 in 25,000 men is born with hemophilia B each year.
Zdroj: Reuters.com
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Mikrobiální chemická továrna
Výzkumníci z americké Riceovy Univerzity objevili
způsob, jak přinutit známé bakterie Escherichia coli k rychlé produkci
velkého množství průmyslově důležitých chemických látek.
S těmito bakteriemi
se v běžném životě setkáváme velmi často. Žijí totiž v tlustém střevě
mnoha teplokrevných živočichů. Jsou také jedním z nejdůležitějších
zástupců naší střevní mikroflóry a jejich přítomnost je nezbytná pro
správný průběh trávicích procesů ve střevě.
Inženýři z Riceovy Univerzity Ramon Gonzalez a Clementina
Dellomonaco pomocí speciálních genetických manipulací dosáhli toho, že
tyto bakterie místo svého normálního metabolismu začaly fungovat jaksi
"metabolicky obráceně". Stačila k tomu změna asi dvanácti genů. V
normálním přirozeném režimu bakterie Escherichia coli vykonávají tzv. beta oxidační
cyklus. V rámci tohoto řetězce chemických reakcí zpracovávají
uhlovodíkové i jiné složité organické látky, např. mastné kyseliny s
dlouhými řetězci, a výsledkem jsou biologicky aktivní jednodušší cukry.
Inženýrům se však povedlo vyrobit geneticky upravené bakterie , u
kterých probíhá tento metabolický řetězec obráceně. Nové baktérie cukry
konzumují, stačí jim někdy dokonce jen glukóza a málo minerálních
solí, a pak na objednávku vyrábějí látku, kterou lze použít jako
náhradní biopalivo ve spalovacích motorech nebo jako náhradní surovinu
pro chemický průmysl. Konkrétně jde o sloučeninu zvanou butanol.
Modifikované bakterie zvládly butanol vyrábět desetkrát rychleji než
kterékoliv jiné do této doby známé organismy.
Základ molekuly butanolu se skládá ze čtyř atomů uhlíku,
butanol má tedy relativně krátký řetězec. Původně zmíněné mastné
kyseliny mívají kolem deseti atomů uhlíku nebo více, ale jejich zpětná
výroba z cukrů je v tomto případě energeticky velmi náročná. Nicméně ani
výroba mastných kyselin obecně není vyloučena, ba naopak. Podle
výzkumníků z Riceovy Univerzity lze typ genetické manipulace obměňovat v
rámci širokého množství variant, a tak získat různé druhy umělých
baktérií, které pak volitelně vyrábějí i mnohem složitější chemické
sloučeniny. A některé i s velmi dlouhými molekulárními řetězci.
Zdroj: ČRo
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Scientists find new ovarian cancer gene
Women who carry a
faulty copy of a gene called RAD51D have an almost one in 11 chance of
developing ovarian cancer, scientists said on Sunday in a finding they
called the most significant ovarian cancer gene discovery for more than
10 years.
Tests to identify those at
highest risk are expected to be available within a few years, according
to Cancer Research UK, and may lead some women to decide to have their
ovaries removed in order to beat the disease.
The finding should also speed the search for new drugs.
Laboratory
experiments already suggest that cells with faulty RAD51D are sensitive
to PARP inhibitors - a new class of drugs designed to target cancers
caused by faults in two known breast and ovarian cancer genes, BRCA1 and
BRCA2.
Several large drugmakers,
including Abbott , Merck, Pfizer , Sanofi-Aventis and AstraZeneca , are
developing PARP inhibitors, which work by blocking DNA repair mechanisms
in cancer cells, stalling the cell cycle and leading to cell death.
Data
released in May showed that one of these, AstraZeneca's olaparib, was
able to slow the progression of ovarian cancer in a mid-stage clinical
trial.
For the latest study,
researchers from Britain's Institute of Cancer Research compared the DNA
of women from 911 families with ovarian and breast cancer to DNA from a
control group of more than 10,000 people from the general population.
They found eight faults in the RAD51D gene in women with cancer, compared with only one in the control group.
"Women
with a fault in the RAD51D gene have a one in 11 chance of developing
ovarian cancer," said Nazneen Rahman of the Institute of Cancer Research
and The Royal Marsden in London, who led the study and published its
findings in the journal Nature Genetics.
Ovarian cancer can remain hidden for a long time and thus is often not discovered until it is advanced.
An
estimated 230,000 women worldwide are diagnosed with ovarian cancer
each year. Most are not diagnosed before the cancer has spread, and up
to 70 percent of them die within five years.
Because
of this, Rahman said, women with the faulty gene may decide their best
option is to have their ovaries removed after they have children -
particularly if they have already seen other family members die of the
disease.
Speaking to Reuters in a
telephone interview she said the identification of RAD51D pointed to
PARP inhibitors as a new class of drugs that might offer fresh hope.
Initial tests in the laboratory found that cells with faulty RAD51D were
highly sensitive to this class of drugs.
"PARP
inhibitors work because they were designed to target DNA repair
pathways," she said. "They haven't been used in patients in that context
yet but we would predict they would behave in the same way."
Zdroj: Reuters.com
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Breast cancer gene patent reinstated
How's this for a brain teaser: gene patents scrapped
last year on the grounds that they were based on natural molecules were
last week reinstated on the grounds that the molecules are, after all,
unnatural. The development is the latest twist in a dispute over patents
on the BRCA1 and BRCA2 gene variants that raise the risk of breast cancer.
The result will likely be welcomed in
the biotech industry, which has already patented 4000 human genes, but
civil liberties groups are less than impressed.
In a ruling last March , the US District Court for the Southern District of New York declared the patents invalid because they describe genes found in nature, which cannot be patented as they are not inventions.
Last week, the Court of Appeals for the Federal Circuit reached the opposite conclusion . It decided that the BRCA genes patented by Myriad Genetics
of Salt Lake City, Utah, differ from their natural counterparts by
omitting non-coding "junk" regions that are present in the human body.
"The molecules as claimed do not exist in nature," says the judgment.
The American Civil Liberties Union
and the Public Patent Foundation, which originally brought the case in
2009, may yet appeal. "Human DNA is not a manufactured invention, but a
natural entity like air or water," says Chris Hansen, a lawyer with the
ACLU.
Patents on the same two genes were rescinded by the European Patent Office in 2004.
Zdroj: New Scientist
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Miniature 'knot lab' could help untangle DNA mystery
The first microscopic knots have been created inside a liquid crystal. This miniature "knot laboratory" could help mathematicians study the intricacies of knot theory and even help us understand how DNA is unravelled.
While knots may conjure up images of sailors and boy scouts, their potential for complexity poses problems throughout science, from the more esoteric reaches of mathematics to biology. For instance, biologists know that enzymes untie double-stranded DNA so that proteins can be produced. "But it's still not very clear how this actually works," says Uroš Tkalec of the Jožef Stefan Institute in Ljubljana, Slovenia.
To see if they could create microscopic knots, he and his colleagues turned to the kind of liquid crystal used in laptop displays and TVs. These materials flow like fluids but their constituent molecules are aligned in the same direction, more like a solid crystal.
The researchers added silica particles about 4.72 micrometres across to a liquid crystal and sandwiched the mixture between two glass plates.
Star of David
Each silica particle was coated with a surfactant, making its surface hydrophobic. This disrupted the crystal's highly ordered structure – any liquid crystal molecule adjacent to a silica particle aligned itself perpendicular to the curved surface of the particle and these "disordered" molecules formed a three-dimensional Saturn's ring around the surface. "It's visible like a black ring around the particle," says Tkalec.
When the team trapped the loops with a laser and brought them close together, they immediately joined up to form a bigger, twisted loop around both the particles. A similar thing happened with three particles. By bringing just the right combination of twisted loops into contact, these arrays could be made to unknot and then re-knot to form loops that aren't just twisted, but are intertwined.
And by using a series of moves known as Reidemeister moves, which define how one knot can be turned into another equivalent knot, the team identified a range of well-known knots, from the simple Hopf link (two interlocked loops) to the Star of David to Borromean rings (see diagram ). "[With 16 particles] you can achieve up to 80 topologically different structures," says Tkalec.
Topological bond
Randall Kamien , an expert on liquid crystals at the University of Pennsylvania in Philadelphia, says, "[The work] opens up the possibility of doing experimental knot theory." He imagines robotic machines manipulating arrays of loops inside a liquid crystal. "In principle, you can make a grid of 10,000 knots and study them in a data-intensive way," he says.
Besides exploring the more esoteric extremes of knot theory, there may be practical applications, for instance, for understanding DNA knotting. "We don't have other systems where we can control knot formation on microscopic scale. [Now], you have a fully controllable reconfiguration of arbitrary microscopic knots and links," says Tkalec.
The technique might also lead to a new kind of biomarker. If biologists want to study a given protein, they usually "tag" it with a marker molecule, which binds itself to the protein, potentially altering its properties. But what if you created a loop of a biomarker material around a protein that could be tracked under a microscope? "Imagine [tying] little things, or tracers, onto big molecules," says Kamien. "It's a topological bond, not a chemical bond."
Zdroj: New Scientist
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Fast DNA sequencing with a graphene-based nanochannel device
Devices in which a single strand of DNA is threaded through a nanopore could be used to efficiently sequence DNA. However, various issues will have to be resolved to make this approach practical, including controlling the DNA translocation rate, suppressing stochastic nucleobase motions, and resolving the signal overlap between different nucleobases. Here, we demonstrate theoretically the feasibility of DNA sequencing using a fluidic nanochannel functionalized with a graphene nanoribbon. This approach involves deciphering the changes that occur in the conductance of the nanoribbon as a result of its interactions with the nucleobases via π–π stacking. We show that as a DNA strand passes through the nanochannel, the distinct conductance characteristics of the nanoribbon (calculated using a method based on density functional theory coupled to non-equilibrium Green function theory) allow the different nucleobases to be distinguished using a data-mining technique and a two-dimensional transient autocorrelation analysis. This fast and reliable DNA sequencing device should be experimentally feasible in the near future. Kim and his team designed a hypothetical nanochannel device that radically improves sequencing accuracy by introducing graphene nanoribbons — narrow strips of carbon just one atom thick. In this model (see image), a DNA strand flows down a silicon nitride nanochannel and passes beneath a narrow graphene nanoribbon bridge. Because graphene and nucleotides share similar benzene-like rings, attractive aromatic stacking forces can force the DNA to lie flat in the channel, preventing the random movements of the DNA strand that have previously impeded performance. The simulations also showed that graphene’s unique electronic properties allow for highly sensitive nucleotide detection. Electrons usually move with zero resistance through the graphene framework, but in the presence of DNA strands, the conductance of the graphene nanoribbon dips sharply following a pattern specific to each nucleotide. The researchers developed a sophisticated algorithm that turned the time-dependent conductance of the device into a precise, automatic read-out of the DNA sequence. Importantly, the proposed device can be built using existing clean-room protocols, meaning that it may soon be in the hands of researchers. “Identifying a single nucleotide on a graphene nanoribbon would be a significant first step in this direction,” says Kim.
Zdroj: web
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Fast DNA sequencing with a graphene-based nanochannel device
Devices in which a single strand of DNA is threaded through a nanopore could be used to efficiently sequence DNA. However, various issues will have to be resolved to make this approach practical, including controlling the DNA translocation rate, suppressing stochastic nucleobase motions, and resolving the signal overlap between different nucleobases. Here, we demonstrate theoretically the feasibility of DNA sequencing using a fluidic nanochannel functionalized with a graphene nanoribbon. This approach involves deciphering the changes that occur in the conductance of the nanoribbon as a result of its interactions with the nucleobases via π–π stacking. We show that as a DNA strand passes through the nanochannel, the distinct conductance characteristics of the nanoribbon (calculated using a method based on density functional theory coupled to non-equilibrium Green function theory) allow the different nucleobases to be distinguished using a data-mining technique and a two-dimensional transient autocorrelation analysis. This fast and reliable DNA sequencing device should be experimentally feasible in the near future. Kim and his team designed a hypothetical nanochannel device that radically improves sequencing accuracy by introducing graphene nanoribbons — narrow strips of carbon just one atom thick. In this model (see image), a DNA strand flows down a silicon nitride nanochannel and passes beneath a narrow graphene nanoribbon bridge. Because graphene and nucleotides share similar benzene-like rings, attractive aromatic stacking forces can force the DNA to lie flat in the channel, preventing the random movements of the DNA strand that have previously impeded performance. The simulations also showed that graphene’s unique electronic properties allow for highly sensitive nucleotide detection. Electrons usually move with zero resistance through the graphene framework, but in the presence of DNA strands, the conductance of the graphene nanoribbon dips sharply following a pattern specific to each nucleotide. The researchers developed a sophisticated algorithm that turned the time-dependent conductance of the device into a precise, automatic read-out of the DNA sequence. Importantly, the proposed device can be built using existing clean-room protocols, meaning that it may soon be in the hands of researchers. “Identifying a single nucleotide on a graphene nanoribbon would be a significant first step in this direction,” says Kim.
Zdroj: web
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Telomere Nobelist: Selling a 'biological age' test
Elizabeth Blackburn is launching a commercial genetic test that measures DNA markers of ageing – what can we learn from it?
Your test measures telomere shortening, a marker of biological ageing . What can this tell us? Telomeres
are stretches of DNA at the ends of chromosomes that protect them
against degradation. Checking your telomere length is a bit like
weighing yourself: you get this single number which depends on a lot of
factors. Telomere length gives a sense of your underlying health. We see
telomere shortening in diseases of ageing - like heart disease and
cancer.
What evidence is there to support health predictions based on telomere length? In
2004, results from a study that I worked on with colleagues at the
University of California, San Francisco, linked chronic stress to
shortening of telomeres. Chronic stress is also associated with a higher
risk of heart disease. Bone marrow failure is also associated with
short telomeres. If a test showed you had telomere shortening, it would
be a red flag suggesting you should take a look at possible risk
factors.
Can people do anything to prevent telomere shortening? It
looks like you can, by changing your lifestyle. Observational studies
show that exercise, nutritional supplements and reducing psychological
stress can help. Chronic high stress and smoking can lead to accelerated telomere shortening .
What made you decide to help launch the company Telome Health , which is selling a test for telomere length? There
was a lot of interest from the research community and also from
individuals. We had a cost-effective assay in our lab which we
transferred to a company to provide as a service. We are running a study
called "Know your telomeres ".
The goal is to learn more about telomere length and other markers of
ageing, how best to measure these markers, how they are related to
health and lifestyle, and how people respond to learning their own
telomere length results. People were pounding down the doors to enrol.
Is this another step on the road to commercialised personal genetic testing? Right
now, the company only offers the tests as a part of research studies.
Tests for the public, through their physician, will go on sale later in
the year, costing under $200.
What exactly does the telomere test entail? It
is like a cholesterol test. We can take a measurement from blood
samples, cheek swabs or saliva. Specifically, we measure the telomere
length in white blood cells. Cells from the immune system act a bit like
a report card, an indicator for all kinds of conditions.
Have you made any lifestyle changes based on the results of your research? I've learned a meditation technique. I exercise as often as I can. Walking is good too.
Zdroj: New Scientist
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U.S. tests bin Laden's DNA, used facial ID: official
The United States is conducting DNA testing on slain al Qaeda leader Osama bin Laden and used facial recognition techniques to help identify him, a U.S. official said on Monday.
Bin Laden was identified by the assault force that killed him in a firefight in Pakistan in which he resisted and was shot in the head, the official said on condition of anonymity.
Results of the DNA tests should be available in the next few days, the official told Reuters.
The strike force was on the ground for less than 40 minutes and the operation was watched real-time by CIA Director Leon Panetta and other intelligence officials in a conference room at CIA headquarters in Langley, Virginia, the official said.
"When word came in that the operation was a success, CIA officials in the conference room had a rather large applause," the official said.
Zdroj: Reuters.com
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World on alert after U.S. kills bin Laden
Osama bin Laden was killed in a U.S. assault on his Pakistani compound on Monday, then quickly buried at sea, in a dramatic end to the long manhunt for the al Qaeda leader who had become the most powerful symbol of global terrorism. World leaders hailed bin Laden's death but the euphoria was tempered by fears of retaliation and warnings of the need for renewed vigilance against attacks. The death of bin Laden, who achieved near-mythic status for his ability to elude capture under three U.S. presidents, closes a bitter chapter in the fight against al Qaeda, but it does not eliminate the threat of further attacks. The September 11, 2001, attacks, in which al Qaeda militants used hijacked planes to strike at economic and military symbols of American might, spawned two wars, in Afghanistan and Iraq, inflicted damage on U.S. ties with the Muslim world that have yet to be repaired, and redefined security for air travelers. A small U.S. strike team, dropped by helicopter to bin Laden's compound near the Pakistani capital Islamabad under the cover of night, shot dead the al Qaeda leader in a firefight, U.S. officials said. "This was a kill operation," one security official told Reuters, but added: "If he had waved a white flag of surrender he would have been taken alive." The revelation that bin Laden was living in a three-story residence in the military garrison town of Abbottabad, and not as many had speculated, in the country's lawless western border regions, is a huge embarrassment to Pakistan, whose relations with Washington have frayed under the Obama administration. President Barack Obama, whose popularity suffered from continuing U.S. economic woes, will likely see a short-term bounce in his approval ratings. At the same time, he is likely to face mounting pressure from Americans to speed up the planned withdrawal this July of U.S. forces from Afghanistan. However, Bin Laden's death is unlikely to have any impact on the nearly decade-long war in Afghanistan, where U.S. forces are facing record violence by a resurgent Taliban. Many analysts see bin Laden's death as largely symbolic since he was no longer believed to have been issuing operational orders to the many autonomous al Qaeda affiliates around the world. Financial markets were more optimistic. The dollar and stocks rose, while oil and gold fell, on the view bin Laden's death reduced global security risks. BURIED AT SEA, WARNINGS OF REVENGE Within hours of the deadly raid, Bin Laden's body was buried at a sea to prevent his gravesite from becoming a rallying point for his followers, U.S. officials said. Muslim religious rites were conducted on the deck of a U.S. aircraft carrier in North Arabian Sea, a defense official said. "You wouldn't want to leave him so that his body could become a shrine," one U.S. official said. Mindful of possible suspicion in the Muslim world that U.S. forces may have gotten the wrong man, a U.S. official said DNA testing showed a "virtually 100 percent" match with the al Qaeda leader. His body was also identified by one of his wives, an intelligence official said. Fearful of revenge attacks, the United States swiftly issued security warnings to Americans worldwide. CIA Director Leon Panetta said al Qaeda would "almost certainly" try to avenge bin Laden's death. "Though Bin Laden is dead, al Qaeda is not. The terrorists almost certainly will attempt to avenge him, and we must -- and will -- remain vigilant and resolute," Panetta said. France's President Nicolas Sarkozy hailed the killing as a coup in the fight against terrorism, but he, too, warned it did not spell al Qaeda's demise. British Prime Minister David Cameron said the West would have to be "particularly vigilant" in the weeks ahead. U.N. Secretary-General Ban Ki-moon hailed bin Laden's death as a "watershed moment in our common global fight against terrorism." U.S. officials said bin Laden was found in a million-dollar compound in Abbottabad, 35 miles north of Islamabad. After 40 minutes of fighting, bin Laden, three other men and a woman, who U.S. officials said was used as a human shield, lay dead. A source familiar with the operation said bin Laden was shot in the head after the U.S. military team, which included members of the Navy's elite Seals unit, stormed the compound. Television pictures from inside the house showed bloodstains smeared across a floor next to a large bed. It was the biggest national security victory for the president since he took office in early 2009 and will make it difficult for Republicans to portray Democrats as weak on security as he seeks re-election in 2012. In sharp contrast to the celebrations in America, on the streets of Saudi Arabia, bin Laden's native land, there was a mood of disbelief and sorrow among many. The Palestinian Islamist group Hamas mourned bin Laden as an "Arab holy warrior." But many in the Arab world felt his death was long overdue. For many Arabs, inspired by the popular upheavals in Egypt, Libya and elsewhere over the past few months, the news of bin Laden's death had less significance than it once might have. PAKISTAN TOLD AFTER RAID The operation could complicate relations with Pakistan, a key U.S. ally in the battle against militancy and the war in Afghanistan. Those ties have already been damaged over U.S. drone strikes in the west of the country and the six-week imprisonment of a CIA contractor earlier this year. Pakistani authorities were told the details of the raid only after it had taken place, highlighting the lack of trust between Washington and Islamabad. "For some time there will be a lot of tension between Washington and Islamabad because bin Laden seems to have been living here close to Islamabad," said Imtiaz Gul, a Pakistani security analyst. Bin Laden was finally found after U.S. forces discovered in August 2010 that one of his most trusted couriers lived in an unusual and high-security building in Pakistan that had few outward facing windows and no Internet or telephone access. "After midnight, a large number of commandos encircled the compound. Three helicopters were hovering overhead," said Nasir Khan, a resident of the town. "All of a sudden there was firing toward the helicopters from the ground," said Khan, who watched the dramatic scene unfold from his rooftop. Thousands of cheering and flag-waving people converged on the White House after Obama made his televised announcement. Similar celebrations erupted at New York's Ground Zero, site of the World Trade Center twin towers destroyed on September 11. "I never figured I'd be excited about someone's death. It's been a long time coming," said firefighter Michael Carroll, 27, whose firefighter father died in the September 11 attacks. Former President George W. Bush, whose eight-year presidency was defined by the September 11 attacks after he launched a global "war on terror" to root out Islamic militants, called the operation a "momentous achievement". The United States is conducting DNA testing on bin Laden and used facial recognition techniques to help identify him, the official said.
Zdroj: Reuters.com
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Nutrigenomic data may open up ‘goldmine’ of new information, says expert
Understanding the fine details of physiology, rather than looking at
surrogate biomarkers of health and disease, can open up new doorways and a
‘goldmine’ of information on how the diet affects our health, according to a
leading nutrigenomics expert.
In the third part of our special on Nutrigenomics ,
we speak with Dr Ben van Ommen executive director of NuGO (Nutrigenomics
Organization), and head of nutrigenomics at TNO Quality of Life, who says that
the field of nutrigenomics is focused on the need for biomarkers that capture
health improvements, rather then health deterioration.
“This is a concept that originates from the nutrigenomics community,”
says van Ommen.
“There is major interest from society and from industry in the area. It’s
part of a major societal change, where personal health is becoming an important
issue. The question is; is the science up to it?” he added.
NuGo is an organization which provides a network for researchers and
organizations to, enabling them to disseminate information and work together to
learn more about nutrigenomics.
Passion for health
Speaking with NutraIngredients, van Ommen said that that his passion in life
“is to make the population healthier, through any means.” He added that
this means exploiting systems biology, and understanding physiology “in all
of its detail.”
“If you want to study the influence of diet on health, then you need to be
able to measure very carefully, because the effects are subtle. You just don’t
see major change,” explained van Ommen.
Looking at the genetics and gene expression is part of one part of the search
for more information; van Ommen explains that is important to see all of the
“subtleties in the processes that are taking place in an organ or tissue in
the body.”
However he adds that the real challenge is knowing what to do we do with the
masses of data coming out of nutrition and nutrigenomic studies in the future.
However as this knowledge base grows, van Ommen suggests that we will begin
to build up data sets that will not just be useful for meta-analysis of study
outcomes, “but to bring the data together and do full analysis of the overall
data.”
“Suppose we could analyze gene expression analysis in white blood cells,
for all trials that have used omega-3 fatty acids … We would not just be looking
at the phenotypic outcomes, or at biomarkers, but we could look at every single
detail,” explained van Ommen.
However, he warned that another major challenge in the field of nutrigenomics
is “a conceptual innovation challenge.”
“So far nutrition has used classic biomarkers borrowed from biomedical
areas, LDL-cholesterol, inflammatory markers, for example … But if we want to
maintain health, or even better to optimize health, then these biomedical
markers are essentially worthless,” he argued.
“These values are markers of ill health; if I am not ill then they will be
‘normal’; they do not tell me anything else… So then how do we measure if health
improves, rather than health deteriorates?” added van Ommen.
Challenging the system
Dr van Ommen explained that the concept of using a challenge or stress test
“is essential for quantifying optimal health.”
“The role of nutrition is to make sure that I can cope with challenges,
changes, and stress … So therefore use the concept of a stress test to determine
the role of diet in aspects of optimal physiology,” he said.
“This involves developing a nutrigenomics based stress test; to challenge
for example the immune system, and measure all inflammatory biomarkers … This is
what we need,” said van Ommen.
He said that by measuring over 100 proteins, and more than 200 lipid markers,
nutrigenomics can “really tell us what is going on in detail.”
“This way we capture the subtleties of a response,” he said.
Moving forward
“Our strategy is that in the next two years we will have a solid base,
from proof of principle and human intervention studies … Through this we hope to
demonstrate the optimization of health using nutrigenomic based stress
tests,” explained van Ommen.
He said that after this the second phase will be to demonstrate these
benefits for dietary products and the following interactions with regulator
agencies.
Zdroj: web
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Some genetic tests should be 'prescription only'
Should "pharmacogenetic" tests, designed to determine
how people are likely to respond to commonly used drugs, be available
only through a doctor? This question is emerging as a flashpoint, as the
US Food and Drug Administration (FDA) moves to regulate the direct-to-consumer genetic testing industry.
Last week, a panel that advises the FDA on genetic testing held a two-day meeting to consider the risks and benefits of genetic tests. These included the comprehensive genome scans offered by companies like 23andMe , Navigenics and DeCode Genetics .
The panel was asked for its input after the FDA announced last year that it intends to regulate the industry . That decision was sparked by the aborted attempt by another genome-scanning company, Pathway Genomics , to begin selling its test kits in pharmacies.
A summary of the panel's deliberations ,
released after the meeting, states that members "generally agreed on
the recommendation that several categories or specific genetic tests
should be offered solely on prescription". These included
pre-symptomatic tests for serious conditions, such as cancer, and
pharmacogenetic tests.
Disease risk
Relatively few of the risk assessments
for different diseases provided by genome-scanning companies would fall
into the first category – although 23andMe does test for some variants
of the BRCA1 and BRCA2 genes , which confer a high risk of early onset breast or ovarian cancer.
But providing information to customers on their likely responses to common drugs
– such as whether they may need a higher or lower dose of the
blood-thinning drug Warfarin, or whether they may suffer severe muscle
pain and weakness after taking cholesterol-lowering statins – is a
significant and growing part of the service offered by genome-scanning
firms.
23andMe agrees that its customers
should not change their medications without seeking medical advice, but
rejects the idea that they should only be able to get pharmacogenetic
information with a prescription.
"We think that healthcare
professionals have an important role to play in pharmacogenetic testing,
but we think they do not have a role to play as gatekeepers," says
Ashley Gould, the 23andMe's general counsel.
Zdroj: New Scientist
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New gene identified as a cause of male infertility
An international research collaboration - including the University of Dundee - has identified a gene responsible for one of the causes of male infertility.
The gene discovery relates to a condition known as round headed sperm, or globozoospermia, which affects a small percentage of men suffering from infertility problems.
Until now the main cause of the condition was unknown but new research involving the University of Strasbourg, Farah Hospital Amman in Jordan, and the University of Dundee has established that a genetic defect has a sterilising effect on the men’s sperm.
'What we have established is a clear cause for this form of male infertility,' said Professor Christopher Barratt, of the Reproductive and Developmental Biology Group in the School of Medicine at Dundee.
'It is not a particularly common condition - around one in 12 men suffer from infertility problems and round headed sperm accounts for only a small percentage of that number. But it is important that we find causes and treatments for all forms of male infertility.
'With this condition, now that we have identified the genetic defect and shown that it is the common cause of round headed sperm, we are able to offer successful treatments and there have been positive results in using assisted conception for families.'
The research was sparked by the identification of a family of five brothers in Jordan who all had globozoospermia, four of whom were found to have the genetic defect. Additionally, other men with the disorder from France and North Africa have been show to have the defective gene.
The study is published in the American Journal of Human Genetics.
More information: American Journal of Human Genetics , Volume 88, Issue 3, 11 March 2011, Pages 344-350. doi:10.1016/j.ajhg.2011.01.018
Provided by University of Dundee
Zdroj: PhysOrg.com
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Could gene tests tell if kids can be sports stars?
Was your kid born to be an elite athlete? Marketers of genetic tests claim the answer is in mail-order kits costing less than $200.
Some customers say the test results help them steer their children to appropriate sports. But skeptical doctors and ethicists say the tests are putting profit before science and have a much greater price tag - potentially robbing perfectly capable youngsters of a chance to enjoy activities of their choice.
"In the 'winning is everything' sports culture, societal pressure to use these tests in children may increasingly present a challenge to unsuspecting physicians," according to a commentary in Wednesday's Journal of the American Medical Association.
Scientists have identified several genes that may play a role in determining strength, speed and other aspects of athletic performance. But there are likely hundreds more, plus many other traits and experiences that help determine athletic ability, said Dr. Alison Brooks, a pediatrician and sports medicine specialist at the University of Wisconsin in Madison.
Brooks and University of Michigan physician Dr. Beth Tarini wrote the commentary to raise awareness about the issue.
A handful of companies are selling these tests online. In some cases, the tests screen for genes that are common even among non-athletes. As science advances, Brooks said, "My guess is we're going to see more of this, not less."
Bradley Marston of Bountiful, Utah, bought a test online a year ago for his daughter Elizabeth, then 9.
She's "a very talented soccer player," and Marston wanted to know if she had a variation of a gene called ACTN3, which influences production of a protein involved in certain muscle activity.
One form of the gene has been linked with explosive bursts of strength needed for activities such as sprinting and weight lifting.
The ACTN3 test sold by Atlas Sports Genetics was developed by Genetic Technologies Limited, an Australian firm. Atlas' $169 kit consists of two swabs to scrape cells from the inside of the cheek. Customers return the used swabs to the Boulder, Colo., company and receive an analysis several days later.
Elizabeth Marston's test showed she has a sprinting-related gene form - results her father hopes will help her get into elite sports programs or win a sports scholarship to college.
Marston said he ordered the test partly out of curiosity, but approached it cautiously and talked with Elizabeth to make sure she could handle it.
"She told me, `Well, Daddy, I just have to try harder'" if the results came back negative, Marston said.
Elizabeth has loved soccer since age 4 and said she's happy with the results.
But even at age 10, she knows it will take more than genes to reach her goal of playing in the Olympics.
"I think I would have to train hard," she said.
Nat Carruthers, operations president for Atlas Sports Genetics, says the company has sold several hundred test kits since it began marketing them in 2008.
"Our goal is to help people become the athlete they were born to be," not to exclude kids from certain sports, Carruthers said.
He said critics have misrepresented the test "to sound like we're telling parents what their kid should do and how good their kid will be. That's not at all our claim or desire," he said.
CyGene Laboratories, based in Coral Springs, Fla., sold a similar $100 swab test online for different sports-related genes until last fall, but it has suspended operations.
CyGene also sold kits online advertised as testing for human diseases, but Mark Munzer, the company's former president, said that industry is reeling from a Food and Drug Administration crackdown last year on efforts to sell disease-related gene tests in retail pharmacies.
The FDA scheduled a hearing on Tuesday to receive feedback from an expert panel on how the agency should be regulating direct-to-consumer genetic tests that make medical claims. Marketers of sports gene tests that don't make medical claims aren't FDA regulated.
University of Maryland researcher Stephen Roth, a specialist in exercise physiology and genetics who has studied the ACTN3 gene, said the science of how genes influence athletic ability "is in its infancy" and that marketers' claims are based on "gross assumptions."
Roth said roughly 80 percent of people worldwide have the ACTN3 gene that has been linked with explosive force. The fact that few of them become elite athletes underscores that it takes more than genes to make a sports star.
Also, about 20 percent of people have a gene variation that inhibits production of the protein involved in explosive force. That doesn't mean they can't excel in sports, Roth said, citing a Spanish long jumper who made it to the Olympics despite lacking that protein.
Dr. Lainie Friedman Ross, a medical ethicist and pediatrician at the University of Chicago, said the tests raise ethical questions when used in children because they're too young to understand the possible ramifications and to give adequate consent.
"This is recreational genetics with a real serious potential for harm," Ross said. "People are going to think, `If my kid has this, I'm going to have to push real hard. If my kid doesn't have it, I'm going to give up before I start," she said. Instead, Ross said, parents should "let kids follow their dreams."
"While parents have the authority to make health care decisions about their children, this type of genetic testing is elective at best and should actively involve the children in the decision-making process," Ross said.
More information: JAMA: http://jama.ama-assn.org
Zdroj: web
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Gene responsible for severe osteoporosis disorder discovered
Scientists have identified a single mutated gene that causes Hajdu-Cheney syndrome, a disorder of the bones causing progressive bone loss and osteoporosis (fragile bones). The study, published in Nature Genetics today, gives vital insight into possible causes of osteoporosis and highlights the gene as a potential target for treating the condition
There are only 50 reported cases of Hajdu-Cheney syndrome (HCS), of which severe osteoporosis is a main feature. Osteoporosis is a condition leading to reduction in bone strength and susceptibility to fractures. It is the most common bone disease, with one in two women and one in five men over 50 in the UK fracturing a bone because of the condition. This represents a major public health problem yet, until this study, possible genetic causes of osteoporosis were poorly understood.
The team of scientists, led by the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre (BRC) at King's College London and Guy's and St Thomas', set out to investigate the genetic cause of HCS in order to detect clues to the role genes might play in triggering osteoporosis.
Using a cutting edge technique for identifying disease-causing genes, known as exome sequencing, the team were able to identify NOTCH2 as the causative gene using DNA from just three unrelated HCS patients. The team then confirmed their findings in an additional 12 affected families, 11 of whom had an alteration in the identical portion of the same gene.
Professor Richard Trembath, Head of King's College London's Division of Genetics and Molecular Medicine and Medicine Director of the NIHR BRC, said: "Up until now, we knew very little about the genetic mechanisms of severe bone disease. But these findings add to our understanding of the uncommon condition of HCS and provide an important basis to develop future studies in more common forms of osteoporosis, including the development of potential new therapies."
Provided by King's College London web
Zdroj: PhysOrg.com
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Scientists discover genetic switch that increases muscle blood supply
Many people suffer from a devastating condition known as critical limb ischemia (CLI) that can lead to muscle wasting and even amputation. The disease is linked to the blockage of blood flow to the skeletal muscle and current treatment options include rehabilitative exercise and surgical bypass of blood vessels. New preclinical research suggests there may be a way to restore blood supply in skeletal muscle without traditional intervention.
Scientists at The University of Texas Health Science Center at Houston (UTHealth) and the Salk Institute for Biological Studies announced in the March 2 print issue of the journal Cell Metabolism that they have identified a genetic switch that can increase the number of blood vessels in the skeletal muscle of non-exercising mice.
Skeletal muscle is composed of two types of fibers: slow twitch fibers that inherently have a dense supply of blood vessels and fast twitch fibers that have fewer blood vessels. The researchers used a gene switch known as estrogen-related receptor gamma (ERR gamma) that when activated in fast twitch fibers of mice by genetic engineering, converts these fibers into slow twitch fibers.
"This consequently resulted in a striking increase in muscle blood supply as measured by imaging and angiography," said Vihang Narkar, Ph.D., lead investigator and assistant professor of molecular medicine at the UTHealth Medical School. "These genetically-transformed muscles also acquire other characteristics of slow muscles, such as improved metabolic capacity and fatigue resistance that can be additionally beneficial in resolving muscle vascular disease."
Narkar, whose UTHealth laboratory is in the Center for Diabetes and Obesity Research at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, said, "The identification of the estrogen-related receptor gamma vascular switch will open potential therapeutic avenues for treating CLI and other cardiovascular diseases linked to defective blood supply."
Colin Barker, M.D., assistant professor of cardiology at the UTHealth Medical School, said new research is needed to help people with peripheral artery disease, particularly those with the most severe form - critical limb ischemia. "Poor circulation in the legs can lead to muscle wasting, infections, severe pain and amputation," he said. "Dr. Narkar's work potentially has many useful applications. It is very much in the translational medicine arena."
"Understanding the gene network that specifies high vascular supply to muscle gives us a new and very powerful tool to promote improved muscle performance and the promise of fitness, especially for those who cannot work out," says Ronald M. Evans, Ph.D., senior author, Howard Hughes Medical Institute Investigator and professor in the Salk's Institute's Gene Expression Laboratory. "This is good news for people with heart disease, frailty, peripheral vascular disease and more generally those who have a variety of medical problems where exercise could be helpful but is not possible to achieve."
In 2010, an estimated 2.8 to 3.5 million U.S. citizens suffered from critical limb ischemia, according to a report by THE SAGE GROUP, an independent research and consulting company specializing in peripheral artery disease. CLI risk factors include diabetes, obesity and smoking.
"Exercise is an important part of any intervention strategy to prevent or treat diabetes mellitus and obesity," said Perry Bickel, M.D., associate professor of medicine at the UTHealth Medical School and director of the UTHealth Center for Diabetes and Obesity Research. "Results by Drs. Narkar and Evans support the notion that in the future we may be able to design drugs that produce the benefits of exercise in order to counteract the damage that diabetes and obesity cause to the body, such as blockages of blood vessels."
Narkar and Evans collaborated on a highly-publicized study published in the journal Cell in 2008 in which they used two investigational exercise mimetic drugs – GW1516 and AICAR – to increase the endurance of non-exercising mice. These drugs target different genetic switches, namely PPAR delta and AMPK.
More information: "Exercise and PGC1-alpha-Independent Synchronization of Type I Muscle Metabolism and Vasculature by ERR gamma," Cell Metabolism.
Provided by University of Texas Health Science Center at Houston ( web )
Zdroj: PhysOrg.com
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Genetic cause uncovered for extreme form of dwarfism
Two Sussex scientists have identified a gene that causes an extreme form of dwarfism, known as primordial dwarfism.
The findings, published on Sunday (27 February) in Nature Genetics, shed light on how human body size is determined, and for the first time make a direct link between the copying of DNA in cells and body growth.
Dr Mark O'Driscoll and Professor Penny Jeggo at the Sussex Genome Damage and Stability Centre, together with a colleague at the MRC Human Genetics Unit in Edinburgh, reveal that the gene ORC1 plays a key role in triggering the copying of DNA.
This discovery could open up new avenues of research into how growth disorders occur and offer people with severe growth disorders a chance of better and earlier diagnosis.
Primordial dwarfism is a group of incredibly rare growth disorders that significantly limits growth at every stage of life, from before birth to adulthood, and includes the smallest people in the world (with an adult height of as little as one metre).
Many of those with primordial dwarfism have small ears and no knee caps. They may also have a reduced head size, in proportion to their body size, in contrast with other forms of dwarfism.
Without a clear understanding of what causes the disorders, it can often be difficult for patients to get an accurate diagnosis and to provide the best management of their condition.
Professor Jeggo says: "It's exciting that a protein complex that plays a key role in how cells copy their DNA has such a significant impact on development.
"This demonstrates that the investment in understanding basic mechanisms underlying cell growth and replication is critical for understanding development of organisms and disorders of human health."
The findings are supported by a second study, by a team at the MRC Human Genetics Unit in conjunction with Radboud University Nijmegen Medical Centre in the Netherlands.
The second study reveals that four further genes also cause primordial dwarfism, suggesting that these genes are important for human growth.
Provided by University of Sussex
Zdroj: web
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Human DNA contaminates a fifth of sequenced genomes
TIME to run a tighter ship? Up to 18 per cent of the
genomes sequenced so far seem to be contaminated with human DNA , likely
because of lax lab practices.
Rachel O'Neill
and colleagues at the University of Connecticut in Storrs went through
2749 genomes, including bacteria, viruses, plants and animals. They
found that 492 were similar in one respect: they contained a snippet of
human DNA called AluY.
Only the influenza genomes were completely clean, probably because there are stringent protocols in place for handling infectious diseases (PLoS One , DOI: 10.1371/journal.pone.0016410 ).
O'Neill did not look at the human
genome, but she says it may also have been contaminated with DNA from
lab workers. She thinks lab practices will have to become tighter,
particularly for projects designed to scan people's genomes for sequences that affect disease . "You wouldn't want to be told that you had a sequence that gives a high risk of cancer when in fact you didn't," O'Neill says.
Zdroj: New Scientist
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Cold cases gone hot: Researchers solve decades-old medical mysteries using genetics
The mystery began in 1976. Adolfo Pampena was diagnosed with a rare form of cancer that caused a strange combination of symptoms and was associated with the occurrence of multiple tumours in his stomach and colon. His medical team was stumped and was unable to answer the most important questions for him and his family: the cause of his disease and the risk for future generations.
Now, 35 years later, the answers are at hand thanks to a genetic study led by investigators at the Research Institute of the McGill University Health Centre (RI MUHC), the McGill Program in Cancer Genetics at the Gerald Bronfman Centre for Clinical Research in Oncology and the Lady Davis Institute for Medical Research at the Jewish General Hospital. The study was recently published in The New England Journal of Medicine.
The researchers were able to pinpoint the gene responsible for the disease (BUB1B), which is involved in the regulation of chromosomal separation. Instability during cell division can result in chromosomes ending up in the wrong place, which can lead to the development of tumours. "The general significance of this discovery is that individuals can be seen at our genetic clinic with an unknown condition and end up with a diagnosis that is relevant to patients and their families," said Dr. William Foulkes, senior author of the study and a researcher in genetics at the RI MUHC, the Lady Davis Institute.
"My father and family were relieved that the cancer risk for other family members is much less than we thought," said Mary Pampena, Adolfo's daughter. "Now we know more about my father's genetic history and the cancers he had. We know what screening test to do in the future. This is important information for us, our children and future generations."
In another study published in the January, 2011 Journal of the American Medical Association (JAMA). Dr. Foulkes details a second solved mystery involving five families with a long history of nontoxic multinodular goiter (MNG). Goiter is a thyroid disease which can lead to extreme swelling of the neck or larynx. The most common form of the disease is not genetic and is due to iodine insufficiency. However, this form of MNG was known to be genetic, but to date, no one had ever localized the specific gene or mutation responsible. Dr. Foulkes, Dr. Marc Tischkowitz (from the Program in Cancer Genetics and the Lady Davis Institute) and their team finally succeeded, and found the mutation in a surprising place.
As it turns out, the mutation, in a gene called DICER1, was extremely unusual, Foulkes said, who is also James McGill Professor of Medicine, Human Genetics and Oncology and Director of the Program in Cancer Genetics at McGill University. "It changes the protein in only one place, and that single change is enough to trigger multinodular goiter. Generally speaking, when you have a mutation in a disease gene, it causes a multitude of problems, not just one illness. But in this case, we have no evidence that it causes anything except goiter.
Intriguingly, women in three of the families had been diagnosed with an unusual type of ovarian tumor called Sertoli-Leydig Cell Tumor and thus Foulkes and his colleagues were able confirm that there is a genetic link between multi-nodular goiter and these rare tumors. This link had first been postulated in 1974.
"In the future, our challenge as researchers is to be able to help people with an unknown condition by finding out rather quickly what the genetic cause of their problem is" explained Foulkes. "We can hope in the long-term to have an impact on treatment, diagnosis and other aspect of management."
Provided by McGill University Health Centre
Zdroj: PhysOrg.com
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Celiac disease and Crohn's disease share part of their genetic background
An investigation has found that celiac disease and Crohn's disease, both inflammatory diseases of the gastrointestinal tract, share at least four genetic risk loci. Together, researchers from the University of Groningen, The Netherlands; the Broad Institute, USA; the Université de Montréal and Montreal Heart Institute in Canada performed a combined meta-analysis of genome-wide data for celiac disease and Crohn's disease. This meta-analysis, published in the open-access journal PLoS Genetics on January 27, has identified two new shared risk loci and two shared risk loci that had previously been independently identified for each disease.
The pathogenesis of both celiac disease and Crohn's disease is only partly understood, although it is known that they are affected by both genetic and environmental risk factors. At least one in every hundred individuals in the Western world develop celiac disease; Crohn's disease is much less common but can be accompanied by more severe symptoms as it can affect the whole gastrointestinal tract. Celiac patients develop an inflammation of the small bowel in reaction to gluten, whereas there is no specific known autoantigen for Crohn's disease. However, the primary cause of Crohn's disease is thought to be a dysregulated immune response to gut bacteria. In order to gain a better understanding of the pathogenesis and to aid in developing therapies against these disorders, knowledge of the genetic background of the diseases is vital.
As it has previously been shown that celiac patients are at a higher risk of developing Crohn's disease than non-sufferers, it had been thought that the two illnesses would share genetic risk loci. This study combined the results from the genetic investigations into both diseases to show that part of the genetic background of Crohn's disease and celiac disease is shared, which confirms a common pathogenesis for these disorders. Although additional studies will be necessary to understand the mechanisms by which these variants influence both Crohn's disease and celiac, the current study provides a proof of principle that risk factors shared across related diseases can be identified by directly combining genetic data from clinically distinct diseases.
Zdroj: PhysOrg.com
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Gene discovery shows parents divided over brain and brawn
Scientists at the University of Bath have discovered a gene that defies conventional rules, with the copies inherited from mum and dad doing two very different jobs.
All animals have two copies of each gene: one inherited from each parent. For most genes, both copies are active, but for some genes, one copy is switched off – a process called imprinting.
The researchers at Bath, working with scientists at the Neuroscience & Mental Health Research Institute in Cardiff University, have found that a gene called Grb10 has both copies active but the copy from the father is only active in the brain, whilst the maternal copy is active in all other parts of the body. It seems that each parent has unwittingly prioritised a different part of the body through the power of genetics – a key question is what is the consequence of this?
The study, published in the prestigious journal Nature, has shown that the two copies actually drive very different processes: the maternal copy is involved in foetal growth, metabolism and fat storage, whereas the paternal one regulates social behaviour in adults.
To confirm this, the researchers studied the behaviour of mice that lacked a copy of Grb10 from their father i.e. the gene was not active in the brain and worked normally in the rest of the body. They found that these mice were more domineering, over-grooming their companions and being more assertive than those with the active gene.
The work, funded from several sources, including the Biotechnology and Biological Sciences Research Council (BBSRC), Medical Research Council and a Wellcome Trust “Value in People” award, gives scientists a better understanding of how imprinted genes work, shedding light on processes that are important for our health and well-being.
Dr Andrew Ward, from the University of Bath’s Centre for Regenerative Medicine, said: “For the first time, we’ve shown that the same gene can have two very different functions depending on which parent each copy is inherited from. It seems that the mother and father are using different strategies to help their offspring, one focussed on the body and the other on the mind.
“Imprinted genes are proving to be important for many aspects of human health. Here is a single gene that may link growth in the womb with both physical and mental health in later life.
“It’s amazing that one gene can affect both brain and brawn in this way. In future research we’d like to investigate how this single gene might have evolved to serve such distinct purposes.”
Dr Alastair Garfield, who carried out the work at Bath and Cardiff but is now working at the University of Cambridge, said: “Grb10 is the first example of an imprinted gene that regulates social behaviour in adults.
“Asserting your dominance over others in your social group can be risky behaviour, and this gene appears to keep that behaviour in check.
“Our study has been in mice, but many genes that are imprinted in mice are also similarly imprinted in humans, so we predict Grb10 could work in a similar way in people.”
Provided by University of Bath
Zdroj: PhysOrg.com
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Blocking "rogue gene" may stop cancer spread: study
British scientists have discovered a "rogue gene" which helps cancer spread around the body and say blocking it with the right kind of drugs could stop many types of the disease in their tracks.
Researchers from the University of East Anglia said their findings could lead within a decade to the development of new medicines to halt a critical late stage of the disease known as metastasis, when cancer cells spread to other parts of the body.
The culprit gene, called WWP2, is an enzymic bonding agent found inside cancer cells, the researchers explained in their study, published in the journal Oncogene Monday.
It attacks and breaks down a naturally-occurring protein in the body which normally prevents cancer cells from spreading.
In tests in the laboratory, the UEA team found that by blocking WWP2, levels of the natural inhibitor protein were boosted and the cancer cells remained dormant.
Surinder Soond, who worked on the study, said it was a "novel and exciting approach to treating cancer and the spread of tumors which holds great potential."
"The challenge now is to identify a potent drug that will get inside cancer cells and destroy the activity of the rogue gene," said Andrew Chantry of UEA's school of biological sciences, who led the research.
He said this was "a difficult but not impossible task" and one that would be made easier by the better understanding of the biological processes gained in this early research.
Chantry said in a telephone interview the findings mean drugs could be developed in the next 10 years that could be used to halt the aggressive spread of many forms of cancer, including breast cancer, brain, colon and skin cancer.
If a drug was developed that deactivated WWP2, he said, conventional therapies such as chemotherapy and radiotherapy could be used on primary tumors with no risk of the disease taking hold elsewhere.
He said his team is now working with other scientists to try to design a drug which could interrupt the gene's activity.
Zdroj: Reuters.com
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The genius of bacteria
Tel Aviv University develops an IQ test to assess and outsmart bacteria's 'social intelligence'
IQ scores are used to assess the intelligence of human beings. Now Tel Aviv University has developed a "Social-IQ score" for bacteria ― and it may lead to new antibiotics and powerful bacteria-based "green" pesticides for the agricultural industry.
An international team led by Prof. Eshel Ben-Jacob of Tel Aviv University's Department of Physics and Astronomy and his research student Alexandra Sirota-Madi says that their results deepen science's knowledge of the social capabilities of bacteria, one of the most prolific and important organisms on earth. "Bacteria are our worst enemies but they can also be our best friends. To better exploit their capabilities and to outsmart pathogenic bacteria, we must realize their social intelligence," says Prof. Ben-Jacob.
The international team was first to sequence the genome of pattern-forming bacteria, the Paenibacillus vortex (Vortex) discovered two decades ago by Prof. Ben-Jacob and his collaborators. While sequencing the genome, the team developed the first "Bacteria Social-IQ Score" and found that Vortex and two other Paenibacillus strains have the world's highest Social-IQ scores among all 500 sequenced bacteria. The research was recently published in the journal BMC Genomics .
Highly evolved communities
The impact of the team's research is three-fold. First, it shows just how "smart" bacteria can really be –– a new paradigm that has just begun to be recognised by the science community today. Second, it demonstrates bacteria's high level of social intelligence –– how bacteria work together to communicate and grow. And finally, the work points out some potentially significant applications in medicine and agriculture.
The researchers looked at genes which allow the bacteria to communicate and process information about their environment, making decisions and synthesizing agents for defensive and offensive purposes. This research shows that bacteria are not simple solitary organisms, or "low level" entities, as earlier believed ― they are highly social and evolved creatures. They consistently foil the medical community as they constantly develop strategies against the latest antibiotics. In the West, bacteria are one of the top three killers in hospitals today.
The recent study shows that everyday pathogenic bacteria are not so smart: their S-IQ score is just at the average level. But the social intelligence of the Vortex bacteria is at the "genius range": if compared to human IQ scores it is about 60 points higher than the average IQ at 100. Armed with this kind of information on the social intelligence of bacteria, researchers will be better able to outsmart them, says Prof. Ben-Jacob.
This information can also be directly applied in "green" agriculture or biological control, where bacteria's advanced offense strategies and toxic agents can be used to fight harmful bacteria, fungi and even higher organisms.
Tiny biotechnology factories
Bacteria are often found in soil, and live in symbiotic harmony with a plant's roots. They help the roots access nutrients, and in exchange the bacteria eat sugar from the roots.
For that reason, bacteria are now applied in agriculture to increase the productivity of plants and make them stronger against pests and disease. They can be used instead of fertilizer, and also against insects and fungi themselves. Knowing the Social-IQ score could help developers determine which bacteria are the most efficient.
"Thanks to the special capabilities of our bacteria strain, it can be used by researchers globally to further investigate the social intelligence of bacteria," says co-author Sirota-Madi. "When we can determine how smart they really are, we can use them as biotechnology factories and apply them optimally in agriculture."
The international research team includes researchers from Israel, Holland, Russia and India.
American Friends of Tel Aviv University ( www.aftau.org ) supports Israel's leading, most comprehensive and most sought-after center of higher learning. Independently ranked 94th among the world's top universities for the impact of its research, TAU's innovations and discoveries are cited more often by the global scientific community than all but 10 other universities.
Internationally recognized for the scope and groundbreaking nature of its research and scholarship, Tel Aviv University consistently produces work with profound implications for the future.
Zdroj: web
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Blocking rogue gene could stop the spread of most cancers
Scientists at the University of East Anglia (UEA) have discovered a rogue gene which – if blocked by the right drugs – could stop cancer in its tracks.
Published today by the journal Oncogene , the discovery is a breakthrough in our understanding of how cancer spreads. It is hoped the research will lead to new drugs that halt the critical late stage of the disease when cancer cells spread to other parts of the body.
The culprit gene – known as WWP2 - is an enzymic bonding agent found inside cancer cells. It attacks and breaks down a natural inhibitor in the body which normally prevents cancer cells spreading. The UEA team found that by blocking WWP2, levels of the natural inhibitor are boosted and the cancer cells remain dormant. If a drug was developed that deactivated WWP2, conventional therapies and surgery could be used on primary tumours, with no risk of the disease taking hold eleswhere.
Lead author Andrew Chantry, of UEA's School of Biological Sciences, said the discovery could lead to the development of a new generation of drugs within the next decade that could be used to stop the aggressive spread of most forms of the disease, including breast, brain, colon and skin cancer.
"The late-stages of cancer involve a process known as metastasis - a critical phase in the progression of the disease that cannot currently be treated or prevented," said Dr Chantry.
"The challenge now is to identify a potent drug that will get inside cancer cells and destroy the activity of the rogue gene. This is a difficult but not impossible task, made easier by the deeper understanding of the biological processes revealed in this study."
The research was funded by UK-based charity the Association of International Cancer Research (AICR), with additional support from the Big C Charity and the British Skin Foundation.
Dr Mark Matfield, scientific co-ordinator of AICR, said: "This is a very exciting new discovery and a perfect example of the way that basic research into cancer can open up ways to develop new ways to treat cancer."
The initial discovery was made while researchers were studying a group of natural cancer cell inhibitors called 'Smads'.
Dr Surinder Soond, who spearheaded the experimental work in the laboratory, said: "This is a very novel and exciting approach to treating cancer and the spread of tumours which holds great potential."
More information: 'Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFβ signalling and EMT' by S Soond (University of East Anglia) and A Chantry (University of East Anglia) is published by Oncogene on January 24 2011.
Zdroj: web
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Genetic sequencing alone doesn't offer a true picture of human disease
Despite what you might have heard, genetic sequencing alone is not enough to understand human disease. Researchers at Duke University Medical Center have shown that functional tests are absolutely necessary to understand the biological relevance of the results of sequencing studies as they relate to disease, using a suite of diseases known as the ciliopathies which can cause patients to have many different traits.
"Right now the paradigm is to sequence a number of patients and see what may be there in terms of variants," said Nicholas Katsanis, Ph.D. "The key finding of this study says that this approach is important, but not sufficient. If you really want to be able to penetrate, you must have a robust way to test the functional relevance of mutations you find in patients. For a person at risk of type 2 diabetes, schizophrenia or atherosclerosis, getting their genome sequenced is not enough – you have to functionally interpret the data to get a sense of what might happen to the particular patient."
"This is the message to people doing medical genomics," said lead author Erica Davis, Ph.D., Assistant Professor in the Duke Department of Pediatrics, who works in the Duke Center for Human Disease Modeling. "We have to know the extent to which gene variants in question are detrimental – how do they affect individual cells or organs and what is the result on human development or disease? Every patient has his or her own set of genetic variants, and most of these will not be found at sufficient frequency in the general population so that anyone could make a clear medical statement about their case."
Davis, working in the lab of Katsanis, and in collaboration with many ciliopathy labs worldwide, sequenced a gene, TTC21B, known to be a critical component of the primary cilium, an antenna-like projection critical to cell function.
While a few of the mutations could readily be shown to cause two main human disorders, a kidney disease and an asphyxiating thoracic condition, the significance of the majority of DNA variants could not be determined. Davis then tested these variants in a zebrafish model, in which many genes are similar to humans, and showed that TTC21B appears to contribute disease-related mutations to about 5 percent of human ciliopathy cases.
The study, which appears in Nature Genetics online on Jan. 23, shows how genetic variations both can cause ciliopathies and also interact with other disease-causing genes to yield very different sets of patient problems.
Katsanis, the Jean and George Brumley Jr., M.D., Professor of Pediatrics and Cell Biology, and Director of the Duke Center for Human Disease Modeling, is a world expert in ciliopathies such as Bardet-Biedl Syndrome, in which the primary cilium of cells is abnormal and leads to a host of problems. About one child in 1,000 live births will have a ciliopathy, an incidence that is in the range of Down's syndrome, said Katsanis.
"By sequencing genes to identify genetic variation, followed by functional studies with a good experimental model, we can get a much better idea of the architecture of complex, inherited disorders," Katsanis said. "Each individual with a disease is unique," Davis said. "If you can overlay gene sequencing with functional information, then you will be able to increase the fidelity of your findings and it will become more meaningful for patients and families."
It will take more laboratories doing more pointed studies like this one to get a fuller picture of the ciliopathies and other diseases, Davis said.
Katsanis noted that it will take true collaboration within many scientific disciplines as well as scientific finesse to get at the true roots of complex diseases.
"Brute force alone – sequencing – will not help," he said. "Technology is of finite resolution. You must have synthesis of physiology, cell biology, biochemistry and other fields to get true penetration into medically relevant information."
Provided by Duke University
Zdroj: PhysOrg.com
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Genes map study finds clues to pancreatic cancer
Experts in the genetics of cancer said on Thursday they have found out why some people can live for years with the same kind of rare pancreatic cancer that affects Apple CEO Steve Jobs.
They identified new genes that, when mutated in a certain way, appear to cause a relatively less harmful form of pancreatic neuroendocrine tumor.
Patients with these mutations lived twice as long as those whose tumors carried other mutations, the team at Johns Hopkins University in Baltimore report in the journal Science.
"This is the new molecular view of cancer. The genetic makeup of the cancer will determine what the management (for) this person would be," Nickolas Papadopoulos, one of the researchers who led the study, said in a telephone interview.
Pancreatic cancer is one of the deadliest cancers, killing 95 percent of patients within five years.
But doctors realize that identifying cancer by the organ where it starts in only a very crude tool. Tumors vary in their aggressiveness and makeup, and studies show that particular genetic mutations may be more useful for deciding how to treat a patient and predicting how well he or she will do.
Pancreatic cancer is diagnosed in nearly 37,000 people a year in the United States and kills more than 34,000, according to the American Cancer Society.
But most of these cases are a type of tumor called adenocarcinoma. Neuroendocrine tumors, which account for about 5 percent of pancreatic cancer cases, are more easily treated and less aggressive. About 40 percent of patients are still alive 10 years later.
BAFFLING CASE
Jobs has baffled experts and shareholders. He said in 2004 he had undergone successful surgery for a pancreatic islet cell neuroendocrine tumor but gave no details.
He had a liver transplant in 2009, which could be a treatment for tumor spread, and just announced on Monday he would go on medical leave again but did not say why.
Papadopoulos and colleagues on Hopkins cancer expert Dr. Bert Vogelstein's team sequenced all the DNA taken from tumors of 68 patients with pancreatic neuroendocrine tumors.
Patients whose tumors had mutations in three genes called MEN-1, DAXX and ATRX had lived at least 10 years after diagnosis, they reported in Science.
More than 60 percent of patients whose tumors did not have these mutations died within five years, they found.
MEN-1 was common, seen in more than 44 percent of the 68 patients.
Zdroj: Reuters.com
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Scientists complete first citrus gene sequencing
Scientists have completed the genetic sequencing of two varieties of citrus trees, a key step in fighting diseases that threaten the global citrus fruit industry, researchers said on Tuesday.
They assembled the genome sequences for sweet orange and Clementine mandarin trees, the first sequencing of any citrus plants, according to University of Florida researchers who led the international team that completed the work.
The Clementine mandarin sequence is the higher quality of the two, but both are expected to help scientists find new ways to fight diseases such as citrus greening, as well as help those working to improve fruit flavor and quality, the researchers said.
Greening is a bacterial disease spread by an insect, the citrus psyllid. It makes the fruit unpalatable and kills the tree within a few years. It has wiped out some citrus crops in Asia, Africa, the Arabian Peninsula and Brazil, and has spread rapidly in Florida since its discovery there in 2005.
Sequencing the plants' genomes involves determining the exact order of the millions of chemical building blocks that make up the genes. Scientists hope to use the data to produce genetically modified trees that resist disease, produce tastier and more nutritious fruit and better tolerate salt, bad soil or extreme temperatures.
Geneticists sequenced the DNA of the greening bacterium in 2009 and expect to soon do the same for the citrus psyllid, data that could help control the pests.
The citrus genome sequences were announced on Saturday at the International Plant and Animal Genome Conference in San Diego.
Officials associated with Florida's $9 billion citrus industry officials said they were thrilled.
"The publication of the sweet orange and tangerine genomes will accelerate the discovery of innovative solutions to a myriad of pest and disease problems that threaten citrus production," said Dan Gunter, chief operating officer of the Citrus Research and Development Foundation Inc.
Michael Sparks, chief executive of the Florida Citrus Mutual growers group, called the research an exciting breakthrough for "the future of not only Florida citrus, but the entire global citrus industry."
The team that worked to obtain the gene sequence for the Clementine mandarin included scientists from the University of Florida, Italy, Brazil, France and Spain and the U.S. Department of Energy's Joint Genome Institute (JGI).
The sweet orange sequencing was done by scientists from the University of Florida, JGI, the Georgia Institute of Technology and 454 Life Sciences, a Roche company.
The sweet orange is grown in more than 100 nations and is one of the most widely grown fruit crops in the world.
Zdroj: Reuters.com
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New technology provides first view of DNA damage within entire human genome
New technology providing the first view of DNA damage throughout the entire human genome developed by Cardiff University scientists could offer a valuable new insight into the development and treatment of conditions like cancer.
Professor Ray Waters, Dr Simon Reed and Dr Yumin Teng from Cardiff University's Department of Genetics, Haematology and Pathology have developed a unique way of measuring DNA damage frequency using tiny microarrays.
Using the new method Cardiff scientists can, for the first time, examine all 28,000 human genes where previous techniques have only allowed scientists to analyse parts of about five human genes.
The new patented technique offers an unprecedented view of DNA damage in humans caused by agents that can create conditions like cancer.
Professor Waters said: "This is really an exciting development and offers us the chance to examine DNA damage in the entire human genome.
"The approach is especially useful to examine the damage to people's DNA that can go on to cause cancer. We can also examine DNA damaging anti-cancer therapeutics and how responses in individual patients vary."
Human DNA can be damaged in many different ways – through radiation, chemicals and events in the body itself. Genetic defects in DNA repair can lead to cancer prone conditions, immunity defects, premature ageing and other problems.
In normal individuals there are many examples of DNA damage being linked to cancer, for example through smoking or over exposure to ultra-violet rays.
There is little evidence as to how DNA repair varies amongst the normal population and how normal individuals cope with anti-cancer therapies that damage the DNA in their cancer cells and normal cells.
The novel technology, developed with funding from the Medical Research Council (MRC) and Cancer Research Wales, will have implications for cancer risk assessment, for cancer diagnostics and for developing new cancer therapeutics.
Professor Ray Waters is Head of Cardiff University's Cancer Studies Interdisciplinary Research Group. Consisting of more than 50 researchers, the Group is working together on new cancer therapeutics and diagnostics which can be taken through to the clinic.
He was deputy chair of the UK Government Committee on Medical Aspects of Radiation in the Environment (COMARE) and he drove its 2009 report on the health risks associated with sunbed usage.
Professor Waters added: "The method has some very exciting potential applications. We are already working alongside companies such as Agilent to see if our method can be used by the chemical and pharmaceutical industries for routine genotoxicity testing. Here, determining whether new agents damage DNA is a crucial step in their development
"The technique could also be used for other purposes like examining DNA damage in the skin from sunburn, and we will be looking to develop this application over the coming months and years.
"For future developments input from our current team of Mark Bennett, Yanbo Deng, Katie Evans, Matthew Leadbitter, Dr James Powell and Dr Shirong Yu will be crucial."
Zdroj: web
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Genetic risk factors identified for coronary artery disease, heart attack
Coronary artery disease (CAD) is the single largest cause of death in adults in the United States. Until recently, the genetic basis of CAD has been largely unknown, with just a few proven genes (typically genes for cholesterol disorders) accounting for very little of the disease in the population. Now, a new study from researchers at the University of Pennsylvania School of Medicine shows that certain genetic profiles increase risk of coronary artery disease (CAD) while others uniquely increase risk of heart attacks in those with CAD.
The findings, published online first today and in an upcoming edition of The Lancet, are the results of the analysis of two genome-wide association studies (GWAS) -- an examination of all or most of the genes (the genome) of different individuals to identify common genetic factors that influence disease.
Lead author Muredach P. Reilly, MBBCH, MSCE, associate professor of Medicine and Pharmacology at Penn, and colleagues compared 12,393 individuals with CAD disorder with 7,383 controls who did not have CAD to identify loci that predispose to angiographic CAD. To identify loci that predispose to heart attacks, they compared 5,783 patients who had angiographic CAD and had a heart attack with 3,644 who had angiographic CAD but no heart attack.
The researchers identified a new locus, ADAMTS7 (a gene already implicated in arthritis), which increased the risk of developing CAD. In the heart-attack comparison, the authors found a new association at the ABO blood group locus. They found that the same gene that codes for the enzyme behind people being blood group O offered protection against heart attacks.
Provided by University of Pennsylvania School of Medicine
Zdroj: PhysOrg.com
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The genetic basis of friendship networks
It's not just our partners that we choose partly because of their genes, we might pick our friends on that basis too. The finding could have implications for studying links between social behaviour and genetics.
People's choice of reproductive partner is known to carry a genetic aspect. To test whether genetics also influences friend choice, James Fowler at the University of California, San Diego, and colleagues studied more than 3000 pairs of friends for which they had genotype information for both individuals. For each friendship pair, the team compared six genes thought to be associated with social behaviour.
They found that friends tended to be more alike than expected by chance for one gene, DRD2, which has been associated with a tendency to alcoholism. The researchers suggest this might be because those carrying the gene find social drinking convivial. In contrast, friends tended to be less alike than expected by chance for another gene, CYP2A6, which may be associated with an open personality. It is not clear why people should prefer friends with different versions of this gene, says Fowler.
The genetic preferences may create previously unrecognised feedback loops. If, for instance, those susceptible to alcoholism choose friends with the same propensity, they may be influenced to drink by social as well as genetic factors. A study that omits this social factor may overstate the effect of DRD2 on their behaviour.
Zdroj: New Scientist
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Researchers aim to resurrect mammoth in five years
Japanese researchers will launch a project this year to resurrect the long-extinct mammoth by using cloning technology to bring the ancient pachyderm back to life in around five years time.
The researchers will try to revive the species by obtaining tissue this summer from the carcass of a mammoth preserved in a Russian research laboratory, the Yomiuri Shimbun reported.
"Preparations to realise this goal have been made," Akira Iritani, leader of the team and a professor emeritus of Kyoto University, told the mass-circulation daily.
Under the plan, the nuclei of mammoth cells will be inserted into an elephant's egg cell from which the nuclei have been removed, to create an embryo containing mammoth genes, the report said.
The embryo will then be inserted into an elephant's uterus in the hope that the animal will eventually give birth to a baby mammoth.
The elephant is the closest modern relative of the mammoth, a huge woolly mammal believed to have died out with the last Ice Age.
Some mammoth remains still retain usable tissue samples, making it possible to recover cells for cloning, unlike dinosaurs, which disappeared around 65 million years ago and whose remains exist only as fossils
Researchers hope to achieve their aim within five to six years, the Yomiuri said.
The team, which has invited a Russian mammoth researcher and two US elephant experts to join the project, has established a technique to extract DNA from frozen cells, previously an obstacle to cloning attempts because of the damage cells sustained in the freezing process.
Another Japanese researcher, Teruhiko Wakayama of the Riken Centre for Developmental Biology, succeeded in 2008 in cloning a mouse from the cells of another that had been kept in temperatures similar to frozen ground for 16 years.
The scientists extracted a cell nucleus from an organ of a dead mouse and planted it into the egg of another mouse which was alive, leading to the birth of the cloned mouse.
Based on Wakayama's techniques, Iritani's team devised a method to extract the nuclei of mammoth eggs without damaging them.
But a successful cloning will also pose challenges for the team, Iritani warned.
"If a cloned embryo can be created, we need to discuss, before transplanting it into the womb, how to breed (the mammoth) and whether to display it to the public," Iritani said.
"After the mammoth is born, we will examine its ecology and genes to study why the species became extinct and other factors."
More than 80 percent of all mammoth finds have been dug up in the permafrost of the vast Sakha Republic in eastern Siberia.
Exactly why a majority of the huge creatures that once strode in large herds across Eurasia and North America died out towards the end of the last Ice Age has generated fiery debate.
Some experts hold that mammoths were hunted to extinction by the species that was to become the planet's dominant predator -- humans.
Others argue that climate change was more to blame, leaving a species adapted for frozen climes ill-equipped to cope with a warming world.
Zdroj: web
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Smoking causes gene damage in minutes
Those first few puffs on a cigarette can within minutes cause genetic damage linked to cancer, US scientists said in a study released.
In fact, researchers said the "effect is so fast that it's equivalent to injecting the substance directly into the bloodstream," in findings described as a "stark warning" to those who smoke.
The study is the first on humans to track how substances in tobacco cause DNA damage, and appears in the peer-reviewed journal Chemical Research in Toxicology, issued by the American Chemical Society.
Using 12 volunteer smokers, scientists tracked pollutants called PAHs, or polycyclic aromatic hydrocarbons, that are carried in tobacco smoke and can also be found in coal-burning plants and in charred barbecue food.
They followed one particular type -- phenanthrene, which is found in cigarette smoke -- through the blood and saw it form a toxic substance that is known to "trash DNA, causing mutations that can cause cancer," the study said.
"The smokers developed maximum levels of the substance in a time frame that surprised even the researchers: just 15-30 minutes after the volunteers finished smoking," the study said.
"These results are significant because PAH diol epoxides react readily with DNA, induce mutations, and are considered to be ultimate carcinogens of multiple PAH in cigarette smoke," the study said.
Lead scientist Stephen Hecht said the study is unique because it examines the effects of inhaling cigarette smoke, without interference from other sources of harm such as pollution or a poor diet. "The results reported here should serve as a stark warning to those who are considering starting to smoke cigarettes," Hecht said.
Lung cancer kills about 3,000 people around the world each day, and 90 per cent of those deaths are attributable to cigarette smoking.
The research was funded by the National Cancer Institute.
Zdroj: web
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Forensic test to identify hair color from DNA
Watch out would-be criminals, because new tools are on the way that could make crime pay even less. A group of European researchers has laid the foundation for a test that can identify hair color from DNA in a tiny drop of saliva, blood or body fluid left at a crime scene.
The researchers say this would be useful when police are hungry for any piece of information and current DNA databases don't turn up any leads.
"Tools that allow us to know what an unknown person looks like can be incredibly useful," said Manfred Kayser, a professor of forensic molecular biology at Erasmus University Medical Center Rotterdam in the Netherlands, who authored the study with colleagues.
One Hair, Two Hair, Red Hair, Blue Hair
The team took hair samples from 385 people living in southern Poland and categorized them into seven different hair shades, ranging from light blond to black. Kayser and his colleagues then sequenced the DNA from the samples, focusing on 11 genes with 13 markers -- sequences of DNA that have a known location and are associated with a specific trait. The study was published this week in the journal Human Genetics.
They were able to determine with 90 percent accuracy if someone had red or black hair, and with 80 percent accuracy if a subject had blond or brown locks. The new approach was even able to distinguish between light and dark blond hair, as well as between shades of red.
Kayser said that the test was better at predicting red or black hair due to a natural darkening with age that turns many blonds into brunettes by adulthood.
"Our study was done on adults, and those blonds would not be placed in the blond category anymore," said Kayser. "Therefore, they would be categorized wrongly in our test."
Age isn't the only way for hair color to change, though, Kayser said the test wouldn't work if someone dyes their hair.
"But it's been known for a long time that wearing gloves avoids leaving physical fingerprints, and that's still one of the main ways that people are caught," Kayser said.
Jack Ballantyne, associate director of research at the National Center for Forensic Science at the University of Central Florida in Orlando, said that up until now, only red hair could be predicted by genetic tests.
"By expanding the range of testable hair types in Caucasians to include black, blond and brown hair I would envision that such testing could be used in the short term in a handful of serious cases worldwide that have no suspect," Ballantyne said.
Other forensic specialists agreed that the test's scope would be limited.
"The main forensic utility of any of these types of studies is in facial reconstruction, where the artist does not really know what color hair to put on the reconstruction," said David Foran, director of the forensic science program at Michigan State University in East Lansing. "As is, the artist has to guess or put a hat on the individual."
There may be more room for better gene-based forensic tests in the future, as genome sequencing becomes cheaper and more widely available, according to Jiali Han, assistant professor of medicine at Harvard Medical School in Boston, who studies the genes involved in skin pigmentation.
Genes Create A Police Sketch?
In September 2010, the same research group laid the foundation for a method to estimate a person's age from DNA. They have also developed a test for predicting eye color. Kayser said that a long-term goal of the research group is to find the genes that determine facial morphology, like a round face or high cheekbones. That way, investigators could have a complete physical picture of a suspect -- skin tone, age, eye color, hair color and facial features.
"We know that genes are involved in a major part in facial features. After all, identical twins are identical in the face," Kayser said. "But how many? And which genes? This is all still unknown and a matter of research."
Above all else, Kayser said that building a future forensic toolkit requires adapting to new information and scientific discoveries. In the future, police bulletins may describe exactly who they're looking for -- from head to toe -- without having any eye witnesses.
Zdroj: web
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Fetal genome mapped from mother's blood for first time
For the first time, a fetus has had its entire genome mapped from a sample of its mother's blood. This technical tour de force could open the door to new methods of prenatal genetic diagnosis.
In 1997, researchers led by Dennis Lo of the Chinese University of Hong Kong showed that "floating" fetal DNA can be detected in maternal blood plasma – it passes across the placenta from fetal cells that have broken down.
Lo's discovery sparked a lot of interest, because it raised the possibility of diagnosing genetic problems in a fetus without the need for invasive procedures such as chorionic villus sampling (CVS) or amniocentesis to extract fetal cells, both of which carry a small risk of inducing a miscarriage.
But it's hard to distinguish fetal sequences from the larger quantity of a woman's own DNA. This has so far largely limited practical applications of the technique to unambiguous situations in which particular fetal genes are not carried by the mother. For instance, fetal sex can be determined by detecting sequences from the male Y chromosome. It's also possible to identify fetuses at risk of rhesus disease , where the mother's immune system attacks a protein on her fetus's red blood cells, by looking for the gene for this rhesus protein in the blood of women who are rhesus negative.
Lo has previously worked on methods to detect fetuses with Down's syndrome from floating fetal DNA. Now, through a combination of brute-force DNA sequencing and sophisticated bioinformatics, his team has shown that it should be possible to detect any genetic disease from a sample of a pregnant woman's blood.
Match and contrast
Lo recruited a couple who were at risk of having a child with beta-thalassaemia , an inherited form of anaemia. By comparing the father's genome and fetal DNA extracted by CVS with billions of fragments of DNA from the woman's blood, Lo was able to construct maps of the entire fetal and maternal genomes. This revealed that the fetus was a carrier of beta-thalassaemia, but was not itself afflicted by the condition.
Of course, the whole point of sampling maternal blood is to avoid performing CVS or amniocentesis. But Lo says that this was just a proof of principle – in practice it should be possible to distinguish fetal and maternal sequences by comparing the fragments obtained from the woman's blood sample with DNA sequenced from her relatives.
Showing that the entire fetal genome is present in a pregnant woman's blood is an important development, says Diana Bianchi , a specialist in prenatal genetic diagnosis at Tufts University in Boston. "This paper is beautiful," she says.
However, at present the analysis is too cumbersome and expensive for clinical use. "At this moment, it would probably cost $200,000 per case," says Lo. "Cutting costs will be very important."
While sampling the entire fetal genome for genetic defects may remain prohibitively expensive for some while, Lo hopes within a year to develop a test focused on about five important genetic conditions, with the sequencing costing around $2000.
Still, Bianchi believes that the bioinformatics involved in reliably distinguishing fetal from maternal DNA sequences from a blood sample may prove impractical for many clinical labs. She also points out that the latest estimates put the risk of miscarriage associated with amniocentesis as low as 0.06 per cent . "At some point, someone's going to need to do an elegant cost-benefit analysis," she says.
Zdroj: New Scientist
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Census promopts spike in demand for DNA paternity test
DNA paternity tests are on the rise, worrying many about a deterioration of faith and sincerity in the family unit.
During the 5th population census conducted between November 1 and 10, there were two to three times as many DNA tests conducted as in previous years.
As DNA laboratory technology becomes more sophisticated and affordable, the technology is becoming more and more popular. Parents can easily identify whether or not the kids they are raising are actually their own children.
In most cases, fathers who are suspicious of infidelity are the ones requesting the test. Basic paternity tests can cost as little as 2,000 yuan.
In Beijing, the Center of Forensic Sciences under Beijing Genomics Institute is one of the most popular centers. The center is licensed by the Ministry of Justice and has persuasive authority.
The number of tests requested at the center has grown 10 to 20 percent each year, said Deng Yajun, director of the center. The center receives applications from around the country, and has conducted more than 2,000 tests each year since 2008.
“Most of the families who come to us are those with more than one kid,” the director said. “In most cases, fathers are the applicants as the mothers are usually clear of the relationship.”
“One father who brought in his 8-year-old son, asked us to determine whether the boy had any genetic relationship with him. The results showed the boy could not possibly be his child,” the director said.
The results have started a lot of family quarrels among parents who emphasize the need for a genetic relationship between family members.
In Shanghai, 20 to 30 percent of paternity tests reveal that the man cannot be the father of the child. In Yangzhou, Jiangsu Province, the figure is 40 percent. In Guangzhou, Guangdong Province, the figure is a staggering 80 percent.
The sudden spike in testing requests during the census caught the attention of media outlets in Beijing, Guangzhou, Shanghai and Chongqing.
Some scholars have called for a limiting of DNA testing availability to ensure familial stability. Many would prefer DNA tests to be the exclusive domain of the justice department.
“The availability of these tests breeds suspicion and doubt in families,” Ma Yinan, a law professor at Beijing University, said. “The situation explodes when the results come back negative.”
But Deng said the commercialization of testing is inevitable. “What we need to change is our way of thinking. Everyone needs to adapt to the fact that this is part of being a developed and progressive society,” she said.
Zdroj: web
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Scientists say rare plant has biggest genome yet
When it comes to genomes, size matters -- and British scientists say a rare and striking plant native to Japan is in a perilous position.
Researchers at Britain's Kew Botanical Gardens say the plant, Paris japonica, has the largest genome yet recorded, putting it at high risk of extinction.
"Some people may wonder what the consequences are of such a large genome and whether it really matters if one organism has more DNA than another," said Ilia Leitch, a researcher at Kew's Jodrell Laboratory. "The answer to this is a resounding 'yes'"
"Having a large genome increases the risk of extinction. The larger it is, the more at risk you are."
The vast range of genome size -- the amount of DNA -- in plants and animals has long fascinated and puzzled scientists.
With 152.23 picograms (pg) of DNA, the Paris japonica has around 15 percent more than the previous record holder, the marbled lungfish or Protopterus aethiopicus, with 132.83 pg.
It is also more than 50 times bigger than the human genome, which is 3.0 picograms. A picogram is one trillionth of a gram.
Leitch said the importance of size lies in the fact that the more DNA there is in a genome, the longer it takes for a cell to copy all of its DNA and divide.
"The knock-on effect of this is that it can take longer for an organism with a larger genome to complete its life cycle than one with a small genome," she said.
This explains why many plants living in deserts which must grow quickly after rains have small genomes enabling them to grow rapidly, while species with large genomes grow much more slowly and are not found in such harsh habitats.
Leitch said that in plants, research has shown that those with large genomes are at greater risk of extinction, are less adapted to living in polluted soils and are less able to tolerate extreme environmental conditions, factors which she said were "all highly relevant in today's changing world."
The smallest genome so far reported is in a parasite of humans and other mammals called Encephalitozoon intestinalis, which has just 0.0023 picograms of DNA.
The record holder among plants for 34 years was a species called Fritillaria assyriaca, until earlier this year when a group of Dutch scientists found that a natural hybrid of trillium and hagae, related to the herb paris, had a genome four percent larger than the fritillary at 132.50 pg.
According to Kew's scientists, this had been widely thought to be around maximum size a genome could reach until the recent discovery of the 152.23 pg Paris japonica genome.
The latest finding was reported in the Botanical Journal of the Linnean Society.
Zdroj: Reuters.com
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Personal genomics tests prompt lifestyle changes
Could a small dose of genetic information cure
complacency about weight loss and exercise? That's the suggestion made
by a new study of how information from "personal genomics" companies has
influenced their customers.
David Kaufman of the Genetics and Public Policy Center in Washington DC quizzed 1048 customers who had ordered genome scans from Decode Genetics of Reykjavik, Iceland, 23andMe of Mountain View, California, or Navigenics , based in Foster City, California.
Asked about changes in their behaviour
between two and six months after receiving the results, 34 per cent of
respondents said they were being more careful about their diet, 14 per
cent said they were doing more exercise, and 16 per cent had changed
their medications or dietary supplements.
"I was surprised at the number of
people who said they'd made changes already," says Kaufman, who revealed
the results this week at the annual meeting of the American Society of Human Genetics (ASHG) in Washington DC.
That's impressive because getting
people to adopt more healthy lifestyles is notoriously difficult – even
when family history shows a high risk of conditions like type 2 diabetes
and heart attacks.
Right thing, wrong reasons?
But responses to genetic information
may be out of proportion to its actual predictive value. For most common
diseases, the genome scans available now explain relatively little
about your future risks. In the case of type 2 diabetes, for example,
diet and exercise play a greater role in risk than genetics does, and
the DNA variants discovered so far explain only a small proportion of the disease's heritability.
Even so, if genetic information has a
disproportionate effect in getting people to heed advice that they
should be following anyway, that could be a strong force for improving
public health.
David Marrero ,
a specialist in diabetes prevention at Indiana University in
Indianapolis, says he is impressed by reported changes in behaviour, but
adds, "The question is how long it is sustained."
Early adopters
Kaufman hopes to run follow-up studies
to address that question. Another important issue is whether genetic
information will be similarly motivating when it moves outside the
self-selecting group who now purchase genome scans and becomes part of
mainstream medical practice.
Toby Jayaratne ,
a specialist in health behaviour at the University of Michigan in Ann
Arbor, worries that some people will adopt a fatalistic attitude if told
that they have a genetic predisposition to a particular disease, and
become less likely to act to improve their health. This is more likely
among poor and socially disadvantaged people, she adds.
Customers of personal genomics firms
are typically relatively wealthy and well-educated. The same is true of
those who have joined academic studies of the effects of providing
genetic information on health behaviour. "They tend to be people who are
highly motivated health-seekers and science geeks," says Barbara Bernhardt of the University of Pennsylvania in Philadelphia, who has conducted detailed interviews with 60 volunteers in the Coriell Personalized Medicine Collaborative , a pioneering effort to study the medical value of genetic information.
Risk judgements
Bernhardt's findings, also revealed at
the ASHG meeting, suggest that people tend to focus mainly on whether
their genetic risks for each condition are higher or lower than average,
rather than paying close attention to the size of those risks. This
means that people might be paying undue attention to risks that are not
actually significantly elevated.
Kaufman, meanwhile, has found that a
minority of his respondents misunderstand the "relative risk" figures
provided by personal genomics firms, particularly when the risks are
below average – a relative risk of 0.8, for instance, indicates that the
person tested is 20 per cent less likely to develop a condition than a
typical member of the same population.
However, despite these glitches, he
finds little evidence that people are misinterpreting genetic
information in ways that might be dangerous to their health. Those who
said they had changed medications, for instance, had overwhelmingly done
so in consultation with their doctor.
"We don't give people enough credit to
people's abilities to decide what's useful to them," Kaufman suggests.
"People who get their data are generally pleased with it, and they
respond in generally positive ways."
Zdroj: New Scientist
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Have gene findings taken the stigma from ADHD?
For the first time, evidence has emerged of genetic
mutations linked to attention-deficit hyperactivity disorder. But how
strong is the link, and how far does the finding undermine claims that
children with the condition are simply naughty kids, victims of bad
parenting or driven to hyperactivity by dietary additives?
What did the researchers do?
A research team in the UK screened DNA
across the entire genome from 366 children with ADHD and 1047 children
without the condition for rare but massive regions of DNA that were
either missing from where they should be or duplicated. They looked for
these abnormalities, called copy-number variants or CNVs, because some
had been linked previously with other psychiatric disorders, including
schizophrenia and autism.
And what was the result?
They found that 16 per cent of the
children with ADHD had abnormally high numbers of CNVs, double the 8 per
cent of normal children who had them: the ADHD children had double the
risk of carrying these genetic abnormalities.
Is that a big deal?
"We have the first scientific evidence of a direct genetic link," said their leader, Anita Thapar of Cardiff University, at a press conference in London.
Another researcher contacted by New Scientist
agreed that the findings were important, groundbreaking and reliable.
"It is a significant finding, and it's by far the largest genetic effect
seen so far," says Philip Asherson , who studies the genetics of ADHD at the Institute of Psychiatry in London.
Did they find anything else to strengthen the conclusions?
Yes. Most strikingly, the rate of CNVs
was six times as high as normal in ADHD children who had IQs lower than
70 and so had a more severe form of the disorder – there were 50 such
children. "That's huge," says Asherson.
Also, the ADHD children had CNVs in
sites on chromosome 16 that overlapped with CNVs previously found in
children with schizophrenia. The implication, says Asherson, is that
these regions may be crucial to development of the brain in the womb or
in infancy, and that disruption in this region may play a role in many
psychiatric conditions.
But the researchers found the CNVs
in only 16 per cent of the ADHD kids. Might bad parenting or poor diet
have caused the disorder in all the rest?
Possibly. But the researchers say that
when diet has been fingered as a culprit in ADHD and changed in an
attempt to treat the condition, little good has come of it. And many
children with ADHD have stable relationships with parents and are well
behaved generally – their condition manifests itself only through an
inability to concentrate and focus on specific tasks. "There's not a
great deal of evidence for what the environmental factors might be,"
said Thapar's colleague Kate Langley.
Might other genes be involved?
Thapar stressed that her findings are
"only the start of unravelling the genetics", pointing out that her team
searched only for the biggest known CNVs, covering 500,000 base-pair
units of DNA or more. Asherson agrees, saying that unpublished research
shows links with smaller CNVs.
Previous studies have found weak links with other genes , particularly those that make components of the brain's "reward" circuitry, such as receptors for the neurotransmitter dopamine .
One of the main hypotheses to explain
ADHD is that the reward system in the brain is defective in some way,
producing such transitory satisfaction that sufferers become bored
quickly and constantly seek out new stimulation to "top up" the reward
circuit.
Another possibility is that ADHD children have an abnormal sense of time , so they perceive short spells as inordinately long and boring.
So where does all this leave diagnosis and treatment?
Thapar stressed that ADHD is treatable both with drugs such as Ritalin
and through behavioural therapy, and that the ultimate cause of the
condition in each case wouldn't affect current treatments, because
knowing genes could be to blame would probably not change which
treatment a doctor recommends. Also, existing methods for diagnosing
ADHD are fine, she says, although screening for certain CNVs could one
day be helpful in some people who have intellectual disability.
Does it mean that ADHD is inheritable?
Too early to say, but when the
researchers looked in more detail at 15 specific CNVs, they found that
11 came from the children's parents, suggesting the possibility of
inheritance. But equally significantly, the remaining four were not
inherited and so must have emerged either in the womb or during
childhood, suggesting that environmental factors may account for them.
Asherson says previous studies have looked for links between ADHD and
smoking during pregnancy, but the findings have been inconclusive.
Finally, does it mean that we're any closer to knowing the exact cause of ADHD and whether the condition is being overdiagnosed in children who are simply going through a naughty phase?
ADHD is so complicated that all sorts
of factors feed into it, but what these findings do prove once and for
all is that there is indeed a genetic component to a condition that we
already know tends to run in families. Now comes the tricky part –
teasing apart the interaction between genes and the environment, and
turning this into new ways to treat the condition.
Zdroj: New Scientist
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Study finds first evidence that ADHD is genetic
British scientists have found the first direct evidence attention deficit/hyperactivity disorder (ADHD) is a genetic disorder and say their research could eventually lead to better treatments for the condition.
Researchers who scanned the gene maps of more than 1,400 children found that those with ADHD were more likely than others to have small chunks of their DNA duplicated or missing.
Anita Thapar, a professor psychiatry at Cardiff University who led the study, said the findings should help dispel the myths that ADHD is caused by bad parenting or high-sugar diets.
"This is really exciting because it gives us the first direct genetic link to ADHD. Now we can say with confidence that ADHD is a genetic disease and that the brains of children with this condition develop differently to those of other children," she told reporters at a briefing about the findings.
ADHD is one of the most common child mental disorders and is estimated to affect around 3 to 5 percent of children globally. It is seen far more often in boys than in girls.
Children with ADHD are excessively restless, impulsive and easily distracted, and often experience difficulties at home and in school. There is no cure, but the symptoms can be kept in check by a combination of medication and behavioural therapy.
Millions of people take ADHD drugs including Novartis's Ritalin, known generically as methylphenidate, Johnson & Johnson's Concerta, Shire's Adderall and Vyvanse and Eli Lilly's Strattera. Global sales of ADHD drugs were around $4 billion dollars in 2009, according to pharmaceutical analysts at Deutsche Bank in London.
NO DIAGNOSTIC TEST IN SIGHT
Thapar said the findings would help unravel ADHD's biological basis, "and that's going to be really important in the future to develop new and much more effective treatments".
But experts stressed that the DNA findings were unlikely to lead the development of a genetic test for ADHD, since a complex mix of genes and environment are likely to be the cause.
"It is not clear that this will yet lead to a diagnostic test, but may well open up new avenues for understanding the neurobiology of the disorder," said Philip Asherson of the Institute of Psychiatry King's College London.
The study also showed an overlap between the deleted or duplicated DNA segments, known as copy number variants (CNVs), and genetic variants linked to the brain disorders autism and schizophrenia -- providing what the scientists said was "strong evidence" that ADHD is a neurodevelopmental condition.
The Cardiff team analysed the genomes of 366 children with ADHD and compared them with 1,047 samples from children without ADHD to try to find variations in their genetic make-up.
The findings, published in The Lancet medical journal, showed that rare CNVs were almost twice as common in children with ADHD compared to the other children.
Nigel Williams, who also worked on the study, noted the significant overlap between CNVs found in children with ADHD and regions of the gene map which are known to influence susceptibility to autism and schizophrenia.
He said the most marked overlap was found at a particular region on chromosome 16 which has been linked to schizophrenia and other major psychiatric disorders and spans a number of genes, including one known to play a role in brain development.
"We have seen a clear genetic link between these segments and other brain disorders," he said. "These findings give us tantalising clues to the changes that can lead to ADHD."
Zdroj: Reuters.com
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Genes offer opportunities for growth, study finds
Upset because you are too short or too tall? An international DNA scan shows it may not be as easy as blaming a parent for passing along the wrong gene.
The researchers identified more than 100 different genes related to height, and said this likely accounted for about 20 percent of all the genes involved.
The finding, published in the journal Nature, shows the trait may be even more complex than anyone thought.
"Height clearly has a lot to do with genetics -- shorter parents tend to have shorter children, and taller parents tend to have taller children," Dr. Joel Hirschhorn of Children's Hospital Boston, who worked on the study, said in a statement.
"This paper is the biggest step forward to date in understanding which of the genetic variants that differ between people account for our differences in height."
Nearly 300 researchers from 100 different institutions pooled their resources for the study, which looked at the genes of 180,000 people.
"These investigators had once been competing with each other to find height genes, but then realized that the next step was to combine their samples and see what else could be found," said Karen Mohlke of the University of North Carolina, who worked on the study.
"The competitors became collaborators to achieve a common scientific goal."
The team looked at the entire genetic map, a scientific fishing expedition called a genome wide association study. While they found some genes in surprising areas, many clustered in expected places such as genetic regions linked with skeletal growth defects.
About 80 genes had been linked to height before.
"We have identified more than 100 novel loci (gene locations) that influence the classic polygenic trait of normal variation in human height, bringing the total to 180," the researchers wrote.
The consortium has nicknamed itself GIANT for Genetic Investigation of Anthropometric Traits.
Zdroj: Reuters.com
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Gene studies zero in on breast, ovarian cancer risk
Scientists have found a region of DNA that can increase or decrease the high chance of breast cancer linked to a particular gene variant - a finding that could help doctors keep a closer eye on women most at risk.
The findings were published in the journal Nature Genetics on Sunday along with two other separate studies linking this same region and four others to ovarian cancer.
The breast cancer study centered on women who carry a faulty BRCA1 gene, which significantly raises the risk of developing certain cancers. On average, around 60 percent of women with a family history of the disease who also carry either a faulty BRCA1 or BRCA2 gene will develop breast cancer. Around 40 percent of these women will develop ovarian cancer, by the age of 70.
The studies found that if a woman with a BRCA1 fault also carries a "risk version" of a DNA region known as 19p13, her breast cancer risk may be even higher still.
"We've found a DNA region that acts like a volume control - to turn up or down the risk of developing breast cancer from faults in the BRCA1 gene," said Antonis Antoniou of Cambridge University, who led the work on the first study.
"Our discovery is the first step in a much larger study to identify genetic factors that modify breast cancer risk in women carrying BRCA1 mutations, and ultimately could help us assess the risk for each woman and monitor for the disease."
Breast cancer is the most common cancer among women, with more than a million new cases diagnosed worldwide each year.
In a separate study, the same 19p13 region was also shown to increase the risk, to a lesser degree, of ovarian cancer in women who are not carriers of a BRCA1 fault.
"This is important because it suggests that women who carry certain versions of this DNA stretch could benefit from closer monitoring for both breast and ovarian cancers," said Simon Gayther at University College London, who led that study.
A third study conducting by scientists from Europe, the United States, Canada and Australia found four other separate genetic regions also associated with ovarian cancer risk in the general population.
Ovarian cancer is the fifth most common cancer among women in developed countries. An estimated 230,000 women worldwide are diagnosed it each year and it kills around 130,000 each year.
Most women are not diagnosed until after the cancer has spread, because its symptoms are hard to detect, and nearly 70 percent of those with advanced disease die within five years.
"These latest findings raise the possibility that in the future, women...who are at the greatest risk of developing ovarian cancer because they carry these newly discovered DNA variants can be identified and given closer surveillance to look for early signs of ovarian cancer when it is most treatable," said Andrew Berchuck, a professor of gynecologic oncology at Duke University Medical Center, who worked on the study.
"It also suggests that preventive approaches could be targeted toward these women."
Zdroj: Reuters.com
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Stool DNA test for colon cancer not yet cost-effective
The inexpensive stool tests commonly used to screen for colon cancer can be more effective, and much less costly, than newer tests that look for certain genetic markers in the stool, according to a study published Monday.
The findings, say researchers, indicate that the price of stool DNA testing needs to fall considerably before it can be considered a cost-effective way to screen for colon cancer -- or win reimbursement from Medicare, the government health insurance program for the elderly and disabled.
In general, experts recommend that adults at average risk of colon cancer start routine screening at the age of 50, through any of several standard tests or a combination of tests.
Right now, Medicare pays for screening via colonoscopy, flexible sigmoidoscopy, barium enema and fecal occult blood testing (FOBT).
FOBT detects hidden blood in the stool, which can be a sign of colon cancer or pre-cancerous growths called polyps. Positive results on the screen prompt a follow-up colonoscopy. FOBT, which involves taking stool specimens at home and mailing them to the doctor's office or medical lab, is simple and cheap, and advances in the tests in recent years have increased their sensitivity.
Stool DNA testing, a newer technology, detects certain genetic markers that may signal cancer; as with FOBT, a suspicious result has to be followed up with a colonoscopy.
Currently, the U.S. Preventive Services Task Force does not include stool DNA testing in its list of recommended tests for routine colon cancer screening, and Medicare does not cover it. Some private insurers do, however.
The new study, published in the Annals of Internal Medicine, was done at the request of Medicare officials to estimate the cost-effectiveness of the DNA tests against that of currently covered tests.
Using data from the medical literature, the researchers estimated that stool DNA testing every three to five years would be about as effective at preventing colon cancer deaths as one commonly used FOBT test (Hemoccult II) performed annually.
The DNA test would be less effective, however, than a more sensitive FOBT called Hemoccult-SENSA, as well as a newer method for detecting blood in the feces called immunochemical fecal occult blood testing (iFOBT).
In the absence of any screening, 57 of every 1,000 65-year-old adults would eventually be diagnosed with colon cancer, estimate the researchers, led by Dr. Iris Lansdorp-Vogelaar of Erasmus Medical Center in Rotterdam, the Netherlands.
Colonoscopy screening every 10 years would be the most effective way to trim that number, according to the researchers. Colonoscopy, which allows a visual inspection of the entire colon, can help prevent colon cancer by allowing doctors to spot and remove polyps.
If there were 100-percent compliance with colonoscopy screening, Lansdorp-Vogelaar and her colleagues estimate, 27 out of every 1,000 65-year-olds would be diagnosed with colon cancer in their lifetime. Moreover, they estimate that 10 per 1,000 would die of the disease -- versus 27 with no screening at all.
With stool DNA testing every three years, 37 of every 1,000 65-year-olds would eventually develop colon cancer, and 13 would die. With Hemoccult-SENSA, the more sensitive FOBT analyzed in the study, those figures would be 32 and 10, respectively, according to the researchers.
The iFOBT approach appeared similar in effectiveness to Hemoccult-SENSA.
Zdroj: Reuters.com
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Gene predicts how fast Alzheimer's progresses
People with a specific genetic variation develop Alzheimer's disease at a faster rate than others, U.S. researchers said on Thursday in a finding that may help in the search for drugs to keep the disease at bay.
They said a mutation of a gene that regulates tau -- a protein linked with Alzheimer's -- had a strong impact on the rate at which the disease progresses.
Drugs that interfere with this form of tau may offer a new way to keep the disease from advancing, a team from Washington University in St. Louis reported in the journal PLoS Genetics.
The team has filed for a patent, and it said the Anglo-Swedish drug company AstraZeneca (AZN.L) had an option to license it.
"People who carry this genetic marker tend to have higher tau levels at any given stage of the disease than individuals without it," Alison Goate, who worked on the study, said in a statement.
Alzheimer's, the most common form of dementia, is a fatal brain disease in which people gradually lose their memory and their ability to reason and care for themselves.
Goate's team looked at a form of the protein tau that accumulates in the brains of people with Alzheimer's disease and that can also be found in spinal fluid.
Her team looked for single letter changes in the DNA code of genes that affect tau metabolism. They studied more than 800 people and found one version of the gene that regulates tau is linked with more aggressive Alzheimer's disease.
The findings suggest that drugs that interfere with this gene variant might be able to delay the rapid progression of the disease.
'ANOTHER AVENUE'
"We do know the disease course can last anywhere from five to 20 years. If you could prevent people from declining ... and you could slow that down, then people have a longer period of time when they have good quality of life," Goate said in a telephone interview.
Most drug research in Alzheimer's has focused on blocking another protein called beta amyloid. The new finding "gives us another avenue to think of drug targets in Alzheimer's disease," she said.
Goate and others envision a cocktail of drugs targeting both proteins, much like treatments for heart disease target different pathways of that disease.
No current drugs can permanently alter the progression of Alzheimer's, which affects more than 26 million people globally.
The study, supported in part by grants from the National Institute on Aging and from AstraZeneca, can be found here:doi/10.1371/journal.pgen.1001101
A separate study by a team at the University of California, Berkeley, found that healthy people who took Pfizer's (PFE.N) Alzheimer's drug donepezil, sold under the brand Aricept, improved their ability to learn a new skill.
They said healthy people aged 18 to 35 who took the drug as part of a pilot study did much better when they were asked to track dots moving on a computer screen compared with people who took a placebo.
They said the findings, published in the journal Current Biology, could help people with learning problems such as dyslexia.
Zdroj: Reuters.com
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Argentina sells DNA as world demands more beef
Tipping the scales at more than a ton, Montecristo would yield a lot of prime Argentine steak. But ranchers are not interested in sending bulls like him to slaughter -- his semen is far more valuable.
With newly affluent consumers from Brazil to China eating more meat, Argentine ranchers are honing their centuries-old cattle-breeding traditions to meet growing global demand for semen, embryos and genetics know-how.
"We don't have to pay for advertising, people associate the word Argentina with the word beef," said Mariano Etcheverry, secretary of CABIA, a chamber that groups around 20 Argentine bovine genetics companies.
Aided by the fame of the Argentine steak, breeders say exports to Brazil, Bolivia, Uruguay and Paraguay have surged in recent years as strong economic growth in South America swells the ranks of the middle-class. Some have also found new markets in Colombia and Venezuela.
Exports of bovine semen have increased ten-fold in the last decade, in part thanks to the devaluation of the peso currency after a 2001/02 economic crisis, Etcheverry said.
But it is China's interest in bovine genetics that is rousing big hopes among breeders in Argentina, which already sends most of its soybean exports to the Asian giant.
"China is eager to buy Argentine genetics. It has a huge population and demand for meat is booming there," said Guillermo Garcia, head of Las Lilas Genetica, which lies near the country town of Duggan some 125 km (80 miles) from Buenos Aires.
Another breeding firm, Don Panos, is also in talks with Chinese investors.
"As well as genetic material, they want the technology -- the production technique, so they can do it on their own," the company's head Carlos Marietti said.
OVERALLS AND GLOVES
At Las Lilas ranch on Argentina's rolling Pampas plains, 65 breeding bulls -- called studs -- graze in individual pens divided by electric fences to stop them from fighting.
During regular "harvests," workers whisk away the semen of bulls like Montecristo in plastic containers before the animals get the chance to mount the cows paraded before them.
"It's not dangerous. The bulls are used to it," Garcia said as the workers dodge and duck between the hulking animals, wearing overalls and gloves.
Once the semen has passed quality checks, it is diluted to make up to 300 doses that are kept in liquid nitrogen and sold for around $10 each. Garcia said the price can be much higher if the animal has a good breeding record.
"A dose from a Palermo bull can fetch $50," he said, referring to a prize-winner at the country's largest annual farm show, La Rural, a showcase for the industry.
Zdroj: Reuters.com
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DNA helps turn graphene into a chemical sensor
A new chemical sensor based on just two materials, graphene and DNA,
has been unveiled by researchers in the US. The device is simple,
highly sensitive and easy to make and the scientists believe that it
could be used to make an electronic "nose" capable of sensing a variety
of molecules. Eventually, such sensors could be used in hospitals to
detect disease, at security checkpoints to pinpoint dangerous chemicals
and even by rescue teams to find lost people.
Like their biological counterparts, electronic noses are
sensitive to a large number of different molecules. To achieve this,
they usually consist of hundreds, or even thousands, of sensors on the
same chip. Each sensor reacts to a specific molecule, just like the
olfactory receptor proteins in mammal noses do. However, the need to
fabricate thousands of different sensors – and the challenges of
converting chemical reactions into electronic signals – can make
electronic noses expensive and complicated devices.
Now, A T Charlie Johnson of the University of Pennsylvania and
colleagues Ye Lu, Brett Goldsmith and Nick Kybert have come up with a
simple way of sensing chemicals by showing that the electronic
properties of DNA-coated graphene change in when exposed to certain
molecules.
Begin with graphene transistors
Graphene is a sheet of carbon just one atom thick and the team based
its devices on graphene transistors made using the standard "sticky
tape" method, which involves exfoliating individual atomic layers of
carbon from graphite. Next, the researchers thoroughly cleaned the
graphene to remove any residue on the surface that can cause unwanted
signals.
Each transistor was then soaked in a solution of a specific
sequence of single-stranded DNA, which self-assembles into a pattern on
the surface of the graphene. DNA is made from four different bases –
adenine (A); cytosine (C), thymine (T); and guanine (G) – and an example
of a sequence used is GAG TCT GTG GAG GAG GTA GTC. "We only tested a
few sequences but the number of possible sequences is essentially
endless," explained Johnson.
The researchers selected their DNA sequences based on the ability
of the sequence to work as a chemical sensitizing agent – a role very
different from the function of DNA in living organisms. Each sequence
behaves a little differently on the surface of graphene because it has a
different shape, pH and hydrophilic properties. This means that every
sequence interacts differently with different volatile organic chemicals
(VOCs).
Change in resistance
When the DNA/graphene reacts with a chemical in its environment, the
resistance of graphene changes. This change, which can be as large as
50%, can easily be measured using simple equipment. And, because this is
a direct electronic measurement, it is very fast – complete responses
can be seen in less than 10 seconds and the sensors recovers in about
30.
"By making an array of such DNA-graphene devices, we believe that
we could exploit this property of DNA/graphene to detect explosives,
chemical weapons (like nerve gas agents) or even toxic compounds that
might be accidentally released at a plant," Johnson told physicsworld.com .
"One of the great things about this research is that there is
nothing really expensive about any of the sensor components, given the
continual advances being made in graphene production," said Johnson.
Putting dogs out of business
The team's next big challenge is to scale up production of its
sensors. "We need to test more DNA sequences, fit more devices on a chip
and make sure we understand all the signals when a big array of sensors
is exposed to a mixture of chemicals," adds Johnson. "We have high
hopes for these sensors but there are still lots of hurdles to overcome.
Eventually, we would like to put dogs out of the chemical sensing
business, and with proper development, sensors like ours might be able
to do that."
Zdroj: web
zpět
DNA helps turn graphene into a chemical sensor
A new chemical sensor based on just two materials, graphene and DNA,
has been unveiled by researchers in the US. The device is simple,
highly sensitive and easy to make and the scientists believe that it
could be used to make an electronic "nose" capable of sensing a variety
of molecules. Eventually, such sensors could be used in hospitals to
detect disease, at security checkpoints to pinpoint dangerous chemicals
and even by rescue teams to find lost people.
Like their biological counterparts, electronic noses are
sensitive to a large number of different molecules. To achieve this,
they usually consist of hundreds, or even thousands, of sensors on the
same chip. Each sensor reacts to a specific molecule, just like the
olfactory receptor proteins in mammal noses do. However, the need to
fabricate thousands of different sensors – and the challenges of
converting chemical reactions into electronic signals – can make
electronic noses expensive and complicated devices.
Now, A T Charlie Johnson of the University of Pennsylvania and
colleagues Ye Lu, Brett Goldsmith and Nick Kybert have come up with a
simple way of sensing chemicals by showing that the electronic
properties of DNA-coated graphene change in when exposed to certain
molecules.
Begin with graphene transistors
Graphene is a sheet of carbon just one atom thick and the team based
its devices on graphene transistors made using the standard "sticky
tape" method, which involves exfoliating individual atomic layers of
carbon from graphite. Next, the researchers thoroughly cleaned the
graphene to remove any residue on the surface that can cause unwanted
signals.
Each transistor was then soaked in a solution of a specific
sequence of single-stranded DNA, which self-assembles into a pattern on
the surface of the graphene. DNA is made from four different bases –
adenine (A); cytosine (C), thymine (T); and guanine (G) – and an example
of a sequence used is GAG TCT GTG GAG GAG GTA GTC. "We only tested a
few sequences but the number of possible sequences is essentially
endless," explained Johnson.
The researchers selected their DNA sequences based on the ability
of the sequence to work as a chemical sensitizing agent – a role very
different from the function of DNA in living organisms. Each sequence
behaves a little differently on the surface of graphene because it has a
different shape, pH and hydrophilic properties. This means that every
sequence interacts differently with different volatile organic chemicals
(VOCs).
Change in resistance
When the DNA/graphene reacts with a chemical in its environment, the
resistance of graphene changes. This change, which can be as large as
50%, can easily be measured using simple equipment. And, because this is
a direct electronic measurement, it is very fast – complete responses
can be seen in less than 10 seconds and the sensors recovers in about
30.
"By making an array of such DNA-graphene devices, we believe that
we could exploit this property of DNA/graphene to detect explosives,
chemical weapons (like nerve gas agents) or even toxic compounds that
might be accidentally released at a plant," Johnson told physicsworld.com .
"One of the great things about this research is that there is
nothing really expensive about any of the sensor components, given the
continual advances being made in graphene production," said Johnson.
Putting dogs out of business
The team's next big challenge is to scale up production of its
sensors. "We need to test more DNA sequences, fit more devices on a chip
and make sure we understand all the signals when a big array of sensors
is exposed to a mixture of chemicals," adds Johnson. "We have high
hopes for these sensors but there are still lots of hurdles to overcome.
Eventually, we would like to put dogs out of the chemical sensing
business, and with proper development, sensors like ours might be able
to do that."
Zdroj: web
zpět
DNA helps resolve crimes of Argentina's Dirty War
Small red coffins are stacked inside a bleak office just blocks from Argentina's Congress, a chilling reminder of the thousands of people kidnapped and killed during the bloody 1976-1983 dictatorship.
Inside the boxes are the bones of recently identified victims of the so-called Dirty War, waiting to be picked up by relatives for a proper burial three decades after they were murdered by their own government.
Identifications have sped up in the last 2-1/2 years, thanks to improved DNA technology and a public campaign urging relatives of the disappeared to donate blood samples.
Forensic anthropologists have identified 120 Dirty War victims since 2007, about a third of the total identifications made in the last 27 years, enabling families to finally find closure and bring human rights abusers to justice.
French activist Yves Domergue, whose remains were identified this year, was 22 when he disappeared in 1976. His family had been looking for answers since.
"Now we can properly mourn and also begin new trials against those responsible," his brother Eric Domergue said.
Human rights groups estimate as many as 30,000 people were abducted and killed during the military dictatorship. Many were anonymously buried in local cemeteries while others were pushed from military aircraft into the sea.
"The perpetrators thought that even if we discovered the bones of the people they threw into the sea or buried in the ground, we'd never know who they were," Domergue said. "It's thanks to science that we got Yves back."
Anthropologists found Yves Domergue's body in an unmarked grave in Santa Fe province last year and matched DNA from his bones with blood samples his parents and brother provided.
Spurred by a campaign that started in 2007 and was relaunched last week, about 3,000 families have so far donated blood to a DNA database managed by the Argentine Forensic Anthropology Team, a nongovernmental
group.
"The database means the families will have the possibility of getting answers practically forever," said Luis Fondebrider, one of the team's founding members.
This week his team is sending 600 bone fragments and 900 blood samples to a private U.S. lab that helped identify victims of the 9/11 attacks on the World Trade Center, hoping their sophisticated software system will find matches.
DETECTIVE WORK
DNA technology has improved significantly over the last few years, making the identification process faster and more accurate, said Ed Huffine, an executive at the Bode Technology Group, the U.S. lab that analyzes the Argentine DNA.
Ever-smaller DNA samples can be detected and extracted from degraded remains, meaning bones that could not tell a story before, now can.
But the process of identifying victims and building a case against those responsible is an arduous one that begins long before samples are sent for costly DNA analysis.
The bones can reveal the age, sex and diseases a person suffered, but about half the Argentine Forensic Anthropology Team's work is following the paper trail.
This involves trawling through cemetery, police and military records and conducting interviews with survivors, former military officials and family members.
"It's part historian, part science, part detective work," Fondebrider said.
Without an identified body, the suspected killers cannot be put on trial for murder.
Earlier this month, Fondebrider testified in the trial of two former top army officials charged with five murders based on identifications he made.
The five identified were among eight bodies found in cement-filled drums in October 1976.
For families, it is finally knowing what happened that provides the most relief. When remains are identified, relatives are invited to the anthropologists' offices in Buenos Aires for a viewing.
"Many ask, 'How do you know this is my loved one?'" Fondebrider said. "Because they are not looking at flesh and blood ... they need to know for sure."
Zdroj: Reuters.com
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Don't stand in the way of genomes for all
A crackdown on firms selling gene tests direct to the consumer would come at a cost, argue Daniel MacArthur and Caroline Wright
AS WE enter the era of genomic medicine and affordable whole-genome sequencing, public understanding of genetics is becoming increasingly important. There are few better introductions to the complexities and uncertainties of modern genetics than allowing people to access their own DNA.
Unfortunately, recent attacks on direct-to-consumer (DTC) genetic testing by US regulators may signal a disproportionate crackdown that could limit this access. We believe that regulation is needed, but are worried that it will focus too heavily on "protecting" consumers from their own genomes.
Lauded as Time magazine's Invention of the Year in 2008, personal genome scans have attracted both international attention and criticism. They promise to provide consumers with information ranging from disease risk to ancestry, based on hundreds of thousands of common genetic markers.
Living up to that promise has been difficult. Despite the large amount of information contained in a genome scan, the medical value as of now is extremely limited. Scientists have uncovered only a fraction of the genes involved in complex diseases such as diabetes or rheumatoid arthritis, so risk prediction based on genetics alone is weak and subject to change.
However, the tests can provide potentially useful information including warnings of adverse drug reactions and the possibility of passing genetic diseases on to children, as well as recreational information such as ancestry. The industry has also created some innovative products, such as interfaces for explaining complex risk information and a new model for research in which customers can volunteer to participate in genetic studies.
Although making sense of the information is not straightforward, peering into your own genome can be a powerful education in modern genetics and epidemiology - just so long as the information provided is accurate and comprehensible.
Are DTC genetic testing companies delivering the goods? You certainly would not get that impression from the recent sabre-rattling of US regulators. In the past couple of months the industry has endured a brutal Congressional hearing in which its products were described as "snake oil", a report by the US Government Accountability Office blasting it for inconsistent results and unethical marketing, and threats from the Food and Drug Administration to regulate DTC genetics as "high risk" medical devices.
There are legitimate concerns about sections of the industry. Though some DTC genetics companies uphold high standards, at the bottom end of the market assorted disreputable operators offer products based on weak or non-existent science.
However, the US authorities are going over the top, conflating the two ends of the market and exaggerating the dangers of providing genetic information directly to consumers. The risk is that they translate their own hyperbole into heavy-handed legislation without any evidence that it is either wanted or needed.
In general we would argue that people should be free to access their own genetic data unless there is good reason to believe that doing so will cause them harm - and as long as the information is accurate and transparent.
What is needed is measured regulation that protects unwary consumers, punishes false claims and weeds out fraudsters without destroying the potential of DTC genetics to drive innovation and educate the public.
It is crucial that companies meet stringent standards for the accuracy of their data and use formally accredited laboratories to perform their analysis. They must also ensure that their customers are properly informed about the nature of the information they will receive and its implications and limitations. Customers should have access to expert advice if they want it, although medical supervision should not be a requirement to access your own genome. False advertising, misleading claims and unethical or illegal marketing should be punished.
Companies must also be transparent about the science underpinning their results. A central database of genetic tests being developed by the US National Institutes of Health would be a natural repository for this information, and submission of supporting evidence to such a database should be mandatory.
These needs could be met with minimal regulatory changes: standards for testing laboratories already exist in the US, and punishment for false advertising simply requires greater engagement by consumer watchdogs.
As the drama unfolds in the US, there are signs of a more measured response in the UK. On 4 August, the Human Genetics Commission published a "framework of principles" for DTC genetics that lays out guidelines in areas such as accuracy, consent and data protection. While the framework is non-binding, it is intended to serve as the basis for formal regulation.
We don't yet know what role personal genomics will play in the future of medicine. However, we do know that it has great potential for innovation and education, and we must ensure that neither excessive regulation nor medical paternalism get in the way.
Zdroj: New Scientist
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Vit D linked to cancer, autoimmune disease genes
Scientists have found that vitamin D influences more than 200 genes, including ones related to cancer and autoimmune diseases like multiple sclerosis -- a discovery that shows how serious vitamin D deficiency can be.
Worldwide, an estimated one billion people are deficient in vitamin D, and a team of scientists from Britain and Canada said health authorities should consider recommending supplements for those at most risk.
"Our study shows quite dramatically the wide-ranging influence that vitamin D exerts over our health," said Andreas Heger of the Functional Genomics Unit at Britain's Oxford University, who led the study.
Vitamin D effects our DNA through something called the vitamin D receptor (VDR), which binds to specific locations of the human genome. Heger's team mapped out these points and identified more than 200 genes that it directly influences.
Vitamin D deficiency is a well-known risk factor for rickets, and some evidence suggests it may increase susceptibility to autoimmune diseases such as multiple sclerosis (MS), rheumatoid arthritis and type 1 diabetes, as well as certain cancers and even dementia.
With this is mind, the group looked at disease-associated regions of the gene map to see if they had higher levels of VDR binding. They found VDR binding was "significantly enriched" in regions linked to several common autoimmune diseases, such as MS, type 1 diabetes and Crohn's disease, as well as in regions associated with cancers such as leukemia and colorectal cancer.
"SUNSHINE VITAMIN"
Sreeram Ramagopalan, of the Wellcome Trust Center for Human Genetics at Oxford University, said the results, published on Monday in the journal Genome Research, showed "just how important vitamin D is to humans, and the wide variety of biological pathways that vitamin D plays a role in."
Most Vitamin D is made by the body as a natural by-product of the skin's exposure to sunlight. It can also be found in fish liver oil, eggs and fatty fish such as salmon, herring and mackerel, or taken as a supplement.
Some experts say that up to half the world's population has lower than optimal levels of vitamin D, and that about one billion people are actually vitamin D deficient. The problem is getting worse as people spend more time indoors.
A study published in March found that vitamin D is vital for activating the immune system's killer cells, known as T cells, which remain dormant and unaware of threats from infections if vitamin D is lacking in the blood.
Ramagopalan said the latest study suggested vitamin D played a role "in susceptibility to a host of diseases" and that health authorities should consider giving supplements to pregnant women and young children as a preventative measure.
"Vitamin D supplements during pregnancy and the early years could have a beneficial effect on a child's health in later life," he wrote. "Some countries such as France have instituted this as a routine public health measure."
There are no definitive studies on the optimal daily dose of vitamin D but some experts recommend 25 to 50 micrograms.
Zdroj: Reuters.com
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Genetic signature may lead to better TB diagnosis
Scientists have found a "genetic signature" in the blood of patients with active tuberculosis (TB) and believe their discovery could help develop better diagnostic tests for the disease, as well as better treatments.
More than 2 billion people, or a third of the world's population, are estimated to be infected with the organism Mycobacterium tuberculosis (MTB) which causes TB, but the vast majority have the infection in latent form and have no symptoms.
The British scientists said they had now found a pattern of genes in the blood which is specific to up to 10 percent of those 2 billion people who develop active TB in their lungs.
The genetic signature shows the extent of the disease in the lungs and disappears after successful treatment, they said in a study in the journal Nature on Wednesday.
"Although people have been studying TB for more than a century, there is still a desperate need for better prognostic and diagnostic tests and more information about the body's response to MTB infection, which may also help in the design of vaccines and treatments," said Anne O'Garra, of the Medical Research Council, who led the study.
TB is one of the oldest diseases known to mankind and afflicts mostly the poor in developing regions such as sub-Saharan Africa, India and China. It is among the world's top 10 leading causes of death and killed 1.8 million people worldwide in 2008, or one person every 20 seconds.
Current drugs for TB are at least four decades old and must be taken for several months. Patients often fail to take the full treatment course, which has spawned drug resistant TB and made the disease more dangerous and more difficult to treat.
Doctors say current diagnostic tests for TB have barely been improved in the last 125 years.
BLOOD TEST?
O'Garra's study was conducted in London -- which has 40 percent of all British TB cases and where 3,500 people were diagnosed last year -- and then checked on a separate group of patients in Cape Town, South Africa, where TB is often found in people whose immune systems are weakened by the AIDS virus HIV.
Results showed that around 10 percent of those with latent infection also had the genetic signature for the active disease.
The scientists said it was too early to say yet whether this 10 percent would be the same 10 percent who are estimated to go on to develop active TB, but further studies were underway.
At this stage the findings are a significant step towards developing a blood test using the genetic signature to predict which people with latent TB will get sick, they said.
Robert Wilkinson, the director of Cape Town University's clinical infectious diseases unit, who also worked on the study, said such a test would enable thousands of people at risk of active TB to be diagnosed and treated earlier, and help doctors to avoid treating large numbers of patients unnecessarily.
"It's known that treatment for latent TB is effective and can contribute to TB control -- but the doctor's dilemma...is that...you are prescribing unnecessary treatment probably to 9 out of 10 people," he said in a briefing about the work.
"If there was a way of finding out who was most at risk, then that would greatly rationalise the treatment of latent TB."
Zdroj: Reuters.com
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Global Bioinformatics Market Expected to Reach $8.3 Billion by 2014
MarketResearch.com has announced the addition of MarketsandMarkets's new report "Bioinformatics Market - Advanced Technologies, Global Forecast and Winning Imperatives (2009 - 2014)" to their collection of Biotechnology market reports. For more information, visit http://www.marketresearch.com/product/display.asp?ProductID=2745333 Bioinformatics has gained high importance due to its ability to facilitate rapid clinical research, and also due to its various applications such as gene therapy and molecular science. Bioinformatics uses information technology, statistics, and algorithms to integrate biological data. Pharmaceutical companies are now adopting automated technologies to manufacture effective therapies and drugs due to increasing concerns about drug safety and the stringent regulations that govern clinical trials for drug discovery. Pharmaceutical companies have increased their focus on process improvement and quality, as the current competitive scenario offers little scope for price escalation and product differentiation. The market for bioinformatics platforms is growing at a significant pace with the increasing demand from U.S. and Europe. This trend is supported by the increasing demand for sequencing platforms with increasing life science research using techniques such as gene expression analysis, sequence analysis, and protein expression analysis. The global bioinformatics market is expected to reach $8.3 billion by 2014 at a high CAGR of 24.8% from 2009-2014. While knowledge management formed the largest submarket is 2009 at $1.3 billion, the bioinformatics platforms market is expected to have greatest market share in 2014 at an estimated $3.9 billion, due to rising demand from the U.S. and Europe.
Zdroj: Reuters.com
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Gene testing could have saved weight-loss drug
Genetic testing might have helped identify people who would become depressed or suicidal while taking Sanofi-Aventis' (SASY.PA ) weight loss drug Acomplia, which might have helped keep the drug on the market, U.S. researchers said on Thursday.
They said partial results from a study of the drug in which five people committed suicide confirmed that it increased the risk of psychiatric side effects.
The study was halted in 2008 and the company pulled the drug from the market in Europe, but the researchers think genetic testing might have been able to identify people who were at risk of the side effects, and rescue the once-promising treatment, said Dr. Eric Topol of Scripps Translational Science Institute in La Jolla, California, whose study appears in the journal Lancet.
Acomplia, known generically as rimonabant, blocks the same reward receptors in the brain that become active during marijuana use, and for some people, it caused serious bouts of anxiety and depression that led to suicide.
"Finding the gene for severe adverse drug reactions is a lot easier than we ever thought it would be," Topol said in a telephone interview.
Topol thinks if they had thought to collect genetic information on the study's more than 18,000 participants, they might have spared the drug.
"We probably could have figured out genomically who was susceptible and that drug could be quite viable," Topol said in a telephone interview.
Hopes had been high for Acomplia, which not only helped people lose weight but helped them achieve more normal blood sugar levels and improvements in blood fats known as triglycerides and HDL cholesterol, the so-called good cholesterol.
In Topol's study, which looked at the heart benefits of the drug, four patients taking rimonabant and one person taking a placebo committed suicide.
Of the results they had, they found deaths from heart disease, heart attacks and strokes occurred at similar rates in both groups, and they did find that serious psychiatric side effects were increased in rimonabant users compared with placebo.
Due to these side effects, the European Medicines Agency recommended doctors no longer prescribe rimonabant from October 2008. Concerns about side effects prevented the drug from winning U.S. regulatory approval.
Topol says it is likely too late to revive Acomplia, but he said the study does offer insights about how to avoid similar problems with drugs in the future.
"Genomics could potentially be used to pre-empt use of the drug in individuals with risk of serious adverse events," he said in a statement.
Zdroj: Reuters.com
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Argentine lake may offer clues to life on Mars
A lake in Argentina's remote, inhospitable northwest may offer clues on how life got started on Earth and how it could survive on other planets, scientists say.
Researchers have found millions of "super" bacteria thriving inside the oxygen-starved Lake Diamante, in the center of a giant volcanic crater located over 15,400 feet above sea level.
The bacteria's habitat is similar to primitive earth, before living and breathing organisms began wrapping a protective atmosphere of oxygen around the planet.
The conditions -- which include high arsenic and alkaline levels -- could also shed light on life beyond Earth.
"This is of great scientific interest as a window to look to our past and also for a science called astrobiology, the study of life on other planets," said Maria Eugenia Farias, part of the team that discovered the life-forms in Lake Diamante earlier this year.
If bacteria can survive here, the theory goes, it could also survive somewhere like Mars.
So-called "extremophiles" have been found in other parts of the world -- and they can have significant commercial value. Bacteria that break down lipids are used in detergents for example.
But Farias said these bacteria, called "polyextremophiles" are exceptional because they flourish in the harshest of circumstances.
"What we have here is a series of extreme conditions all in one place. And this is what makes this place unique in the world," said Farias, a microbiologist at the National Scientific and Technical Research Council in Tucuman province.
The lake sports levels of arsenic 20,000 times higher than the level regarded as safe for drinking water and its temperature is often below freezing. But because the water is so salty -- five times saltier than sea water -- ice never forms.
The bacteria's DNA mutates to survive the ultra-violet radiation and low oxygen levels found at such high altitudes, which could make it of interest to the pharmaceuticals industry, Farias said. It could also have future commercial applications in products such as sunscreens, she added.
Farias and her team are looking for Argentine funding to produce a metagenome of the bacteria, an advanced study which provides a DNA sequence of the entire microbe colony.
This would enable her crew to study the bacteria in Argentina and help ensure that the South American country keeps hold of potentially lucrative patents for new antioxidants or enzymes that could be derived from the bacteria.
Zdroj: Reuters.com
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Stem cells may hold key for fatal skin disease
High-risk bone marrow transplants partially cured five children with a potentially deadly genetic defect in which proteins that hold layers of skin together are absent, U.S. researchers said Wednesday.
But one other child died from side effects of a drug used to prepare for a transplant and a second died from a post-transplant infection.
People with recessive dystrophic epidermolysis bullosa, or RDEB, are plagued by painful blisters on the skin, mouth and throat, caused by the slightest trauma that can expose the body to infection and, in some cases, an aggressive form of cancer.
With the new treatment, "there was improved healing, fewer blisters, and their quality of life was positively affected. They could do things they couldn't do before, like ride a bicycle or go on a trampoline," said Dr. John Wagner of the University of Minnesota, who worked on the study.
It was published in the New England Journal of Medicine.
In addition, the patients' improvement progressed with time, he said. All five children who survived showed improvement within 100 days, although the pace varied widely, he said in a telephone interview.
Because of the high risks involved in bone marrow transplants, only the sickest patients with the rare condition -- affecting 1 in 50,000 -- have been considered candidates for a transplant, Wagner said.
Wagner reported on results of the first seven attempts, which took place at the University of Minnesota Amplatz Children's Hospital. Six other children have subsequently been treated with good results, he said.
Researchers are now trying to isolate the cells of the bone marrow best able to fix the defect and join layers of skin.
HIGH COST
The treatment, including the cost of the transplant, is between $500,000 to $1 million. But routine care for children with the collagen defect already costs about $30,000 a year and can rise due to frequent hospitalizations and complications of the disease.
"These kids have horrible pain, chronic infections of the skin, multiple hospitalizations, and systemic infections," Wagner said.
"They frequently can't eat or refuse to eat because of the pain. Often they die of chronic malnutrition and chronic blood loss."
Dr. Jakub Tolar, also of the University of Minnesota, said the treatment was unique because it showed that the effects of a bone marrow transplant can extend beyond the blood.
"What we have found is that stem cells contained in bone marrow can travel to sites of injured skin, leading to increased production of collagen, which is deficient in patients with RDEB," Tolar, who worked on the study, said in a statement.
Dr. Lenna Bruckner-Tuderman of University Medical Center in Freiburg, Germany , said in a commentary that the therapy represented a leap forward but expressed caution.
Because the disease can wax and wane, "it is difficult to determine how much of the clinical improvement in the children was due to transplantation and how much was due to a long period of careful medical attention, protection from trauma, and standardized wound care," Bruckner-Tuderman said.
Zdroj: Reuters.com
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FBI laboratory has large backlog of DNA cases
The FBI's laboratory has a backlog of more than 3,200 forensic DNA cases, which can prevent timely capture of criminals and prolong incarceration of innocent people, according to a U.S. Justice Department report released on Monday.
The report by the department's inspector general said the backlog, which has increased sharply in the past year, can cause delays in legal proceedings that must await DNA analysis results.
The DNA evidence typically comes from forensic samples from crime scenes or from such items as clothing, envelopes and drinking glasses.
Of the backlog, more than 2,700 cases are in the laboratory unit that primarily examines biological fluid stains, such as blood and semen. Nearly 500 cases are in the unit that analyzes evidence such as hair, bones, and teeth.
The report said the delays can prolong the incarceration of innocent people who could be exonerated by DNA evidence and can adversely affect families of missing persons waiting for positive identification of remains.
The time it takes to receive the FBI laboratory results varies from about 150 days to more than 600, depending on the type of DNA evidence submitted for analysis.
The FBI has adopted a number of measures in an effort to reduce the backlog and minimize laboratory bottlenecks, the report said.
The FBI is in the process of adding 17 additional forensic examiners, but their hiring and training could take as long as 18 months.
The backlog of cases has been considered a problem for a number a years, as the federal law enforcement agency seeks to come up with an electronic evidence tracking system, according to the report.
Zdroj: Reuters.com
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Regulation could save genome scanning, not kill it
ARE we witnessing the beginning of the end of "personal genomics"? After a bruising hearing in the US Congress last week, and with the Food and Drug Administration flexing its regulatory muscles, that is what some commentators predict. "There's no question that the sheer scale and ferocity of this combined inquisition from the FDA and Congress will forever change the face of the personal genomics landscape," wrote Daniel MacArthur in his Genetic Future blog, predicting "excessive, innovation-crushing regulation". But this doesn't have to be the end of the industry. If it embraces sensible regulation, then it has the chance to shift personal genomics from a minority recreational pursuit to the heart of clinical medicine. We all stand to benefit from such a shift, by being prescribed drugs that work better for our particular genetic make-up, for example. The star turn at last week's congressional hearing was a report from the US Government Accountability Office (GAO) in which investigators recounted their experience of submitting samples for DNA testing to the four leading personal genomics companies - 23andMe, DeCode Genetics, Navigenics and Pathway Genomics. Like others who have had their genomes scanned by different firms, the GAO investigators obtained varying predictions of their risks of developing common diseases. This is not surprising, given that the companies use different combinations of genetic markers and different algorithms to make predictions from these markers. More damning was a compilation of the conversations between undercover GAO investigators and representatives of genetic testing firms, including two of the personal genomics companies. Congress heard evidence that a Navigenics sales rep offered ill-informed advice on the genetics of breast cancer. And while New Scientist warned last year of the potential for genome scans to be abused by people submitting samples from others obtained without their consent, Congress heard that one of Pathway's sales team actually encouraged someone to send in a sample from her fiancé for testing for disease risks without his knowledge. Some form of regulation is clearly needed. If it is not too heavy-handed, the FDA's involvement could help move the industry into the mainstream. Genome scans could be useful in predicting a person's response to commonly used drugs, helping to determine, for example, the optimum dose they should receive. If so, then FDA involvement will be crucial as drug labels will need to indicate how prescriptions should be modified in the light of genetic information. The future for the personal genomics industry may lie in working with doctors and health insurers to test patients and help improve clinical practice. Navigenics is already working primarily through doctors. Given the limited number of people interested in having their genomes scanned for curiosity's sake - just a few tens of thousands are thought to have purchased scans so far - simple economics may send others down the same path
Zdroj: New Scientist
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Consumer gene test results misleading
People who send off their saliva to genetic testing companies to find out their risk for prostate cancer or diabetes are likely to get different results, depending on the company they choose, government investigators told lawmakers on Thursday.
Their undercover investigation of four unnamed genetic testing companies, in which five people sent away their DNA for testing, showed that the tests produced inconsistent results for the same disease 68 percent of the time.
Four out of five donors got test results that conflicted with their actual medical conditions and family histories.
The tests the GAO studied ranged from $300 to $1,000.
"Assuming these tests are credible, one would expect that identical DNA would receive identical predictions," Gregory Kutz of the Government Accountability Office said in prepared testimony before a U.S. House of Representatives panel investigating direct-to-consumer genetic tests.
Kutz told the panel, a subcommittee of the House Committee on Energy and Commerce, that the test companies use deceptive marketing practices and said the results "are misleading and of little use to consumers."
Dr. Jeffrey Shuren, director of the Center for Devices and Radiological Health at the U.S. Food and Drug Administration, said his agency is preparing to regulate the sale of these tests, which are offered by companies such as Navigenics Inc, Pathway Genomics Corp and 23andMe Inc, which is backed by Google Inc.
Shuren said the agency has sent letters to Pathway Genomics, Knome Inc, Navigenics Inc, deCODE Genetics and 23andMe -- all of which have been selling their tests directly to consumers -- informing them of the move to regulate them.
MEDICAL DEVICE
He said products by all five of these companies, in his view, meet the definition of a medical device, based on the companies' claims about their test results.
For more than three decades, the FDA has chosen not to regulate simple diagnostic tests developed in individual laboratories. But it does regulate tests considered medical devices -- which are used to diagnose disease or other conditions or to prevent disease.
This week, the FDA hosted a two-day meeting with experts and companies about how the agency should begin regulating lab-developed tests.
Shuren said the FDA plans to draft a framework for regulating lab-developed tests, which it will phase in based on the level of risk to patients.
None of the genetic tests now offered directly to consumers has been cleared by the FDA to ensure the results are "accurate, reliable and clinically meaningful," he said.
Shuren said the FDA has also sent a letter to Illumina Inc, a maker of genetic testing equipment, for "supplying unapproved reagents and instrumentation" labeled for research purposes to direct-to-consumer testing companies.
All six companies have been asked to meet with the FDA to discuss the regulatory status of their products.
23andMe Inc said in a statement that the GAO had refused to discuss its report with the company.
"We are confident in our service's accuracy, reliability and value. However, we embrace the ideas that the FDA offered today and look forward to helping to develop a regulatory framework that provides standards and transparency across the industry," it said.
Shuren said the FDA has been watching the activity of companies selling genetic tests directly to consumers for some time, but grew concerned with the "aggressive" marketing practices of Pathway Genomics, which had announced a pact with Walgreen Co in April to distribute its tests through its network of more than 6,000 neighborhood pharmacies.
Pathway has since stopped selling its tests directly to consumers.
Representatives from Pathway, 23andMe and Navigenics defended their tests before the panel, saying they are useful in helping consumers change their habits to help avoid problems like diabetes.
But Dr. James Evans of the University of North Carolina, who advised the GAO, told the panel they are of little use to consumers.
"No one knows how to interpret these data. That is quite clear," he said.
Zdroj: Reuters.com
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Affymetrix Launches Axiom Custom Genotyping Arrays Utilizing World`s Largest Validated SNP Database
Affymetrix, Inc. (NASDAQ:AFFX) today announced that it has launched Axiom Custom Genotyping Arrays, the newest addition to the Axiom Genotyping Solution. Researchers can now leverage Affymetrix` Axiom Genomic Database, the world`s largest collection of validated common and rare SNPs, to create custom arrays containing 50,000 to as many as 2.6 million SNPs. This inherent flexibility allows researchers to conduct genome-wide association, replication, fine mapping, and candidate gene studies on a single platform. Axiom Custom Genotyping Arrays deliver unparalleled flexibility in study design and maximize researchers` ability to generate meaningful data with the most relevant SNPs for their disease or cohort. Scientists can now create extremely precise array designs leveraging Affymetrix` Genomic Database, which includes 7.4 million SNPs from the 1000 Genomes Project, the International HapMap Project, and other sources. With more than 5 million validated SNPs, including more than 600,000 novel 1000 Genomes Project SNPs with a minor allele frequency (MAF) of less than 2.5 percent, the Axiom Genomic Database will enable researchers to study the role of rare variants in human disease by designing arrays with markers in specific MAF bins of their choice. Researchers can also combine SNPs from their own sequencing projects and other sources with Affymetrix` validated SNPs to design arrays with up to 2.6 million SNPs. In the near future, this capability will expand to support custom array designs containing more than 5 million SNPs. As large-scale genotyping studies begin to leverage newly discovered content, a large number of researchers are now interested in low-frequency variants and genetic diversity in a variety of populations, particularly Africans. Both of these trends signal the need for higher density arrays and the ability to customize content to maximize coverage in the population of interest. "Affymetrix` new custom offering addresses new trends in genetic research by allowing a significant amount of flexibility," said Jay Kaufman, Vice President of DNA Product Marketing at Affymetrix. "Researchers can now create arrays consisting of 50,000 SNPs for focused or replication studies, a multi-sample array plate of millions of low-frequency variants, or an array tailored to the sample cohort being studied. This new multifaceted custom option will also enable scientists to quickly leverage the most recent and novel content as SNP discovery continues." Researchers designing Axiom Custom Genotyping Arrays will receive design support and expertise from the Affymetrix team of bioinformatics scientists to ensure streamlined SNP selection and intelligently designed arrays that fulfill the objectives of their study. Customers can also screen a representative subset of their sample cohort against approximately 5 million validated SNPs to gain valuable insights into linkage disequilibrium (LD) structure, minor allele frequency information, and assay performance to assist in the design of their custom array. This one-of-a-kind selection and design process provides another valuable tool for researchers to design highly optimized genotyping arrays based on empirical data rather than speculative marker selection. This database screening service is available through the Affymetrix Research Services Laboratory. "As the needs of human disease research evolve with the rapid expansion of available markers, customization and flexibility have become increasingly important," said Kevin King, President and CEO of Affymetrix. "Researchers want to design studies to optimize their ability to answer key biological questions. Axiom Custom Genotyping Arrays enable them to do this with a wide range of formats, relevant content, and high-quality data to expedite their disease association studies." To learn more about Axiom Custom Genotyping Arrays, please visit www.affymetrix.com/axiom. About Affymetrix Affymetrix technology is used by the world`s top pharmaceutical, diagnostic, and biotechnology companies, as well as leading academic, government, and nonprofit research institutes. More than 1,900 systems have been shipped around the world and more than 21,000 peer-reviewed papers have been published using the technology. Affymetrix is headquartered in Santa Clara, Calif., and has manufacturing facilities in Cleveland, Ohio, and Singapore. The company has about 1,000 employees worldwide and maintains sales and distribution operations across Europe and Asia. For more information about Affymetrix, please visit www.affymetrix.com. Forward-looking statements All statements in this press release that are not historical are "forward-looking statements" within the meaning of Section 21E of the Securities Exchange Act as amended, including statements regarding Affymetrix`"expectations," "beliefs," "hopes," "intentions," "strategies," or the like. Such statements are subject to risks and uncertainties that could cause actual results to differ materially for Affymetrix from those projected. These and other risk factors are discussed in Affymetrix` Form 10-K for the year ended December 31, 2009, and other SEC reports for subsequent quarterly periods. NOTE: Affymetrix, the Affymetrix logo, and Axiom are trademarks or registered trademarks of Affymetrix, Inc. Affymetrix, Inc. Annette Summers, 408-731-5169 Senior Director, Marketing Communications Annette_Summers@affymetrix.com Doug Farrell, 408-731-5285 Vice President, Investor Relations
Zdroj: Reuters.com
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Mother's diet, genes raise birth defect risk: study
Mothers who eat a high fat diet before and during pregnancy may be putting their offspring at risk of birth defects, scientists said on Tuesday.
British researchers studying mice found that a pregnant mother's diet may interact with the genes her unborn baby inherits and influence the type or severity of birth defects such as congenital heart disease and cleft palate.
"These are very important findings as we have been able to show for the first time that gene-environment interactions can affect development of the embryo in the womb," said Jamie Bentham of the Wellcome Trust Center for Human Genetics at the Oxford University, who led the study.
"We know that poor diet and defective genes can both affect development, but here we have seen the two combine to cause a much greater risk of developing health problems and more severe problems. We are excited by this as it suggests that congenital heart defects may be preventable by measures such as altering maternal diet," he said in a statement about the findings.
Congenital heart disease is the most common form of birth defect, and previous studies have shown that children born to mothers who have diabetes or who are overweight have an increased risk of it.
It is also known that certain genetic changes -- such as deficiency in Cited2 -- can give rise to congenital heart disease, but until now scientists did not know if external factors such as a mother's diet could interact with genetic changes to affect their babies.
The British researchers, whose findings were published in the journal Human Molecular Genetics, compared healthy mice with those lacking a gene called Cited2.
Cited2 deficiency results in heart defects in mice and in humans and can also lead to a serious type of heart defect called atrial isomerism, where the left-right asymmetry of the heart is disturbed.
Researchers fed the mice a high fat diet before and during pregnancy and then studied the development of their babies using magnetic resonance imaging. The results were compared to mice from a second group who were fed a balanced diet.
Among offspring mice that were deficient in Cited2, the risk of atrial isomerism more than doubled, the researchers found, and the risk of cleft palate increased more than seven-fold when the mothers were fed a high fat diet.
The changes did not happen in the genetically normal offspring of mothers who had a high fat diet, suggesting that it is the combination of high fat diet and the genetic defect that is responsible, they said.
Jeremy Pearson, associate medical director of the British Heart Foundation charity, which part-funded the study, said the findings could shed light on human birth defects.
"This research shows that diet during pregnancy can directly affect which genes get switched on in unborn offspring. The study was with mice, but a similar link may exist in humans, leading to some cases of congenital heart disease."
He said the research reinforced the need for pregnant women to have a balanced diet and avoid eating too much fatty food.
Zdroj: Reuters.com
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Gene pattern predicts who will live the longest
Researchers have found a pattern of genes that predicts with more accuracy than ever before who might live to be 100 or older -- even if they have other genes linked with disease.
Their findings, published in Friday's issue of the journal Science, offer the tantalizing possibility of predicting who might hope for a longer life. They also cast doubt on the accuracy of tests being marketed now that offer to predict a person's risk of chronic diseases such as Alzheimer's.
Several teams of researchers have identified gene patterns linked with extreme old age. But the researchers led by Paola Sebastiani and Dr. Thomas Perls at Boston University say theirs provides the best accuracy yet.
They studied more than 1,000 people who lived to be 100 or more and matched them to 1,200 other people to identify the genetic patterns more common in the 100-year-olds using an approach called a genome-wide association study
To their surprise, the longest-lived people had many of the same genes linked with diseases as everyone else. Their old-age genes appeared to cancel out the effects of the disease genes.
"A lot of people might ask, 'well who would want to live to 100 because they think they have every age-related disease under the sun and are on death's doorstep, and certainly have Alzheimer's', but this isn't true," Perls told reporters in a telephone briefing.
"We have noted in previous work that 90 percent of centenarians are disability-free at the average age of 93. We had long hypothesized that to get to 100 you have to have a relative lack of disease-associated variants. But in this case, we're finding that not to be the case."
NO FREE PASSES
They identified 19 patterns among about 150 genes and said these patterns predicted with 77 percent accuracy who would be in the extreme old-age group.
"Some signatures correlate with the longest survival, other signatures correlate with the most delayed age of onset of age-related diseases such as dementia or cardiovascular disease or hypertension," Sebastiani said.
The researchers stressed that having these genes is unlikely to give a person a free pass to smoke, drink and overeat.
Sebastiani said Seventh Day Adventists have an average life expectancy of 88, eight years more than their average U.S. contemporaries.
"They get there by virtue of the fact that they have a religion that asks them to be vegetarian, they regularly exercise, they don't drink alcohol, they tend to manage their stress well through religion and time with family and they don't smoke," she said. "It really does speak to the incredible importance of lifestyle factors."
The Boston researchers said they do not plan to market a test for the long-life genes and are working to design a free website where people who have had their DNA sequenced can check and see if they have any of them.
"The methodology that we developed can be applied to other complex genetic traits, including Alzheimer's disease, Parkinson's, cardiovascular disease and diabetes," Sebastiani said.
Currently about 1 in 6,000 people live to be 100 and 1 in 7 million makes it to 110. The researchers said beliefs that certain populations in places such as Russia or Azerbaijan are more likely to have centenarians have been shown to be untrue.
Perls said he does not see the findings leading to youth elixirs, but hopes they may be used to help delay the start of age-related diseases like Alzheimer's.
Zdroj: Reuters.com
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Genetic Secrets of Living to 100
A massive genetic study of people who lived for more than 100 years has found dozens of new clues to the biology of aging.
The findings won’t be turned overnight into longevity elixirs or lifespan tests, nor do they untangle the complex interactions between biology, lifestyle and environment that ultimately determine how long — and how well — one lives.
But they do offer much-needed toeholds for scientists studying the basic mechanisms of aging, which remain largely unexplained.
“It shows that genetics plays an extremely important role at these extreme ages. And it begins to be a not-unsolvable puzzle,” said Boston University gerontologist Thomas Perls. “If we start looking at these genes and what they do, we better understand the biology of extreme longevity.”
Published July 2 in Science , the findings come from gene tests of 801 people enrolled in the Perls-founded New England Centenarian Study, the largest study in the world of people who’ve lived past 100.
People who’ve reached that mark tend to have lives that are not only exceptionally long, but unusually healthly. Unlike most people, they rarely develop diseases of aging — such as heart disease, metabolic disease, cancer and dementia — until well into their 90s. They’re also more likely to bounce back from disease, rather than entering a spiral of declining health.
That manner of aging is a goal for most people, and a public health necessity. Modern medicine has had success in slowing individual aging diseases, but when one is postponed another soon emerges. Americans are living longer but not healthier. Nearly three-quarters of U.S. health spending now goes to treating diseases of aging. That proportion is rising.
In the last decade, scientists using animal models of disease have identified numerous genes and biological pathways implicated in aging. That animal research is valuable, but the gold standard of longevity science involves long-lived people.
Other studies suggest that whether or not someone lives to their 80s is mostly a result of common-sense lifestyle choices: moderate drinking, no smoking, plenty of exercise, a vegetable-centric diet and low stress. But beyond that, “genetics plays a stronger and stronger role,” said Perls. The concentrations of telltale gene profiles found by his group suggest “that the genetic influence is very, very strong.”
Perls’ team surveyed the genomes of 801 centenarians, focusing on “hot spots” where people are most likely to have mutations. They compared the results to genome scans of 926 random people from the general population. From this came a list of 70 gene mutations found mostly in the centenarians. After comparing those to genome scans of 867 people with Parkinson’s disease, the list was whittled down to 33 key mutations.
The researchers used these results to develop statistical models of longevity-associated gene profiles. Used to evaluate anonymized sample genomes, the model could predict whether the sample came from a centenarian with 77 percent accuracy, underscoring the importance of genetics in extreme long life.
Centenarians also tended to fit one of 19 different gene profiles. Some of the profiles tracked with especially low rates of cardiovascular disease, dementia and hypertension or diabetes, suggesting specific genetic pathways for those diseases.
Perls emphasized that the profiles — which came from Caucasians, and are likely different in other ethnic groups — are not intended as guides for drug cocktails or diagnostic tests.
“We’re quite a ways away still in understanding what pathways governed by these genes are involved, and how the integration of these genes, not just with themselves but with environmental factors, are all playing a role in this longevity puzzle,” he said in a press conference.
Other were excited about the findings, but echoed Perls’ restraint.
National Institutes on Aging neuroscientist Donald Ingram called the study a “very impressive genetic and statistical tour de force,” but one that leaves environmental influences unexplained.
According to Perls, one of the study’s most intriguing results is that roughly 15 percent of the general population has some of the longevity-associated genes. Yet only one in 6,000 people currently live to be centenarians — many fewer people than seems to be suggested by the genetics.
Some of the discrepancy can likely be attributed to standards of infant care and public health at the beginning of the 20th century, when these centenarians were born, said Perls. Lifestyle and genetics are also sure to play a part. There will also be genetic factors missed by the study’s narrow focus on hot spots.
According to Jackson Laboratory gerontologist David Harrison, who called the findings “very interesting,” researchers will use animals to explore the roles of genes and pathways flagged in the study.
The findings will also need to be replicated and expanded in more human studies, said National Institutes on Aging gerontologist Winifred Rossi.
“It’s groundbreaking work,” she said. “But science is not fast. It’s slow. It takes a lot of steps to get to something with an impact. We’re only at the start of exploring longevity.”
Zdroj: Reuters.com
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Nutrients may be why some smokers avoid cancer
Smokers who have higher levels of vitamin B6 and certain essential proteins in their blood have a lower risk of getting lung cancer than those deficient in these nutrients, according to study by cancer specialists.
Scientists at the International Agency for Research on Cancer (IARC) said that although they had not found a causal link, the results may be a clue to why some smokers never get lung cancer and some non-smokers or former smokers do.
Lung cancer is the most common form of the disease in the world and 90 percent of all cases are caused by cigarette smoking. It kills 1.2 million people a year.
About 10 to 15 percent of smokers develop lung cancer -- although they often die of other smoking-related causes like heart disease, stroke or emphysema. Lung cancer is also known to kill people who never smoked or who gave up years ago.
The IARC study, which looked at around 900 people with lung cancer, found a link to low levels of vitamin B6 and an amino acid called methionine, found in protein like meat, fish and nuts. B6 is also found in meat, nuts, vegetables and bananas.
"What we have found is that these two things are strong markers of lung cancer risk, but we have not shown they are causing that rise in risk," said Paul Brennan of the Lyon-based IARC, who led the study and published its findings in the Journal of the American Medical Association (JAMA) on Tuesday.
"This indicates that diet may have an important role in lung cancer development, but it's still a little premature to say simply that if you change your diet and eat more foods with these vitamins then you'll change your future lung cancer risk."
NUTRIENTS KEY TO DNA HEALTH
Brennan's team studied around 900 lung cancer patients, mostly smokers but also including about 100 who never smoked and 260 who had quit.
Brennan said the change in risk of lung cancer linked to B6 and methionine levels was the same for all three groups, although of course the overall risk of getting the disease was much higher in the smokers to start with.
"For the two nutrients together, the risk reduction was about 60 percent," he said. "Obviously if you had a very high risk because you smoke, then a 60 percent reduction of that is quite important, although not as important as quitting smoking."
Brennan said his findings appeared to reinforce previous research which suggested deficiencies in B vitamins may increase the probability of DNA damage and subsequent gene mutations.
A Swedish study in 2005 found that women with high levels of vitamin B6 had a lower risk of developing colorectal cancer.
"Basically, these B vitamins and nutrients are all involved in the pathway which is responsible for the creation and maintenance of DNA," Brennan said. "So obviously you would want that pathway to work as well as possible."
Zdroj: Reuters.com
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U.S. gene study reveals toll of heavy smoking
Heavy smokers who get lung cancer may have tens of thousands of genetic mutations, U.S. researchers said on Wednesday.
A team at Roche's biotechnology unit Genentech in California compared all the genetic changes in a single patient's lung tumor with healthy tissue from the patient, a 51-year-old man who had smoked an average of 25 cigarettes per day for 15 years before the tumor was removed.
What they found were as many as 50,000 genetic mutations.
"Fifty thousand is a huge number. No one has ever reported such a high number," said Zemin Zhang of Genentech, whose findings appear in the journal Nature.
"This is likely associated with the smoking history of the patient. It is very alarming," Zhang said in a telephone interview.
Smoking is the biggest single cause of lung cancer, and studies suggest mutations occur with each cigarette smoked.
Zhang said the ratio between the number of cigarettes the person smoked before his tumor was removed and the number of mutations in the tumor suggest that for every three cigarettes he smoked, one genetic mutation occurred.
"It's a lot more complicated than that," Zhang said, noting that there are DNA repair mechanisms in the body that help protect against the damage of smoking, but these become less efficient over time.
Zhang said the team was so surprised by the findings they made extra checks to see if they got it wrong. They also looked for anything unusual about the smoker whose tumor they studied. "There is nothing unusual about this sample," he said.
The findings may be sobering for those contemplating taking up smoking. "If you imagine over a lifetime you are going to develop this many mutations in the genome, some people may think twice about it," he said.
ADVANCES IN GENE SEQUENCING
The study was made possible by advances in gene sequencing technology that allows researchers to look at entire genomes, rather than searching for a handful of genes that appear to be especially important in certain cancers.
This new way of studying cancer is painting a much more complex picture of the disease.
For example, the team discovered areas of the genome needed to make proteins -- which are important for cell survival -- had far lower rates of mutations, suggesting these areas are better protected, Zhang said.
But he noted the findings only reflect one man's genome. "Obviously, we'd love to have multiple fully sequenced genomes in multiple tumors," he said.
However, it already offers a much broader view of the genetic changes in lung cancer.
The price of sequencing an entire genome is falling rapidly. The latest machines from companies like Illumina and Life Technologies Corp can map out a patient's entire DNA code for as little as $5,000.
Many companies are developing machines that can do the job for $1,000.
Zhang said his team worked with a private company called Complete Genomics in Mountain View, California. "I think this provides a preview of what whole genome sequencing can tell us about the cancer genome," he said.
Zdroj: Reuters.com
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Craig Venter creates synthetic life form
Craig Venter and his team have built the genome of a bacterium from scratch and incorporated it into a cell to make what they call the world's first synthetic life form.
Scientists have created the world's first synthetic life form in a landmark experiment that paves the way for designer organisms that are built rather than evolved.
The controversial feat, which has occupied 20 scientists for more than 10 years at an estimated cost of $40m, was described by one researcher as "a defining moment in biology ".
Craig Venter , the pioneering US geneticist behind the experiment, said the achievement heralds the dawn of a new era in which new life is made to benefit humanity, starting with bacteria that churn out biofuels, soak up carbon dioxide from the atmosphere and even manufacture vaccines.
However critics, including some religious groups, condemned the work, with one organisation warning that artificial organisms could escape into the wild and cause environmental havoc or be turned into biological weapons. Others said Venter was playing God.
The new organism is based on an existing bacterium that causes mastitis in goats, but at its core is an entirely synthetic genome that was constructed from chemicals in the laboratory.
The single-celled organism has four "watermarks" written into its DNA to identify it as synthetic and help trace its descendants back to their creator, should they go astray.
"We were ecstatic when the cells booted up with all the watermarks in place," Dr Venter told the Guardian. "It's a living species now, part of our planet's inventory of life."
Dr Venter's team developed a new code based on the four letters of the genetic code, G, T, C and A, that allowed them to draw on the whole alphabet, numbers and punctuation marks to write the watermarks. Anyone who cracks the code is invited to email an address written into the DNA.
The research is reported online today in the journal Science .
"This is an important step both scientifically and philosophically," Dr Venter told the journal. "It has certainly changed my views of definitions of life and how life works."
The team now plans to use the synthetic organism to work out the minimum number of genes needed for life to exist. From this, new microorganisms could be made by bolting on additional genes to produce useful chemicals, break down pollutants, or produce proteins for use in vaccines.
Julian Savulescu , professor of practical ethics at Oxford University, said: "Venter is creaking open the most profound door in humanity's history, potentially peeking into its destiny. He is not merely copying life artificially ... or modifying it radically by genetic engineering. He is going towards the role of a god: creating artificial life that could never have existed naturally."
This is "a defining moment in the history of biology and biotechnology", Mark Bedau , a philosopher at Reed College in Portland, Oregon, told Science.
Dr Venter became a controversial figure in the 1990s when he pitted his former company, Celera Genomics , against the publicly funded effort to sequence the human genome, the Human Genome Project . Venter had already applied for patents on more than 300 genes, raising concerns that the company might claim intellectual rights to the building blocks of life.
Zdroj: Guardian UK
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"Digital genome" safeguards dying data formats
In a secret bunker deep in the Swiss Alps, European researchers have deposited a "digital genome" that will provide the blueprint for future generations to read data stored using defunct technology.
Accompanied by burly security guards in black uniforms, scientists carried a time capsule through a labyrinth of tunnels and five security zones to a vault near the slopes of chic ski resort Gstaad.
The sealed box containing the key to unpick defunct digital formats will be locked away for the next quarter of a century behind a 3-1/2 tonne door strong enough to resist nuclear attack at the data storage facility, known as the Swiss Fort Knox.
"Einstein's notebooks you can take down off the shelf and read them today. Roll forward 50 years and most of Stephen Hawking's notes will likely only be stored digitally and we might not be able to access them all," said the British Library's Adam Farquhar, one of two computer scientists and archivists entrusted with transferring the capsule.
The capsule is the culmination of the four-year "Planets" project, which draws on the expertise of 16 European libraries, archives and research institutions, to preserve the world's digital assets as hardware and software is superseded at a blistering pace.
"The time capsule being deposited inside Swiss Fort Knox contains the digital equivalent of the genetic code of different data formats, a 'digital genome'," said the grey-bearded Farquhar, coordinator of the 15 million-euro ($18.49 million) project.
"I can't even read my own dissertation anymore except in paper form, because we didn't have anything like this when I wrote it," he said.
Around 100 GB of data -- equivalent to 24 tonnes of books -- has already been created for every single individual on the planet, ranging from holiday snaps to health records, project organizers said, adding this amounted to over 1 trillion CDs worth of data across the globe.
But as technological breakthroughs help people to live longer, the lifespan of technology gets shorter, meaning the European Union alone loses digital information worth at least 3 billion euros every year, they said.
Studies suggest common data storage formats like CDs and DVDs only last 20 years, while digital file formats have a life expectancy of just five to seven years. Hardware even less.
"Unlike hieroglyphics carved in stone or ink on parchment, digital data has a shelf life of years not millennia," said Andreas Rauber, a professor at the University of Technology of Vienna, which is a partner in the project.
"Failure to implement adequate digital preservation measures now could cost us billions in the future," Rauber said, adding that the project had made open-use software available online to enable people to decipher data stored in defunct formats.
Without supporting software and compatible operating systems, knowing what is on a disc, let alone reading the files will be impossible, Farquhar said.
The project hopes to preserve "data DNA", the information and tools to access and read historical digital material and prevent digital memory loss into the next century.
"If we can nail the next 100 years, we figure we will be able to nail the next 100 years as well," Farquhar said.
This could have uses for countless different organizations, from pharmaceutical companies trying to access test data decades from now or aerospace companies checking design details of planes built to fly for 30 or 40 years.
People will be puzzled at what they find when they open the time capsule, said Rauber.
"In 25 years people will be astonished to see how little time must pass to render data carriers unusable because they break or because you don't have the devices anymore," he said. "The second shock will probably be what fraction of the objects we can't use or access in 25 years and that's hard to predict."
Zdroj: Reuters.com
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New genes involved in human eye color identified
Three new genetic loci have been identified with involvement in subtle and quantitative variation of human eye colour. The study, led by Manfred Kayser of the Erasmus University Medical Center Rotterdam, The Netherlands, is published May 6 in the open-access journal PLoS Genetics.
Previous studies on the genetics of human eye colour used broadly-categorized trait information such as 'blue', 'green', and 'brown'; however, variation in eye colour exists in a continuous grading from the lightest blue to the darkest brown. In this genome-wide association study, the eye colour of about 6000 Dutch Europeans from the Rotterdam Study was digitally quantified using high-resolution full-eye photographs. This quantitative approach, which is cost-effective, portable, and time efficient, revealed that human eye colour varies along more dimensions than are represented by the colour categories used previously.
The researchers identified three new loci significantly associated with quantitative eye colour. One of these, the LYST gene, was previously considered a pigmentation gene in mice and cattle, whereas the other two had no previous association with pigmentation.
These three genes, together with previously identified ones, explained over 50% of eye colour variance, representing the highest accuracy achieved so far in genomic prediction of complex and quantitative human traits.
"These findings are also of relevance for future forensic applications", said Kayser, "where appearance prediction from biological material found at crime scenes may provide investigative leads to trace unknown persons".
Zdroj: web
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Childhood deafness gene uncovered
A new genetic fault which may account for some cases of inherited deafness has been revealed by Dutch researchers.
It means that parents with the hereditary condition may be able to predict more accurately the chances of passing it on to their children.
The new find, documented in the American Journal of Human Genetics, could even one day contribute to treatments, say the scientists.
One child in 750 is born with severe hearing loss or profound deafness.
The gene in question, labelled PTPRQ, appears to play a role in the development of the inner ear "hair cell" before the birth of the child.
A genetic fault here means that these cells will not form properly or in sufficient numbers, leading to profound deafness or extremely poor hearing.
This can lead to problems throughout childhood, including behavioural and developmental difficulties, and low academic achievement.
Inheritance
The latest gene was tracked down by scientists at Radboud University Nijmegen Medical Centre who looked closely at the DNA of families prone to the condition, looking for shared genetic traits.
There are now more than 60 known locations in our DNA which can contain faulty genes contributing to this form of deafness, although only half the genes in these locations which actually cause the problem are yet to be identified.
Dr Hannie Kremer, who led the research, said: "Our approach is identifying more genes for congenital deafness.
"This knowledge will help improve treatments for patients, genetic counselling, molecular diagnosis and the development of advanced therapeutic strategies."
Dr Sohaila Rastan, chief scientific officer for the deaf and hard of hearing charity RNID, said: "Knowledge of genes causing deafness tells us more about how our hearing works.
"This research will help develop medicines that are desperately needed to prevent deafness and restore hearing."
There are hopes that gene therapy will one day be able to correct genetic defects linked to this type of deafness.
Zdroj: BBC
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Close call with death leaves its mark on DNA
Some lizards escape predators by "dropping" their tail, but the experience appears to leave its mark. After losing their tail, lizards end up with damaging changes to their DNA.
The parts affected are the telomeres – stretches of DNA that cap the ends of chromosomes. Telomeres naturally shorten as cells divide, and shortened telomeres are associated with the effects of ageing. In humans, shortened telomeres are linked to increased risk of heart disease and dementia .
The changes in the telomeres found in lizards that have experienced a close call adds to the evidence that environmental stress has negative effects by eroding telomere length .
To better understand this, Mats Olsson of the University of Wollongong in New South Wales, Australia, and colleagues measured the telomeres of wild sand lizards, Lacerta agilis . They found that telomere length was affected in animals that had dropped their tails to escape attack – especially in males.
Lizards that had been attacked recently were more likely to have shorter telomeres, and this effect was stronger in larger males than in both smaller males and females.
Larger males live more stressful lives than smaller males: they have more contests for female partners and are attacked by more predators. They also have higher levels of corticosteroids than smaller males. The larger lizards reap the reward for their efforts by having greater reproductive success.
Losing their tails, reduces lizards' future survival chances because the regrown tail is an inferior version of the original: it contains no bones, only cartilage, so can't be dropped again. Losing their tail also prompts a shift in behaviour, as the lizards adopt a less active lifestyle.
"Males 'in the fast lane' would be predicted to become more stressed during the mating season, and that is exactly what we see," says Olsson. Females, on the other hand, naturally live a quieter life, under relatively little pressure from predators compared with males.
"Telomere shortening is a more tangled pattern than previously thought," says Steve Donnellan , a molecular biologist at the South Australian Museum who was not involved in the work. We know the rate of telomere loss varies greatly between individuals, and that stress has a role, but we don't know specific factors, Donnellan says. "Here the researchers have identified the very specific causes of stress, seen in males as opposed to females."
Zdroj: New Scientist
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Maker of cancer test loses right to DNA patent
A US medical diagnostics company on Tuesday promised to appeal a court ruling overturning its right to patent DNA sequences used to protect its genetic test for detecting breast and ovarian cancer.
Experts say the judgment could threaten some companies’ business models to develop new diagnostics for medical treatment.
Peter Meldrum, president and chief executive of Myriad Genetics, said he was “disappointed” at Judge Robert Sweet’s decision this week in a New York federal district court, and said he would “vigorously” defend his case in the federal appeals courts.
The action marks the latest twist in a long-running series of legal battles in the US and elsewhere over the rights of companies to seek intellectual property protection on DNA.
While some specialists argue that patents are important to persuade companies to invest large sums in genetic analysis and to stimulate innovation to improve treatment, many have criticised the tactic, including Francis Collins, the researcher who runs the US National Institutes of Health.
Richard Gold, from the Centre for Intellectual Property Policy at McGill University in Canada, said: “If this decision were to be upheld, it would lead to the invalidation of a large number of gene patents – perhaps most – as well as patents over proteins and even some chemicals.
“Myriad is not the only player here. It is clear that companies such as PGxHealth are following a similar path. In my view, the industry has nobody to blame but themselves. Neither they nor university tech transfer have taken seriously the concern by policymakers.”
The American Civil Liberties Union questioned in court 15 claims on seven patents owned or exclusively licensed to Myriad, although the company said before the appeal that 164 additional claims under these patents were not challenged. It also held that an additional 16 patents went unchallenged.
The European patent office in late 2008 upheld Myriad’s rights over its diagnostic test established in a landmark 2001 patent, and overturned a 2004 judgment revoking its rights to the sequenced BRCA1 gene and an associated test licensed from the University of Utah.
While other diagnostic companies developing tests have since received patents and have licensed the technology to others to ensure their widespread use at low cost, Myriad has always kept tight control, insisting that all samples from patients must be sent to its own laboratories or to those of affiliated parties for testing.
Its policy triggered concerns about privacy and the unauthorised use of patient data, as well as worries about the costs of handing over the testing to Myriad’s laboratories. France has since amended legislation to give it the right to override the patent, while other European countries, including the UK, conduct testing using the techniques identified by the company but refuse to pay royalties.
Zdroj: FT.com
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New DNA technique gives names to the unknown dead
RARE snippets of genetic material locked inside fragments of bone and teeth can help identify people who die at war or sea, even when little remains of their bodies. But often there simply isn't enough DNA to be sure. A new technique, recently used to identify the Titanic's "unknown child", could make it easier for bereaved families to get a positive ID.
To extract DNA, researchers mix ground-up fragments of tooth or bone with a solution containing a chemical called EDTA, which removes calcium from bone. Mike Coble of the US Armed Forces DNA Identification Laboratory in Rockville, Maryland, and his colleages increased the concentration of EDTA and added an enzyme called pro-K, which breaks down the crystallised clumps of protein that lock DNA away in bone (Forensic Science International: Genetics , in press). The net effect, says Coble, was to "liberate" more DNA, increasing the chances of identifying remains.
In the case of the unidentified child who died in the Titanic disaster, the new technique enabled Ryan Parr of Lakehead University in Ontario, Canada, to say that the remains were most probably not those of Eino Panula - as initially thought - but another child, Sidney Goodwin.
However, as with most identifications, Goodwin's relies on DNA from mitochondria, because it is more abundant than DNA from cell nuclei. Nickolas Papadopoulos of the Howard Hughes Medical Institute in Baltimore, Maryland, cautions that excluding someone on the basis of mitochondrial DNA (mtDNA) alone might be a mistake.
In a study published this week, his team shows that mtDNA can vary within different tissues of the same individual. Previously it had been assumed that mtDNA was the same in every cell (Nature , DOI: 10.1038/nature08802 ). "It doesn't mean that you can't use mtDNA, it just means that you have to be careful about who you exclude," says Papadopoulos.
Other evidence, like shoes found with the body, suggests that the child was indeed Goodwin. In future, though, Coble's technique should reduce the reliance on mitochondrial matching, as it will often be possible to extract sufficient amounts of nuclear DNA from badly damaged remains.
"In battlefield remains, often all you end up with is bone and teeth," says Louis Finelli, director of the US Department of Defense DNA Registry. "In most cases we weren't getting anything but mtDNA, but this technique means we can use more of the bone and as a result pull out more DNA."
That should come as welcome news to the thousands of families still waiting to find out about loved ones following conflicts like the Vietnam and second world wars. "For them, the wounds are as fresh as if it had occurred yesterday," says Finelli.
Zdroj: New Scientist
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New gene test may help you pick your diet: report
Can't lose weight on a low-fat diet? Maybe you need to cut carbs instead, and a new genetic test may point the way, maker Interleukin Genetics Inc reported on Wednesday.
The small study of about 140 overweight or obese women showed that those on diets "appropriate" for their genetic makeup lost more weight than those on less appropriate diets, researchers told an American Heart Association meeting.
"The potential of using genetic information to achieve this magnitude of weight loss without pharmaceutical intervention would be important in helping to solve the pervasive problem of excessive weight in our society," Christopher Gardner at Stanford University in California, who worked on the study, said in a statement.
Massachusetts-based Interleukin's $149 test looks for mutations in three genes, known as FABP2, PPARG and ADRB2.
The company says 39 percent of white Americans have the low-fat genotype, 45 percent have the type that responds best to a diet low in processed carbohydrates and an unlucky 16 percent have gene mutations that mean they have to watch both fat and processed carbohydrates.
The researchers randomly assigned around 140 women to one of four diets -- the low-carb Atkins diet, the ultra low-fat Ornish diet, the very low-fat LEARN diet or the more balanced Zone diet.
Interleukin went back and tested about 100 of the women for their DNA by using a cheek swab and then looked to see if the women on the "right" diets lost more weight.
MOST EFFECTIVE MATCHES
Over a year, people on diets appropriate to their genetic makeup, as determined by the test, lost 5.3 percent of body weight. People on mismatched diets lost 2.3 percent, the Stanford researchers told the meeting.
Cholesterol levels improved in line with weight loss, they said.
The company said the test looks for genes that affect metabolism.
"One of the gene variations affects absorption of fats from the intestine," Ken Kornman, chief scientific officer at Interleukin, said in a telephone interview. He said people with that particular mutation absorb more fat from their food and thus should avoid fat if they want to lose weight.
Another of the variations affects insulin response -- the body's production of insulin to metabolize sugar, he said. Simple carbohydrates such as sugar and processed flour stimulate people with that particular gene type to store more of the energy as fat.
Ten percent to 16 percent of people have both mutations, and must watch both carbs and fat, Kornman said.
"What we don't know is if they are on the right diet for their genotype whether it affects satiety or feeling full," he said. He said the company planned broader studies to ask these questions.
Interleukin markets the test under the brand name Inherent Health. It also can test who might best lose weight in response to exercise.
Zdroj: Reuters.com
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Gene test can identify bits of cancer in blood
A personalized blood test can tell whether a patient's cancer has spread or come back, offering a better way to see if treatments are working, U.S. researchers said on Thursday.
Having a test that can detect tumors in the blood could help doctors customize cancer treatments, offering more aggressive therapy to some patients while sparing others from unneeded chemotherapy or radiation.
"We're talking about what could be a management tool for a number of patients," said Dr Bert Vogelstein of Johns Hopkins University in Baltimore and the Howard Hughes Medical Institute, who worked on the study published in the journal Science Translational Medicine.
The gene-based test takes advantage of rapid advances in the technology to sequence whole genomes -- all of a person's genetic code -- once a very costly and time-consuming task.
"This is really personalized medicine. This is not something off the shelf," Vogelstein said in a telephone interview. "This is something that has to be designed for each individual patient."
For the study, the researchers took six sets of normal and cancerous tissue from four colorectal and two breast cancer patients, and mapped out the genetic code in each.
In the cancer samples, the team looked for areas in the genetic code where there were extra DNA copies, or where sections of chromosomes had fused together.
"There are about nine or so rearrangements on average in every sample," Dr Victor Velculescu of Johns Hopkins told reporters at the American Association for the Advancement of Science meeting in San Diego. "They are not present in the normal tissue."
Once the team had identified a genetic signature of the tumor, they looked in patients' blood to see if they could find remnants of DNA that had been shed from the tumor.
They found it in two patients with colorectal cancer.
After these patients had surgery to remove their tumors, levels of the tumors' genetic signature or biomarker, fell, but later returned, suggesting that the cancer remained in the patients' bodies. After a second surgery and a round of chemotherapy, the cancer biomarker levels fell again.
The team thinks the blood tests could be used in cancer patients to detect tumors before they grow big enough to be spotted on imaging machines.
Right now, the test is too costly to be practical.
"It costs right now about $5,000 to do it," Vogelstein said. "There is no question in a couple of years that cost will come down by tenfold at least. Then, a test like this will cost less than an MRI or CT scan," he said.
Velculescu said the test could be available to a broad number of patients in as few as two years.
Meanwhile, the team plans to keep refining the technology and has filed for patents for the blood test.
Zdroj: Reuters.com
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The First and Last Meeting of Everyone With a Fully Sequenced Genome
Nearly every person who has had their entire genome sequenced will gather in a single room near Boston on April 27. It’s the last time this will ever happen.
Within a year, the dozen or so people in this elite group will have been joined by a thousand or more people. Soon after that, hobbyists may be roaming the streets with handheld DNA analyzers, high school athletes may experiment with gene therapy to enhance their performance and pharmacists might check our genetic records before filling prescriptions.
“There was a time that only guys in white labcoats had the credentials and training to operate computers,” said Jason Bobe, co-organizer of the GET conference, where the fully sequenced group will meet. ”Nowadays, we’re all experts to some degree. This is happening in genetics too.”
Bobe hopes to recruit 100,000 people to donate their genetic information to create a public database for medical research.
The next five years will bring massive genetics experiments and breakthroughs in personalized cancer treatment, according to Harvard University geneticist George Church. Doctors will test medications on stem cells derived from their patients to check whether they will work.
The first human genome sequence, finished in 2003, cost an estimated $2.7 billion. Today, the price has dropped below $1,500 for a complete sequence, and it’s on the way to becoming so inexpensive that most everyone will be able to afford it.
But it’s not clear how we will use all of that information. Personalized medicine may be the most important use of DNA analysis, but many industries will be affected by the plummeting costs of gene reading equipment.
“Lets not overlook the ways that genomics will be incorporated into other aspects of our lives,” Bobe said, “like our foods, our households, our backyards, consumer goods, our identities and social interactions.”
The shelves of most big grocery stores are already lined with products that contain genetically modified vegetables. Students have used DNA bar code analysis to identify fake tuna in fancy sushi restaurants. And anyone can sign up for a dating website that matches people based on their genetic traits.
“Genetics know-how will have spread even faster than the rise of computers from obscurity in 1980 to access for everyone today, even in developing nations,” Church said.
Access to the event, however, will be limited. Only two-hundred people can attend, and tickets will cost $999. But anyone will be able to watch video clips of the best discussions for free.
Zdroj: Reuters.com
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Genome study shows what cancers have in common
Genetic abnormalities -- missing DNA or duplicate DNA -- that fuel the growth of one type of cancer may actually be at work in several others, U.S. researchers said on Wednesday.
The finding, based on a large-scale study of the genetic make-up of 26 different types of cancers, suggests cancer has less to do with where in the body it occurs, and more to do with the genetic changes that cause it to grow.
"A lot of the events that cause cancer are common between cancers of different tissue types," said Matthew Meyerson of the Dana-Farber Cancer Institute and the Broad Institute of Harvard and the Massachusetts Institute of Technology in Boston, whose study appears in the journal Nature.
"You have breast cancer, lung cancer, cancer of the kidney -- many of the events that cause these cancers are going to be the same," Meyerson said in a telephone interview.
"What that means for treatment is that many treatments may be used across many different kinds of cancers."
The finding is based on an effort started in 2004 to systematically map the genetic changes across different types of cancers.
The team focused on specific aberrations in the genetic code known as somatic copy-number alterations, in which segments of a tumor's genome contain extra copies of a piece of DNA or lack the segment altogether.
For the study, the team collected more than 2,500 cancer specimens representing more than 24 cancer types, including lung, prostate, breast, ovarian, colon, esophageal, liver, brain and blood cancers.
They combined this with publicly available data from another 600 tumor samples.
"What we're seeing here is that the copy number events that are happening in some of one cancer type are happening in some of another cancer type," Meyerson said.
Out of 17 different types of cancer, they found that most copy number changes -- either extra or missing DNA -- were present in more than one type.
For drug companies, Meyerson said the finding suggests that rather than developing drugs to treat a specific type of cancer, companies may need to focus on drugs that target genetic changes that drive cancer growth.
"In principle, there could be broader drugs that could be effective against many cancers," he said.
Zdroj: Reuters.com
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Gene tests fail to predict women's heart risks
Gene tests that combined over 100 genetic mutations proved ineffective at predicting a woman's risk of a heart attack or stroke, U.S. researchers said on Tuesday.
They said high cholesterol, high blood pressure and a family history of heart disease were the strongest predictors of a woman's heart disease risk.
Many variations of genes have been identified that are associated with a higher risk of heart disease, but combining them into a risk prediction score did not help researchers find which women in a study of 19,000 participants would eventually develop the disease.
They found that after adjusting for traditional heart risk factors, a genetic risk score that combined 101 so-called single nucleotide polymorphisms or SNPs -- a single-letter change in the genetic code -- was not useful in predicting heart disease risk.
For years, teams have been using a tool called a genome-wide association study, in which researchers compare the genomes of people with a disease to those of healthy people, to look for common genetic differences that could help predict disease.
"While multiple genetic markers associated with cardiovascular disease have been identified by genome-wide association studies, their aggregate effect on risk beyond traditional factors is uncertain, particularly among women," Nina Paynter of Brigham and Women's Hospital in Boston, and colleagues wrote in the Journal of the American Medical Association.
The team developed two genetic risk scores based on genetic markers known to be associated with either heart disease or factors that cause heart disease, such as high cholesterol.
During follow-up, women in the study had 199 heart attacks, 203 strokes, 63 deaths from heart disease and 312 procedures to open blocked arteries.
After adjusting for traditional heart disease factors, such as blood pressure and total cholesterol, the genetic risk score was not associated with heart disease risk.
Instead, they found that family history of an early heart attack was one of the biggest independent risk factors.
"Our findings confirm the importance of family history of cardiovascular disease, which integrates shared genetics, shared behaviors, and environmental factors," Paynter and colleagues wrote.
"While the importance of genetic data in understanding biology and etiology is unchallenged, we did not find evidence in this study of more than 19,000 women to incorporate the current body of known genetic markers into formal clinical tools for cardiovascular risk assessment," they wrote.
Zdroj: Reuters.com
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UK scientists say find cheap, fast gene test method
British scientists say they have developed a way of pinpointing variations in a person's genetic code using a chemical test on saliva, meaning quick, cheap DNA tests for risks of certain diseases may be around the corner.
Researchers at Edinburgh University said their technique, based on chemical analysis, can deliver reliable results without the need for expensive enzymes used in conventional DNA testing.
Juan Diaz-Mochon of the university's School of Chemistry, who led the research, said the chemical method was able to detect genes linked to cystic fibrosis in laboratory experiments using synthetic DNA.
With funding from commercial partners and the Scottish Enterprise fund, he said his team planned to market a cystic fibrosis test very soon and then run further research to see if the same method could be used to decode entire human genomes.
"We're hoping to bring the first test for cystic fibrosis to the market within five months," he told Reuters. "With the scientific data we already have, we believe we can develop this test further and in different ways."
Tests which identify tiny variations or omissions in DNA code are increasingly being developed and marketed as ways of determining whether or not a person is healthy, susceptible to disease, or has a disease or serious risks of developing one.
Cystic fibrosis, a life-threatening inherited disease in which internal organs such as the lungs and digestive system become clogged with thick sticky mucus, is one of a small number of diseases caused by a single, identifiable faulty gene.
Companies around the world are racing to develop ever faster and cheaper gene sequencing techniques to offer scientists and drug developers swifter routes mapping whole genomes.
U.S. firm Illumina launched its latest genome sequencing tool, HiSeq 2000, in January and challenges rivals at Life Technologies, Roche, Affymetrix, Agilent Technologies and Helicos BioSciences.
Experts say the "holy grail" for such firms is to be able to decode a person's entire genetic sequence for $1,000.
Diaz-Mochon said the his chemical method would offer a "speedy, cost-efficient alternative" to existing DNA analysis.
"The market for DNA testing is quickly expanding as it becomes more affordable. Our method could help reach the goal of complete genome analysis in a few hours for less than $1,000," he said in a commentary about the study, which was published in the journal Angewandte Chemie and funded by Scottish Enterprise.
Mark Bradley, who also worked on the study, said the team planned to extend their collaborations with researchers and companies working in DNA "and establish our first commercial operations within the next six months."
Zdroj: Reuters.com
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Optogenetics: controlling brain cells with lasers
Brain cells can be switched on and off like light
bulbs using newly identified microbial proteins that are sensitive to
the colour of laser light.
The discovery is the latest in the fast-moving field of optogenetics ,
which has already given researchers unparalleled control over brain
circuits in laboratory animals. The technology may lead to treatments
for conditions such as epilepsy, Parkinson's disease and blindness. New Scientist explains the science and its promise.
How do scientists control brain cells with lasers?
Neurons
fire when electrically charged atoms – ions – flood in and out of them,
creating a tiny electric potential across their membranes. In 2005, a
team at Stanford University in California reported that light-sensitive
microbial proteins that also move ions can cause the same changes when they are genetically engineered into neurons .
One
algal protein, channelrhodopsin-2, turns neurons on when bathed in blue
light, while its foil, halorhodopsin, silences neurons under yellow
light.
If these proteins are already around, what's new?
Channelrhodopsin-2 works swimmingly: it recently helped identify a brain circuit that, when activated, may ease symptoms of Parkinson's .
However,
halorhodopsin has fallen short of hopes. The protein fails to fully
silence neurons and grows sluggish after repeated cycles of light, says
Ed Boyden , a neuroscientist who worked on both proteins at Stanford with his colleague Karl Deisseroth : "It didn't work very well and it hasn't found much of an application."
Now,
Boyden's team at the Massachusetts Institute of Technology has
discovered two new light-sensitive proteins that are up to the task, at
last offering an on/off switch for brain cells. "We can do digital
shutdown of neurons," he says.
Why is that useful?
For
one, the new proteins give researchers the power to tease out how
specific brain circuits underlie behaviour, Boyden says. They can be
genetically engineered into specific kinds of neuron, such those
involved in forming certain kinds of memories. These cells could then
be turned off in laboratory animals to see how their behaviour changes.
Furthermore,
one of the newly discovered proteins, called Mac, shuts off neurons
under blue light instead of yellow. By expressing Mac in one cell type
and a yellow-sensitive "off switch" protein in another, it would be
possible to independently silence two sets of neurons that originate in
a single area, such as the prefrontal cortex, but dart off to different
parts of the brain.
Will optogenetics ever be used to treat diseases in humans?
It's
hard to say. However, clinical trials may begin in the next decade,
says Boyden, who is involved in a company, Eos, that aims to use
optogenetics to treat blindness. Another fledgling firm is hoping to apply the technology to spinal cord injuries .
The
success of these efforts will depend on the ability to safely and
effectively send genes and light to neurons – no easy feat.
Even if human brains never come under the control of lasers – as those of flies , mice and even monkeys now have – optogenetics will almost certainly lead to medical breakthroughs, Boyden contends.
If
optogenetic research can establish the brain circuits disturbed in
neurological and psychiatric illnesses, these cells could be targeted
with drugs or more established technologies such as deep brain stimulation . "We can use these tools for real principles of treatment," he says.
Zdroj: New Scientist
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'Junk' DNA linked to aggressive cancers
Rogue genetic elements previously dismissed as "junk" DNA may play a role in the development of some cancers , or at least act as a marker of the disease's progression.
That's
the conclusion of a study that found that some recurrent DNA sequences
previously thought to be nothing more than molecular parasites appear
to be active, but only in breast and colon cancer cells.
"If
this 'junk' DNA does turn out to play a role in cancer then we could be
at the tip of the iceberg in understanding a completely new mechanism
behind the disease," says Cristina Tufarelli at the University of
Nottingham in the UK.
Hidden function
Only
about 3 per cent of the human genome actually encodes instructions into
RNA for making proteins. Much of the rest has no apparent role and is
often dismissed as junk . Sometimes, however, what seems like junk later turns out to have a function after all.
About
17 per cent of our DNA is made up of recurrent sequences called L1
elements that have colonised the genome by making copies of themselves
and inserting these into new locations. Many geneticists had dismissed
L1 elements as molecular parasites that do nothing but further their
own survival, but recent studies have hinted that they are sometimes
transcribed into RNA too.
To
investigate if there might be differences in the transcription of L1
elements in cancerous cells, Tufarelli and her colleagues compared RNA
transcripts in human breast cancer cell lines with those found in
normal breast cells.
They
found two L1 RNA transcripts that were present in both cell lines and
five that were present only in the breast cancer cells.
Invasion implication
A
similar analysis on colon cancer cell lines and normal colon cells also
revealed some L1 elements that were only transcribed in the cancerous
cells.
What's
more, three of the L1 RNA transcripts found in the colon cancer cells
were only found in the most aggressive cancers, suggesting that they
may be linked to the progression to a more invasive type of tumour.
Since
L1 elements have previously been found on DNA next to or even within
some tumour-suppressor genes, Tufarelli suggests that they might
influence the progression of cancer by reducing, or down-regulating,
the expression of these genes.
Driver or by-product?
The
next step is to confirm whether L1 elements are driving cancer, or
whether the L1 transcripts found in tumours are simply the result of
the cancer itself.
If
they are driving it, drugs could be developed that target specific L1
elements, potentially slowing cancer progression. Even if they are
innocent by-products, they might be useful in diagnosing or monitoring
the disease.
"We
are learning more about the genes involved in cancer but these
so-called 'junk' regions receive relatively little attention," says
Lesley Walker, director of cancer information at Cancer Research UK,
which funded the research. "We are beginning to see that they could
play a really important role."
Zdroj: New Scientist
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Unreliable evidence? Time to open up DNA databases
WHEN a defendant's DNA appears to match DNA found at a crime scene, the probability that this is an unfortunate coincidence can be central to whether the suspect is found guilty. The assumptions used to calculate the likelihood of such a fluke - the "random match probability" - are now being questioned by a group of 41 scientists and lawyers based in the US and the UK. These assumptions have never been independently verified on a large sample of DNA profiles, says the group. What's more, whether some RMPs are truly as vanishingly small as assumed has been called into question by recent insights into DNA databases in the US and Australia. The group, led by Dan Krane of Wright State University in Dayton, Ohio, is demanding access to CODIS - the US national DNA database, which contains over 7 million profiles - so that they can test the assumptions behind RMPs. They have outlined their arguments in a letter, which was published in Science in December (vol 326, p 5960). "The national US database is a truly enormous source of data," says signatory Larry Mueller of the University of California, Irvine (UCI). Such research could reveal if incorrect RMPs are prompting jurors and judges to attach undue weight to DNA evidence, possibly leading to miscarriages of justice. Even if these fears are not borne out, independent checks on the DNA held in large databases like CODIS are vital to maintaining confidence in DNA evidence presented in courts all over the world, the group says. Access would also allow the number of errors in CODIS to be measured. DNA evidence, considered the gold standard in forensic science, is typically used in two ways: to link a known suspect to a crime, or to find new suspects - known as a "cold hit" - by searching for a match in a DNA database of known criminals. Before a match can be sought, a profile is generated from a DNA sample by analysing specific locations on the chromosomes, called loci, and looking at short sections of non-coding DNA, known as short tandem repeats (STRs), which vary between individuals. An RMP is then arrived at using the estimated frequencies of these STRs, or alleles, at all the loci investigated. The more loci that are analysed at once, the more comprehensive the profile and the smaller the RMP. Labs in the US typically look at 13 loci, while UK labs tend to look at 10. One thing that researchers would like to use CODIS to verify is whether the allele frequency estimates are correct. Most of these estimates are based on data from small studies conducted during the early years of DNA forensics. But there are signs that these studies did not capture the true frequencies of certain alleles in some populations, which could mean that the RMPs presented in court are wrong. "When you look at real offender databases you see that there are shocking differences between what you actually see and what you would expect to see," says Krane. Offender databases reveal shocking differences between what you see and what you would expect The first clue that something might be amiss came in 2005, when limited data was released from the Arizona state database, a small part of CODIS. An analyst who compared every profile with every other profile in the database found that, of 65,493 profiles, 122 pairs of profiles matched at nine out of 13 loci and 20 pairs matched at 10 loci, while one pair matched at 11 loci and one more pair matched at 12 loci. "It surprised a lot of people," says signatory Bill Thompson of UCI. "It had been common for experts to testify that a nine-locus match is tantamount to a unique identification." Unexpected matches Similar tests have since been conducted on the Illinois state database (of 220,000 profiles, 903 pairs matched at nine or more loci) and the Maryland state database (of the 30,000 profiles, 32 pairs matched at nine loci, and three matched on all 13 loci). One possibility is that some are duplications of the same profile in the databases - although this is not the case with the Arizona matches. Alternatively, assumptions about the frequency of alleles in populations, such as how independent these variations are of each other, might be wrong. If this is the case, access to the database is vital if these assumptions are to be corrected. "We need to learn how DNA profiles cluster by race, ethnicity and even geography," says Krane. We need to learn how DNA profiles cluster by race, ethnicity and even geography A third possibility is that the surprisingly high number of matches found in these databases is the result of large numbers of relatives in the database, who are more likely to have similar DNA profiles than non-relatives. This could mean that in areas of the US and other parts of the world with more closely related populations, the RMPS may need to be tweaked. So if CODIS provided new knowledge of the frequency of certain alleles in related or unrelated people, what would the subsequent adjustments of RMPs lead to? Even with such tweaks, in cases where all 13 loci are matched, the chances of it being a coincidence will still be vanishingly small. But a 13-loci match is not always possible. If only small amounts of DNA are recovered from crime scenes, or if samples are degraded or mixed with other people's DNA, the number of loci available for comparison is often much lower than 13. This means that the statistical weight attached to a match is lower - and the probability of a coincidental match higher. "I would say 5 to 10 per cent of database searches involve evidence profiles with fewer than 10 loci and/or that are mixtures," says Mueller. For such cases, RMPs will be much higher, so tweaks to these estimates could make a big difference to how a jury interprets them. "I've been involved in cases where these are 1-in-67 or 1-in-83," says signatory Bill Shields of the State University of New York at Syracuse. "If those numbers are off by 50 per cent, then that could make a big difference to a jury." Bruce Budowle, former senior scientist at the FBI, which controls CODIS, argues that fears sparked by the Arizona database are overblown. Selecting a known suspect's profile and comparing it against a crime scene profile is a bit like taking a person whose birthday is 9 January and calculating the chance that a specific other person shares that birthday, which is about 1 in 365. The comparisons made within the Arizona database were the equivalent of asking how many people in a room share any birthday - a different statistic altogether. With just 23 people, for example, the probability that any two share any birthday exceeds 50 per cent. With 60 people, it is nearly 100 per cent. The signatories insist that this "birthday problem" can't explain all the matches, however. In 2008, Mueller developed a computer model of the Arizona database that showed that the birthday problem could account for a few, but not all of the matches (Journal of Genetics, vol 87, p 101). Access to DNA databases is not just about preventing potential miscarriages of justice. In 2003, when Krane was given limited access to the DNA database for the Australian state of Victoria as part of the inquest into the death of a toddler, he noticed a cluster of 32 profiles that seemed to match at 17 of the 18 alleles tested for. This was odd because far fewer matched at just 16 alleles - you would expect the opposite to be the case. Krane says the most likely cause is mistakes made when the samples were entered into the database, which he estimates may be present in as many as 1 in 1000 samples. Access to CODIS would reveal if it contains errors, too, which could be causing investigators searching for a cold hit to miss potential suspects. "If you have mistyped an allele or a locus, then you have a person in a database whose profile would not match his own DNA," says signatory Bicka Barlow at the San Francisco Public Defender's Office. Will the FBI grant scientists access to CODIS? Director of the FBI Laboratory, Christian Hassell, says he appreciates the concerns the Science letter raises. "We are exploring ways to investigate some of the topics," he adds. But he has turned down the request for access, citing concerns about genetic privacy. The letter's signatories point out that medical researchers who work with DNA overcome privacy issues regularly, for example by signing an agreement promising not to divulge the data and taking certain security measures. Without external scrutiny of the databases, doubts will remain, Mueller argues. "All of this... can be resolved by letting scientists have access to the data to do what they need to do."
Zdroj: New Scientist
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Genetic breakthrough hails new cancer research era
The genetic code of two of the most deadly cancers has been cracked by British scientists in a world first that opens up a whole new era in the treatment for the disease. All the mutations that turn healthy cells cancerous in both lung and skin tumours have been identified in what researchers described as a "transforming moment" in the search for preventions, treatments and cures for both terminal illnesses. Such a detailed picture of the fundamental causes of the disease will lead to earlier detection, new breeds of drugs and better understanding of what causes the disease, they claim. Eventually a simple blood test will lead to accurate "made to measure" treatments that can identify, attack and kill the causes of each patient's own individual cancer, they claim. Professor Mike Stratton, of the Wellcome Trust Sanger Institute, a world leading research centre in Cambridge who carried the studies, said: "What you are seeing today is going to transform the way that we see cancer. "This is a really fundamental moment in the history of cancer research." All cancers are caused by damage or mutations to the DNA of formerly healthy cells acquired during a person’s lifetime. This damage causes them to grow into abnormal lumps or tumours and spread around the body disrupting its normal processes and eventually – if unchecked – causing death. In lung cancer the damage is almost entirely caused by smoking and in skin cancer or malignant melanoma by ultra violent sunlight. The Sanger Institute studies used powerful new DNA sequencing technologies to decode completely the genome of both tumour tissue and normal tissue from a lung cancer and a malignant melanoma patient. They then compared and contrasted the two to discover the differences and see what damage has occurred to cause the disease. The lung cancer genome, which kills 34,500 people a year, contained more than 23,000 mutations, the melanoma, which kills 2,000 people a year, more than 33,000. Most of these mutations are known as "passengers" and cause damage but not cancer. However a small number are called "drivers" and these lead to the disease. By sequencing many more cancer patients over the next few years, the researchers hope to distil down the mix until they have a handful of targets to hit with treatments such as chemotherapy and radiotherapy. While the whole process for the studies took more than a year and cost around £80,000, the technology is moving so fast that it will soon take just weeks and cost less than £8,000 – well within the current cost and time frame for cancer treatments. It is eventually believed that a simple blood test will mean every patient will be given their own cancer chart so their treatment can be tailor made. "The first time that people began to think there was something about genetic material that contributed to cancer was about 100 years ago and they looked down the microscope at the nucleus (centre of cells) and saw it was abnormal," said Professor Stratton. "100 years later, today, we are seeing every single mutation in a cancer. We have never seen cancer revealed in this form before and these catalogues of mutations are telling us about how the cancer has developed so they will inform us on prevention. "And they include all the drivers which tell us about all the processes that are disrupted in the cancer cell and which we can try and influence through our treatments." Already the lung cancer genome is yielding useful information. As the average victim has smoked 18,000 packets of cigarettes, the researchers have concluded that a mutation is caused roughly every 15 cigarettes. Professor Peter Campbell, who led the lung cancer team, said: "These mutations are a bit like Russian roulette. Most of the time you will hit an empty chamber and cause a passenger mutation. "But every now and again you will hit a bullet and cause a tumour." The research, published in the journal Nature, was hailed as groundbreaking by fellow researchers. Professor Carlos Caldas, a cancer expert from Cancer Research UK’s Cambridge Research Institute, said: "This is groundbreaking research. "Like molecular archaeologists, these researchers have dug through layers of genetic information to uncover the history of these patients' disease. "By repeating and refining this technique with other forms of cancer, and comparing the results to data from the Human Genome Project, the hope and excitement for the future is that we'll eventually have a detailed picture of how different cancers develop, and ultimately how better to treat and prevent them." Dr Elizabeth Rapley, of The Institute of Cancer Research, added: “These are exciting studies that show us a great deal about how cancer is triggered and driven by mutations in DNA. "This is the first time that a complete cancer genome has been sequenced and similar insights into other cancer genomes are likely to follow. "As more cancer genomes are revealed by this technique, we will gain a greater understanding of how cancer is caused and develops, improving our ability to prevent, treat and cure cancer.” Harpal Kumar, Cancer Research UK’s chief executive, added:“This fascinating work shows that great progress is being made to understand a lot more about how cancer develops. “Cancer Research UK is extremely encouraged by this fast-emerging area of research. Never before has the potential of genomics to bring benefits to patients been so apparent, and we are already planning major new investments to add further depth to this cutting-edge work."
Zdroj: Telegraph
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Know a gene's 'parent' to improve disease prediction
PONDERING whether a baby got mum or dad's eyes may seem like idle speculation, but knowing which parent certain genes came from can tell you about your risk of disease. Some variants are even two-faced, boosting the risk if they come from one parent but cutting it if they come from the other. It is already known that the same gene variant can behave differently depending on which parent it came from, due to a process called imprinting - which determines which of a parent's genes are expressed in the child. Now a team led by Kári Stefánsson at deCODE genetics in Reykjavik, Iceland, has looked at hundreds of thousands of single-letter DNA variations to examine how imprinting affects the risk of disease. For 38,000 Icelanders, his team determined whether these variations came from the mother or father, and looked for correlations with disease. The researchers identified at least five variations whose correlation with a certain disease depended on whether the gene is maternal or paternal. An earlier study that didn't take parental influence into account found one variant on chromosome 11 raised the risk of breast cancer by 7 per cent. Stefánsson's study shows that it in fact ups the risk by 17 per cent if inherited from the father but protects against the disease if it comes from the mother. The team also found disease-linked variants that other studies had missed. One of these boosts a person's risk of type 2 diabetes by 41 per cent, but only if they inherit it from the father. Mental illness "We are going to find more common variants underlying disease, and this is one example of that," Stefánsson says. By uncovering these hidden variations, researchers should be able to better explain the hard-to-find genetic components of diseases such as mental illnesses, says Randy Jirtle, an epigeneticist at Duke University in Durham, North Carolina. "This paper brings to the forefront the real importance of genomic imprinting in disease susceptibility, which we miss a lot of the time," he says.
Zdroj: New Scientist
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DNA's guardian gene found in placozoans
A vital gene that defends us against cancer has been found in one of the simplest of animals – a flat, amoeba-like creature called a placozoan. The discovery shows that p53, sometimes described as the "guardian of the genome", has been around for over 1 billion years. The Placozoa are among the most primitive of animals. Their millimetre-long bodies are just three cells thick and have no muscles, nervous systems or organs. They even lack an obvious front or back end. Yet placozoans have a version of p53, also known as TP53, that is strikingly similar to ours, says David Lane, chief scientist at Cancer Research UK. Lane first discovered p53 in 1984. In humans, the protein it codes for, p53, detects damaged DNA that could trigger cancers. It stops the growth of cells containing damaged DNA by encouraging them to self destruct or by recruiting other proteins to repair the damage. Cancer signature Faulty or inactive copies of the gene greatly increase the chances that a cell will become cancerous, and more than half of all tumours lack working copies of it. It is not clear whether p53 has the same function in placozoans. Previous research suggests that the gene originally controlled stem cells or immune response and was only co-opted to defend animals against rogue cells once they became large and long-lived enough to need it. "Tumour suppression could be a rather recent 'recycling' of p53 functions that were initially evolved to do something else," says Karen Vousden from The Beatson Institute for Cancer Research in Glasgow, UK. Nonetheless, human and placozoan versions of p53 share essential features, including regions that allow it to attach to DNA and other proteins. These conserved areas suggest it has interacted with a similar network of partner genes since the dawn of the animal kingdom. Gene partners One such partner is Mdm2. In humans, it keeps p53 in check, controlling when the protein is released. Lane has found that placozoans have a version of Mdm2 that does the same thing. Vousden, who discovered the relationship between the two genes, was surprised that Mdm2 exists in such simple animals. "We had believed that Mdm2 was quite recent in terms of evolution," she says. The results, due to be published in February in the journal Cell Cycle, also shed light on the puzzling evolutionary history of p53 in other animals. Surprisingly, human p53 is a closer match to the placozoan version than it is to counterparts in more closely related animals such as flies and worms. Lane thinks this is because the ancestor of flies and worms duplicated its copy of p53; the original version was lost and it is the divergent copy that now defends their DNA. The discovery was only possible because the entire placozoan genome was recently sequenced, work which provides clues about genes that were important to the success of the earliest animals.
Zdroj: New Scientist
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The DNA snatchers: Police arresting innocents just to grab genetic details for Big Brother database
Police are arresting innocent people in order to get their hands on as many DNA samples as possible, senior Government advisers revealed last night. The Human Genetics Commission said the Big Brother tactic was creating a 'spiral of suspicion' among the public. The panel - which contains some of Britain's leading scientists and academics - said officers should no longer routinely take samples at the point of arresting a suspect. They also called for all police - including support staff - to place their own DNA on the national database in a show of solidarity with a public being routinely placed under suspicion. By law, officers are only allowed to make an arrest if they have ' reasonable suspicion' that a person has committed a crime. But the HGC, which has carried out a lengthy review of the merits of the database, said evidence had emerged of police arresting people purely so they could take their DNA. Its chairman, Professor Jonathan Montgomery, said: 'People are arrested in order to retain DNA information that might not have been arrested in other circumstances.' The claim, which was backed by evidence from a senior police officer, delivers a significant blow to the Government's defence of the database - which contains more than 5.6million samples. Campaigners have long feared officers were carrying out mass sweeps of the population to load their samples on the database, and make future crime fighting easier. The result is one million entirely innocent people having their genetic details logged by the state. The Commission said one of the consequences of current DNA laws was that young black men are 'very highly over-represented', with more than three quarters of those aged 18-35 on the database. Professor Montgomery warned this was creating a 'spiral of suspicion' among sections of society. A retired senior police officer, a superintendent, told the commission: 'It is now the norm to arrest offenders for everything if there is a power to do so. 'It is apparently understood by serving police officers that one of the reasons, if not the reason, for the change in practice is so that the DNA of the offender can be obtained.' Officers in England and Wales are entitled to take samples from everyone they arrest for a recordable offence. Proposals within the Crime and Security Bill - published last week - will for the first time put a time limit, in most cases six years, on how long profiles are stored when the alleged offender is either not charged or later cleared. But there are no plans to reduce police powers to take samples on arrest. One possibility is to only take DNA when a suspect is charged - making it harder for police to target innocents for their DNA. In a 110-page report, the commission said more detailed research is required to evaluate how useful the database is in helping to solve crimes, describing current evidence as 'flimsy'. It accused politicians of using single case studies where the database has secured a conviction instead of carrying out a rigorous evaluation of its scale and function. Latest Government figures show the costs of running the system - the largest in the world - have risen dramatically, to £4.3million from £2.1million in just a year. Over the past two years, more than 1.17million new profiles have been added to the database but the number of DNA-related detections fell from a peak of 41,148 in 2006-07 to 31,915 in 2008-09. LibDem spokesman Chris Huhne said: 'The Government's cavalier attitude to DNA retention has put us in the ridiculous situation where people are being arrested just to have their DNA harvested. 'Ministers make no distinction between innocence and guilt and as a result everyone is treated like a suspect.' Liberty warned police were being given a 'perverse incentive' to arrest individuals just to get their details on the database. Tory home affairs spokesman James Brokenshire said: 'For too long the Government has had a policy of growing the DNA database for the sake of it, regardless of guilt or innocence.' Tories last night attacked reported Government plans to charge innocent people a £200 fee to apply to have their names removed from the national DNA database. And they called for England and Wales to follow the Scottish model by not retaining the DNA of such innocents, save in exceptional circumstances. The Government has proposed such DNA should be kept for six years. Tory security spokesman Baroness Neville-Jones told the Lords: 'If it is the case that making an application for removal is subject to a £200 fee, several individuals will be prevented from making any appeal or indeed getting their names off the database. 'Perhaps the Government is using the right of individuals to appeal to help fill the big public sector deficit.'
Zdroj: web
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Fairfax snares center for genetic research
A $200 million genetic research facility planned for Fairfax County
could bring with it thousands of jobs over the next decade and spur
spinoff businesses that would focus on the fast-growing field of
personalized medicine, Virginia officials and researchers said Monday
as they announced the move.
Enticed by millions of dollars in tax breaks and a location close to
universities and federal agencies, officials with the Ignite Institute
for Individualized Health, a nonprofit organization specializing in DNA
research, announced that the center's facility would be in a
300,000-square-foot campus in the Northern Virginia suburb. A location
has not been selected.
The institute's founder, California geneticist Dietrich Stephan,
said the institute would create 415 jobs in the region over the next
five years and would partner with Fairfax-based Inova Health System,
the community hospital company where Stephan will serve as an executive
director.
"This is the place where personalized medicine will take root and flourish," Stephan said.
Virginia Gov. Timothy M. Kaine (D) was on hand for Monday's
announcement, along with Gov.-elect Robert F. McDonnell (R). Kaine
called the Ignite center "not just a catalyst but an accelerator of
biotechnical expertise in Virginia."
San Francisco and Boston were also considered as potential sites for
the lab, but Stephan said the Washington area was a "perfect fit," with
its educated workforce and proximity to the nation's capital.
Research at the Ignite Institute will focus on personalized medicine
using patients' molecular blueprints -- a rapidly developing industry
in which therapies can be "made to order" for diseases such as
Alzheimer's, autism, cancer and diabetes. Drugs can be chosen based on
their interaction with specific genes, and gene analysis, or
genotyping, can screen for congenital conditions years before symptoms
crop up. At Ignite, doctors and researchers will work side by side in
an attempt to create drugs and medical devices, said J. Knox Singleton,
Inova's president and chief executive.
Ignite will differ from similar facilities in that it will focus
more on the practical applications of its DNA research, said Timothy A.
McCaffrey, professor and vice chairman of the Department of
Biochemistry and Molecular Biology at George Washington University's
School of Medicine and Health Sciences.
"While this DNA research has matured, many doctors have been slow to
integrate it," McCaffrey said. "You have to remember, there's a lot of
physicians out there that were trained when Watson and Crick first
discovered the DNA sequence in the 1950s. So to actually incorporate
this technology with patients, to me, is a game-changer."
Fairfax beat out neighboring Loudoun County
in snagging the facility; Loudoun had been pursuing the project but
didn't offer the financial advantages Fairfax proposed, officials said.
Fairfax County Board of Supervisors Chairman Sharon Bulova (D)
touted the move as a sign the county had become a "major player" in the
national biotechnology industry. She also said the institute would
provide a boost to the county's commercial tax base, as did moves by
Hilton Hotels and Science Applications International Corp. to Fairfax
this year.
Zdroj: washingtonpost.com
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DNA database
Emma Riccobena presents something of an under-informed, alarmist take on issues surrounding the UK's National DNA Database (3 October, p 29) . As one of the "experts" to whom she refers, I would be delighted to respond.
Riccobena's
contention that a DNA database would lead to corrupt experts framing
celebrities for money applies to any other evidence type, including
eyewitness testimony and CCTV, and disregards the excellent work done
by scientific experts - working for the defence, in many cases - who
enforce the rigorous application of science.
One
way to prevent the planting of genetic material that has been stolen
from a DNA database is a comprehensive national database in which only
the profile - not the genetic material itself - is stored. The use of
new, more advanced profiling tests can future-proof such a database,
eliminating the need for tissue retention for future re-sampling. Such
profiles do not include information specific to race, appearance or any
genetic conditions that could be abused by any hypothetical, future,
dystopian government, eliminating many of the privacy concerns such
proposals often attract.
Lastly,
the trustworthiness of forensic experts of all kinds is one of the hot
topics in the UK forensic science community. The Forensic Science
Society works to ensure that people giving evidence in our courts are
qualified and competent to do so.
Zdroj: New Scientist
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Boys with ALD bring gene therapy in from cold
Gene therapy is coming in from the cold. Two boys treated three years ago with a gene therapy for X-linked ALD , the brain disease featured in the film Lorenzo's Oil , fared so well that doctors have treated a third and are now looking for adult volunteers.
"They have normal, family lives," says Nathalie Cartier
of the Descartes University in Paris, France, a member of the team that
pioneered the ALD gene therapy. "We want to treat more children in
France and the US, and adults with the disease."
ALD
is caused by a faulty gene that prompts the myelin sheath coating
nerves in the brain to wear away, causing impaired speech, movement and
eventually death.
Defective gene
Cartier
and her colleagues took blood stem cells from two 7-year-old boys with
ALD, infected the cells with a virus carrying a correct copy of the
defective gene, then re-injected the stem cells. The boys' symptoms
stabilised within 14 months and have not worsened since.
Early gene therapy trials were stopped after triggering cancer . Previously, the only treatment for ALD was an oil developed by the parents of Lorenzo Odone who died in 2008 aged 30 .
Journal Reference: Science , DOI: 10.1126/science.1171242
Zdroj: New Scientist
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Evidence recovered from dirty DNA samples
CONTAMINATED crime-scene DNA samples that would
normally be written off as forensically useless can now be rescued,
thanks to amplification enzymes that tolerate pollution.
Before
a profile can be obtained from a DNA sample recovered from a crime
scene, it must be amplified using enzymes called polymerases.
Pollutants such as tobacco or aluminium from drink cans can stop the
enzyme working, but now Johannes Hedman and colleagues at the Swedish National Laboratory of Forensic Science have come up with some alternatives to the AmpliTaqGold enzyme, which is preferred by forensic labs.
The
team amplified 32 polluted samples of saliva using three other
polymerases regularly used to process non-forensic samples. Of these
samples, 20 showed statistically significant improvements in the
quality of the profile compared with using AmpliTaqGold (Biotechniques , vol 47, p 351).
Hedman suggests that employing these enzymes could be useful for samples that till now would not yield a complete DNA profile.
Zdroj: New Scientist
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Nanoparticle DNA damage study: what you should know
Nanoparticles can damage the DNA of cells some
distance away, even when the cells seem safe behind an impassable
barrier of tissue, new research has found.
But what does this curious finding ,
revealed yesterday by researchers at the University of Bristol, UK,
mean about the safety of nanoparticles and medical treatments based on
them? New Scientist puts the news in context.
Did the experiment represent something that could happen in my body?
The
experimental set-up was entirely artificial, and nothing like it occurs
naturally in humans or animals. Nor are the nanoparticles in question
used in any current treatments, experimental or otherwise.
The
tissue barrier, about four cells deep, was made from "BeWo" human
cancer cells. They are a standard cell line that has become well
adapted to lab work, making them very different to any cells found in
the body.
The
nanoparticles were 30-nanometre-wide beads of surgical cobalt-chromium
alloy, a material used in much larger pieces to make surgical implants
such as hip prostheses.
The
"target" cells on the other side of the BeWo barrier to the
nanoparticles were human fibroblast cells, found in skin and connective
tissue.
What exactly were the results?
After
a day in a lab dish, DNA damage was discovered in the fibroblasts. It
wasn't extensive, but included single and double-strand breaks in DNA,
and abnormal chromosome doubling in some cells. Careful checking found
no leaks in the barrier, and no cobalt-chromium beads on the wrong side
of it.
How could that happen?
The
nanoparticles directly influenced the nearest layer of barrier cells
and disrupted their mitochondria – chambers where energy is generated
and stored.
That
released signalling molecules – mainly the energy-transport molecule
adenosine triphosphate (ATP) – which in turn triggered a cascade of
biochemical messages inside the cell. That signalling storm eventually
reached the other side of the barrier cell, opening channels that
spread the message to the next layer of barrier cells.
This
Chinese-whispers process continued until signalling molecules reached
the fibroblasts, somehow damaging their DNA – the researchers don't yet
know how this happened.
How do we know that's what happened?
When compounds that block the "message" channels in cell membranes were added to the dish, there was no damage to fibroblasts.
What is special about these nanoparticles that lets them do this?
Nothing, really. Further experiments showed that there are ways to transmit the ghostly messages without using nanoparticles.
Solutions
containing cobalt or chromium ions caused the same damage to
fibroblasts. So did using much larger particles of cobalt-chromium in
place of the nanoparticles.
Might other kinds of chemicals, drugs and nanoparticles perform this trick too?
Possibly, but the only way of finding out is to test a wider range of substances using the same experimental set-up.
Hundreds
of thousands of people receive cobalt-chromium implants every year, and
there has been no evidence of ill effects reported.
Could the same effect occur naturally?
Possibly,
but we don't know yet. "Maybe small particles like viruses or prions
act through these processes too," says Patrick Case, who led the
research.
Does this suggest that all nanoparticles may be unsafe?
No.
There are hundreds of nanostructures under development and being tested
as possible medical treatments and for other uses. It would be
ridiculous to suppose that they would or could all cause this
phenomenon.
What about skin creams like sunblocks that contain nanoparticles? Might they cause unknown effects below the skin?
Possibly.
But again, this is such a newly discovered phenomenon that it's too
soon to say. The researchers are adamant that their set-up can't and
shouldn't be extrapolated to any structures in the human body.
Is more research into the new phenomenon planned?
Yes. Experiments are planned to see if other nanoparticles or chemicals can perform the same trick.
It
will also be fascinating to see if signalling is possible across the
body's natural barriers, such as the skin, placenta or blood brain
barrier.
Much
research is trying to design drug molecules able to cross such
barriers, which can act as very specific filters. But it may be
possible to exploit this newly discovered effect to avoid having to
cross them altogether.
Zdroj: New Scientist
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Blame It on Your Debt Gene?
When you apply for a mortgage in 10 years, you may be asked for your bank statements, your pay stubs… and a cheek swab. At least that’s one possible implication of a new study, which reports a groundbreaking finding: that whether you carry a specific gene variant can predict your propensity to rack up credit-card debt. Specifically, Jan-Emmanuel De Neve, of the London School of Economics, and James Fowler, of the University of California, San Diego, have found that if you carry one or both “low efficiency” alleles of the MAOA gene — we’ll get to what exactly the MAOA gene is and does in a minute — the likelihood that you have credit card debt increases by 8% and 16%, respectively. It’s a first-of-its-kind result, but what exactly does it mean? Does it mean that humans carry a “debt gene”? And if you were to carry such a gene, does that mean you’re doomed to a life of financial turbulence and tribulation? To begin to answer these questions, one must understand the complex relationship between genes and behavior. Unlike with physical characteristics (such as eye color), behavioral traits (such as violence or impulsivity) are tricky to identify and arise from a tremendously complex interplay of brain systems and environment. The heritability of human behavior has been studied systematically since the 19th century. Traditionally, it’s been studied using twins and adoptees, to tell us how much of a trait is explainable purely by genetics, as opposed to environmental or other influences. And that approach has been extremely fruitful. Recent twin studies, for instance, have shown us that some surprising things have major genetic components: risk-taking, the tendency to cooperate, happiness levels, political preferences — even whether or not a person is likely to turn out to vote, donate to a political candidate, or run for office him or herself. The rising availability of DNA analyses, however, is now making it possible for scientists to try to link specific genes to specific behaviors. So, is there a “debt gene”? “There will never, ever be such a thing as a ‘debt gene’,” says De Neve. But what humans likely have is “a set of genes whose expression, in combination with environmental factors, influences financial decision-making.” The MAOA gene appears to be one of these genes.
Zdroj: web
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Company sequences whole human genome for $1,700
WASHINGTON - Want to know your entire DNA sequence? A California company has done it for as little as $1,700.
Privately held Complete Genomics says it can do a better quality,
usable genome map for about $4,400 -- compared with the $100 million
the Human Genome Project spent to complete the first sequencing of the
human genome in 2000.
"Whole-genome sequencing costs have dropped from the more than $100
million cost of the first human genomes to the point where individual
labs have generated genome sequences in a matter of months for material
costs of as low as $48,000," the company's Radoje Drmanac and
colleagues reported in the journal Science.
"This high-quality, cost-effective approach to genome sequencing
will allow researchers to study complete genomes from hundreds of
patients with a disease to advance the understanding of the genetic
causes of that disease, with an end to preventing and treating common
human ailments," said Cliff Reid, chief executive officer of Complete
Genomics.
Two of the people whose DNA was mapped had taken part in an
international sequencing project called the International HapMap
project -- a man of European descent and a Yoruban female.
The third came from a white man taking part in the Personal Genome
Project, an online registry in which people are asked to donate both
their DNA and a little money.
Genome sequencing is still early stage science. While researchers
can get the code, figuring out what it means is a different matter.
Genomics pioneer Craig Venter had his own genome sequenced -- at a
cost of "several million" dollars -- and found the analysis could only
show he was likely to have blue eyes, for instance. Venter does have
blue eyes.
Last month Pauline Ng of the J. Craig Venter Institute in San Diego
and Sarah Murray of Scripps Translational Science Institute in La
Jolla, California, tested kits provided by California-based firms
Navigenics Inc, a private company, and 23andMe, backed by Google Inc.
They found they varied in predicting disease risk.
Complete Genomics and The Institute for Systems Biology said earlier
this week they plan to sequence the genomes of 100 people to try and
find insights into Huntington's disease.
Scientists also use a technique called genome-wide association to
try to find genes that no one suspected were involved in various
diseases.
Zdroj: Reuters.com
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A new dimension for genome studies
By revealing the 3-D structure of DNA, scientists explain how it manages to stay untangled. The findings could also help reveal how cells regulate their genes. Scientists have long known that DNA is arranged in a double helix. But
if the double helix did not fold further, each cell's genome would be
two meters long — far too large to fit into the nucleus of a human
cell, which is about a hundredth of a millimeter in diameter. A
new paper from scientists at MIT, the Broad Institute of Harvard and
MIT, University of Massachusetts Medical School and Harvard University
reveals the three-dimensional structure of the human genome and answers
the thorny question of how each of our cells stows some three billion
base pairs of DNA. The work, reported in this week's issue of
Science, may also explain how cells control which stretches of DNA are
transcribed and which remain silent. Furthermore, the new technique
could allow researchers to study how gene expression changes as cells
develop or become cancerous, says Thomas Tullius, professor of
chemistry at Boston University, who was not part of the research team. "It's
a whole new view of the chromosome and its place in the cell, and it's
a view we've never had before," says Tullius, who studies the structure
of DNA. The new structural data reveal that the human genome is
organized into two separate compartments, keeping active genes
accessible while sequestering unused DNA in a denser storage
compartment. Each chromosome alternates between regions of active,
gene-rich DNA and inactive, gene-poor stretches. Collaborating
with physicists at MIT, genome scientists established that the genome
adopts an unusual organization known in mathematics as a fractal. This
architecture, called a "fractal globule," enables the cell to pack DNA
incredibly tightly while avoiding the knots and tangles that might
interfere with the cell's ability to read its own genome. Moreover, the
DNA can easily unfold and refold during gene activation, gene
repression and cell replication. "Nature's devised a stunningly
elegant solution to storing information — a super-dense, knot-free
structure," says senior author Eric Lander, director of the Broad
Institute, who is also professor of biology at MIT and professor of
systems biology at Harvard Medical School. Theoretical
biophysicist Alexander Grosberg of New York University originally
proposed a fractal globule structure for DNA in 1993. "Now it is
beautifully confirmed, which is very exciting," Grosberg says. Form follows function Just
as the 1953 discovery of the DNA double helix by James Watson and
Francis Crick revealed how genetic information is stored and copied,
the discovery of DNA's 3-D structure offers new insights into how cells
control which sections of DNA are translated into proteins. "It's
very suggestive as to how basic cellular processes are taking place, in
terms of information storage and retrieval," says co-first author of
the Science paper Erez Lieberman-Aiden, a graduate student in the
Harvard-MIT Division of Health Sciences and Technology (HST) and a
researcher in Lander's laboratory. "It gives us a lot of ideas about
how genes are turned on and off." For example, computer
simulations in the lab of MIT physicist (and HST associate professor)
Leonid Mirny demonstrated that sections of a fractal globule structure
can be easily opened up by chemical modification, suggesting that cells
could use such modifications to control transcription of related genes
located near each other. In the past, many scientists had
thought that DNA was compressed into a different architecture called an
"equilibrium globule," a configuration that is problematic because it
can become densely knotted and does not easily open up. Key to
deciphering the genome's structure was the development of the new Hi-C
technique, which permits genome-wide analysis of the proximity of
individual genes. The scientists first used formaldehyde to link
together DNA strands that are nearby in the cell's nucleus. They then
determined the identity of the neighboring segments by shredding the
DNA into many tiny pieces, attaching the linked DNA into small loops,
and performing massively parallel DNA sequencing. Lieberman-Aiden
observed that the data suggest a fractal globule. He then teamed up
with Mirny and Mirny's student Maxim Imakaev to confirm his hypothesis
and demonstrate conclusively that the Hi-C data matched fractal globule
behavior. Computer simulations further helped to reveal biologically
important features of such a DNA architecture. In future
experiments, the researchers hope to follow the development of stem
cells into mature cell types such as kidney cells, says
Lieberman-Aiden. "We want to understand how that process takes place,
because it clearly involves some 3-D remodeling of the nucleus." "picture description" Until recently, scientists theorized that DNA organized itself into a
structure known as an equilibrium globule, left. This type of structure
is highly tangled, and stretches of DNA located near each other on a
chromosome may be far apart in the 3D structure. MIT, Harvard and UMass
Medical School researchers have shown that DNA is actually organized as
a fractal globule, right, which resists knotting and allows DNA regions
on a chromosome to remain near each other in the 3D structure. Images: Leonid A. Mirny and Maxim Imakaev
Zdroj: web
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Personal genomics firms must come clean
Companies that offer analyses of future health risks
based on basic genetic tests should be more transparent about the
limitations of their predictions, says genomics pioneer Craig Venter.
He
and four colleagues have proposed guidelines for the industry after
assessing the results of scans of their own personal genomes as
provided by the Californian firms 23andMe and Navigenics .
They found the companies recorded the genetic markers consistently at
least 99.7 per cent of the time, but diverged on their assessment of
the associated health risks.
That's similar to New Scientist 's comparison earlier this year of the results of scans from 23andMe and a third company, Decode Genetics of Reykjavik, Iceland. In this case the genetic markers were consistently recorded 99.996 per cent of the time .
Beg to differ
For
four common diseases, the companies agreed for Venter and his
colleagues on whether each had a reduced, average, or increased risk.
But for seven other conditions, they came up with different answers for
at least two of the group.
The
predictions were particularly varied for the skin disease psoriasis: in
Venter's case, 23andMe put his risk at more than four times a typical
person's, whereas Navigenics said it was just 25 per cent above average.
New Scientist
also obtained divergent predictions for psoriasis – 23andMe put our
reporter's relative risk at 13 per cent below average, while Decode
suggested that he faced a mere third of the typical risk. Such
differences arise largely because the companies look at different
collections of genetic markers.
Venter , who heads his own institute
in San Diego, California, and colleagues, recommend that companies
should agree on a core set of markers with strong effects for each
disease.
They
also suggest that both companies and customers should focus attention
on the diseases with the highest risk predictions – which are likely to
remain significant even as more information accumulates .
Whole genomes
The
group argues that companies should be more transparent about the
limitations of their predictions by telling customers what proportion
of their genetic risk can be accounted for by the markers in the scans.
For
instance, 23andMe currently tells customers that about 26 per cent of
the risk of developing type 2 diabetes is due to genetic factors, but
it does not stress that the nine markers it scans for the condition only account for only a fraction of this figure . "We do have estimates, and we will consider how best to communicate them to our customers," says Andro Hsu of 23andMe.
Geneticists
still know remarkably little about how differences in people's DNA
affect health, says Venter. "My whole genome is out there and it can't
give me much more information than the personal genomics companies."
Once
several thousand people have had their genomes fully sequenced, says
Venter, what's needed is the collection of detailed health data from
all of these individuals.
Journal reference: Nature , vol 461, p 724
Zdroj: New Scientist
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Genetic seamstress uses molecular fingers to tweak DNA
THE genetic equivalent of a tailor who uses molecular
"fingers" to grab onto DNA, before snipping it apart and stitching in a
new sequence could lead to safer gene therapies.
In
principle, genetic engineering is simple, but inserting a new gene into
the right place in an organism's genome is fraught with difficulty. For
example, in a gene therapy trial for X-SCID - or "bubble-boy" disease - inserting a gene in the wrong place triggered cancer in some of the recipients.
One approach for locating and snipping DNA strands involves "zinc fingers"
- proteins that bind to DNA and can be linked together to recognise
extended stretches of DNA with very high specificity. Zinc fingers are
usually attached to enzymes called nucleases, dubbed ZFNs, which cut
both strands of DNA.
However,
the problem with this approach is that it relies on enzymes, the cell's
natural repair machinery to fix the break, and either insert a new gene
or a mutation that knocks out the function of a gene. "In some cells
these enzymes work better than in others," says Marshall Stark of the University of Glasgow, UK.
Instead,
Carlos Barbas of the Scripps Research Institute in La Jolla,
California, and his colleagues have taken viral enzymes called
recombinases and attached these to zinc fingers, called ZFRs.
While
a ZFN is essentially just a pair of scissors, the recombinase in a ZFR
both cuts and mends the break without resorting to unreliable enzymes.
Unlike
nucleases, recombinases cut a double-stranded piece of DNA and then
wait around on the exposed ends. When the intended gene, which would
have been inserted at the same time, comes along, the recombinase
recognises it, and binds the DNA to the ends, repairing the break (see diagram) .
"The advantage of a site-specific recombinase is that the enzyme does
everything," says Stark, who is also investigating the potential of
ZFRs in genetic engineering.
As
proof of principle, Barbas's team has taken human cells and inserted a
gene that their ZFR would recognise. They then used the recombinase to
insert the gene into the cells' genome. The gene was inserted correctly
in more than 98 per cent of cases, says Barbas, who presented his
results earlier this week at the Strategies for Engineered Negligible
Senescence meeting in Cambridge, UK.
Their results are promising, says Matthew Porteus
of the University of Texas in Dallas. "It will be interesting to see
how efficiently they can [target genes] to a natural site in the human
genome," he adds.
If you could target specific sequences in a genome you could introduce genes at safe places
According
to Philip Gregory of Sangamo BioSciences in Richmond, California, zinc
finger-based gene editing holds significant promise. "Efficient and
specific gene editing will be important in advancing the post genomic
era of medicine and zinc-finger based reagents will play a prominent
role," he says.
Sangamo
is testing the ability of a ZFN to disrupt the expression of a key
protein that HIV uses as a door handle to enter cells. He adds that it
is too early to say whether the recombinase fingers will prove as
useful as ZFNs.
Zdroj: New Scientist
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Better world: Screen your genes
It's debatable whether getting your genes tested can tell you anything very helpful about your health , for now at least. But it could make a huge difference to your children's.
Genetic
tests can reveal if you are a carrier of disorders such as cystic
fibrosis, sickle cell disease and spinal muscular dystrophy. In some
countries, tests for some genetic diseases are already recommended to
would-be parents, but many couples, of course, do not consult their
doctors before trying to conceive.
If
you are a carrier, various options are open to you. One is to ensure
potential partners aren't carriers, too, if you want to have children.
By promoting this approach
the Jewish organisation Dor Yeshorim has greatly reduced the incidence
of Tay-Sachs, a genetic disorder that slowly kills young children.
Another
option, where there is a risk of passing on a serious disease, is
preimplantation genetic diagnosis, or PGD, which can be used to ensure
that any children born after IVF will not suffer from the disease. Then
there is prenatal diagnosis, already widely used to screen for
non-inherited genetic disorders such as Down's syndrome.
Finally,
even if you opt for none of the above, simply knowing your child might
have a genetic disorder will help ensure they get the right treatment
from the start. In most countries, the decision, as it should be, is
yours - and the earlier you discover your children might inherit a
serious disease, the more choices you have.
Zdroj: New Scientist
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My 'non-human' DNA: a cautionary tale
"This is a strange question, but are you sure this is Homo sapiens ?"
It's
not every day that an expert queries whether your DNA is human, so when
I received this comment by email earlier this month I was somewhat
bemused.
I am not in fact the result of a coupling between human and alien, nor the product of some twisted genetic experiment. Instead, Blaine Bettinger , who blogs as The Genetic Genealogist , had been baffled by a DNA profile generated in error by deCODEme ,
a leading commercial "personal genomics" service provided by Decode
Genetics in Reykjavik, Iceland. The false profile seems to be the fault
of a software bug.
No
harm was done, but the incident serves as a cautionary tale for
personalised medicine. As we move towards a future in which readouts
from our genomes will routinely be queried by computer systems to help
doctors make important clinical decisions, similar glitches could cause
prescribing errors – with patients being given drugs at the wrong dose,
drugs that won't work, or ones that could even trigger serious side
effects in people with a particular genetic make-up.
Before
other deCODEme customers get too irate about errors in data for which
they have paid almost $1000, the bug affects only a tiny portion of the
results presented. Most importantly, the disease-risk summaries
provided by deCODEme seem to be based on the correct genetic
information.
Through the mangle
After spending hours picking through my genetic data as provided by both deCODEme and its main rival, 23andme , based in Mountain View, California, it became clear that the problem specifically affects the display in deCODEme's online genome browser of DNA markers from my mitochondria – the tiny cellular power plants that generate energy from sugars.
Mitochondrial
DNA profiles can be used to probe your maternal ancestry – which is why
I sought the help of an expert in genetic genealogy to help solve the
mystery. Bettinger's confusion suggested that I was looking at a
bizarre mangling of my own data, rather than the inadvertent
presentation of some other customer's.
To
be fair, sometimes deCODEme's genome browser displayed my mitochondrial
DNA correctly. At other times, however, a specific error-strewn profile
appeared. Of 95 mitochondrial DNA markers that I could check against
both my 23andme account and my entire dataset downloaded from the
deCODEme website, 44 displayed the wrong letter of genetic code.
Decode Genetics
is still investigating these problems. Specialists in bioinformatics
suggest that they must be caused by a bug in the software that Decode
uses to retrieve information from its database.
That's
sobering, because enthusiasts for health information technology
envisage a future in which computer systems like Decode's will query
databases holding people's DNA profiles to help doctors make decisions
on which drugs to prescribe, and at what doses.
Data overload
Meticulous
bug-checking will be needed to ensure that health IT delivers on its
promise of improving clinical decision-making and reducing human
errors. "Algorithms will need to be absolutely tested and accurate,"
says Catherine McCarty , a geneticist at the Marshfield Clinic Research Foundation in Wisconsin, which specialises in the use of electronic medical records (EMRs).
The worry, she says, is that many competing EMR systems are being developed, and not all of them have been vetted by the Certification Commission for Health Information Technology ,a non-profit body based in Chicago that runs the industry's main quality assurance scheme.
Adding
genetic information into the mix will escalate the potential for errors
because of the huge volume of data involved. My deCODEme genome scan,
for instance, contains information on more than 1.1 million DNA
markers. If in future people routinely have their entire genomes
sequenced, we will be dealing with some 3 billion data points per
person.
Even
without errors by software bugs, patients could be unduly worried and
doctors side-tracked into ordering unnecessary medical tests, as
computers highlight anomalies in people's DNA sequences that have no
clinical significance. Isaac Kohane , a specialist in health IT at Harvard Medical School, has coined a term for the problem: the incidentalome .
Given
the potential to be misled, Kohane says that it's important not to get
seduced by the apparent precision of genomic information. "We need to
be a little bit wary of genetic triumphalism," he says.
Zdroj: New Scientist
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DNA Evidence Can Be Fabricated, Scientists Show
Scientists in Israel have demonstrated that it is possible to fabricate DNA evidence, undermining the credibility of what has been considered the gold standard of proof in criminal cases. The scientists fabricated blood and saliva samples containing DNA from a person other than the donor of the blood and saliva. They also showed that if they had access to a DNA profile in a database, they could construct a sample of DNA to match that profile without obtaining any tissue from that person. “You can just engineer a crime scene,” said Dan Frumkin, lead author of the paper, which has been published online by the journal Forensic Science International: Genetics. “Any biology undergraduate could perform this.” Dr. Frumkin is a founder of Nucleix, a company based in Tel Aviv that has developed a test to distinguish real DNA samples from fake ones that it hopes to sell to forensics laboratories. The planting of fabricated DNA evidence at a crime scene is only one implication of the findings. A potential invasion of personal privacy is another. Using some of the same techniques, it may be possible to scavenge anyone’s DNA from a discarded drinking cup or cigarette butt and turn it into a saliva sample that could be submitted to a genetic testing company that measures ancestry or the risk of getting various diseases. Celebrities might have to fear “genetic paparazzi,” said Gail H. Javitt of the Genetics and Public Policy Center at Johns Hopkins University. Tania Simoncelli, science adviser to the American Civil Liberties Union, said the findings were worrisome. “DNA is a lot easier to plant at a crime scene than fingerprints,” she said. “We’re creating a criminal justice system that is increasingly relying on this technology.” John M. Butler, leader of the human identity testing project at the National Institute of Standards and Technology, said he was “impressed at how well they were able to fabricate the fake DNA profiles.” However, he added, “I think your average criminal wouldn’t be able to do something like that.” The scientists fabricated DNA samples two ways. One required a real, if tiny, DNA sample, perhaps from a strand of hair or drinking cup. They amplified the tiny sample into a large quantity of DNA using a standard technique called whole genome amplification. Of course, a drinking cup or piece of hair might itself be left at a crime scene to frame someone, but blood or saliva may be more believable. The authors of the paper took blood from a woman and centrifuged it to remove the white cells, which contain DNA. To the remaining red cells they added DNA that had been amplified from a man’s hair. Since red cells do not contain DNA, all of the genetic material in the blood sample was from the man. The authors sent it to a leading American forensics laboratory, which analyzed it as if it were a normal sample of a man’s blood. The other technique relied on DNA profiles, stored in law enforcement databases as a series of numbers and letters corresponding to variations at 13 spots in a person’s genome. From a pooled sample of many people’s DNA, the scientists cloned tiny DNA snippets representing the common variants at each spot, creating a library of such snippets. To prepare a DNA sample matching any profile, they just mixed the proper snippets together. They said that a library of 425 different DNA snippets would be enough to cover every conceivable profile. Nucleix’s test to tell if a sample has been fabricated relies on the fact that amplified DNA — which would be used in either deception — is not methylated, meaning it lacks certain molecules that are attached to the DNA at specific points, usually to inactivate genes.
Zdroj: The New York Times
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Swine flu is a man made virus ?
Je prasečí chřipka vyrobena genetickou manipulací?
Zdroj: YouTube.com
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SEQUENOM Announces Cost Cutting Initiative in Genetic Analysis Business
SEQUENOM, Inc. (NASDAQ: SQNM) today announced that as a result of the continuing weak outlook in 2009 for capital equipment sales, particularly in the USA, the
company has implemented cost cutting initiatives in the Genetic Analysis (GA) business to ensure the unit remains financially strong and approaches cash flow
breakeven. These measures are expected to generate increased operational efficiencies and reduce costs while continuing to allow SEQUENOM to serve the
needs of its current and future genetic analysis customers. In addition, SEQUENOM is also repositioning the GA business to better exploit potential
synergies with the molecular diagnostic business by focusing on developing methods and assays for translational research and patient profiling in clinical
trials. These measures are also designed to leverage the short- and longer-term potential of the company`s molecular diagnostics business, where SEQUENOM
continues to invest.
The company is decreasing its GA workforce by approximately 30 employees with immediate effect. The realignment along with other efficiencies is expected to
result in an $8 million decrease in costs in 2009 and an annualized reduction in costs of $10 million. Estimated charges of $850 thousand will be recorded in the
second quarter of 2009 in connection with one-time employee termination benefits including severance. The company will support and add resources to the GA
business unit as the economy shows improvement and revenues resume an upward trend.
"These actions are difficult but essential. While we remain optimistic that the outlook for the genetic analysis business will improve, we also need to exercise
financial prudence to ensure that our capital resources are properly allocated and utilized," said Harry Stylli, PhD, president and chief executive officer of
SEQUENOM. "We will continue to serve our traditional customers such as academic institutions focused on genotyping, methylation and gene expression. However, as
our system uniquely combines high throughput with highly quantitative capabilities, our business unit has great potential value in new and growing
markets, such as translational research, and in better exploiting the interface with the molecular diagnostics business.
"I would like to express my sincere gratitude for the contributions and commitment of all employees impacted by the workforce reduction," he added. "Our
agility as a company has allowed us to implement a strategy over the past several years to focus on the high-growth area of molecular diagnostics, and to
leverage the tremendous expertise and innovation generated by our fundamental understanding of genetics and history as a systems and applications provider in
genetic analysis. We remain well positioned to launch our innovative SEQureDx prenatal technology in June."
SEQUENOM will provide additional details associated with this initiative with the release of its first quarter 2009 financial results, which is scheduled for
April 30, 2009.
About SEQUENOM
SEQUENOM is committed to providing the best genetic analysis products that translate the results of genomic science into solutions for noninvasive prenatal
diagnostics, biomedical research, translational research and molecular medicine applications. The company's proprietary MassARRAY® system is a high-performance
(in speed, accuracy and cost efficiency) nucleic acid analysis platform that quantitatively and precisely measures genetic target material and variations.
The company has exclusively licensed intellectual property rights for the development and commercialization of noninvasive prenatal genetic tests for use
with the MassARRAY system and other platforms. SEQUENOM maintains a Web site at www.sequenom.com to which SEQUENOM regularly posts copies of its press releases
as well as additional information about SEQUENOM. Interested persons can subscribe on the SEQUENOM Web site to email alerts or RSS feeds that are sent
automatically when SEQUENOM issues press releases, files its reports with the Securities and Exchange Commission or posts certain other information to the Web
site.
SEQUENOM®, MassARRAY® and SEQureDx are trademarks of SEQUENOM, Inc.
Forward-Looking Statements
Except for the historical information contained herein, the matters set forth in this press release, including statements regarding the Company`s weak outlook in
2009 for capital equipment sales, the future financial strength and cash flow for the Company`s GA business, expected impact of the Company`s cost cutting
initiatives on operational efficiencies and costs and its ability to serve its customers, potential synergies between the Company`s GA business and its
molecular diagnostics business and the expected impact and benefits of repositioning the Company`s GA business, the short and long term potential of
the Company`s molecular diagnostics business, the expected financial impact of the Company decreasing its GA workforce, expectations regarding improvement in
the economy and Company revenues resuming an upward trend, optimism regarding the outlookfor the Company`s genomic analysis business, the Company`s ability to
ensure that sufficient capital resources are properly allocated and prioritized, the potential value of the Company`s GA business in new and growing markets such
as translational research, the Company`s expected launch of its SEQureDx prenatal technology in June, and the Company`s ability to develop and
commercialize diagnostic tests on multiple platforms, are forward-looking statements within the meaning of the "safe harbor" provisions of the Private
Securities Litigation Reform Act of 1995.These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ
materially, including the risks and uncertainties associated with the Company`s operating performance, demand for and market acceptance of the Company`s
products, services, and technologies, research and development progress, new technology and product development and commercialization particularly with
respect to new markets and for new technologies such as molecular diagnostics and laboratory developed tests, and particularly noninvasive prenatal
diagnostics and laboratory developed tests, reliance upon the collaborative efforts of other parties, competition, intellectual property protection and
intellectual property rights of others, government regulation particularly with respect to diagnostic products and laboratory developed tests, obtaining or
maintaining regulatory approvals, and other risks detailed from time to time in the Company`s SEC (U.S. Securities and Exchange Commission) filings, including
the Company`s Annual Report on Form 10-K for the year ended December 31, 2008 and other documents subsequently filed with or furnished to the SEC. These
forward-looking statements are based on current information that may change and you are cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary
statement, and the Company undertakes no obligation to revise or update any forward-looking statement to reflect events or circumstances after the issuance
of this press release.
Zdroj: Reuters.com
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Show me your DNA and I'll tell you your eye color
More and more information is being gathered about how human genes influence medically relevant traits, such as the propensity to develop a certain disease. The ultimate goal is to predict whether or not a given trait will develop later in life from the genome sequence alone (i.e. from the sequence of the bases that make up the DNA strands that store genetic information in every cell of the body).
Now, writing in the journal Current Biology a group of researchers form the Netherlands put this goal to a test using eye colour. The group around Manfred Kayser of the Erasmus University Medical Center Rotterdam showed that it can be predicted with an accuracy of over 90% whether a person has blue or brown eyes by analysing DNA from only 6 different positions of the genome.
Human eye colour, which is determined by the extent and type of pigmentation on the eye's iris, is what geneticists call a 'complex trait'. This means that several genes control which colour the eyes will ultimately have. Over the past decades a number of such 'eye-colour genes' have been identified, and people with different eye colour, will have a different DNA sequence at certain points in these genes.
Such differences are known as single nucleotide polymorphisms (SNPs). Manfred Kayser and his colleagues analysed the DNA of over 6000 Dutch people whose eye colour had been scored. They determined the sequence at 37 SNPs in 8 eye colour genes for each of these and found that the eye colour of a given individual can be predicted with over 90% confidence already with the best 6 SNPs from 6 genes, as long as the persons's eyes are blue or brown. For the intermediate colour, shown by about 10% of the people tested, the accuracy is lower at about 75%.
The implications of this study are two-fold. For one, it is a proof-of-principle that complex traits can be predicted from the genome sequence alone, provided that genes with strong effects on the trait exist and are known. This can have implications for predicting disease risks based on DNA, before the disease breaks out. In addition, these findings have direct relevance in the forensic sector. Consider a case where the only trace of the suspect is a DNA trace but the DNA profile generated does not match that of known suspects or any in the Criminal Database.
There currently is in fact one such open case in Germany where the DNA of a single woman was found at dozens of crime sites over several years. Using the approach of the new study, the eye colour of a suspect— and in principle also other traits such as hair colour — can be predicted, thus helping to find unknown suspects. Needless to say, there are also caveats, one of them is that the prediction was only tested for individuals of Dutch European descent, and, although expected, it needs to be shown that similarly high prediction accuracies are obtainable in other populations across Europe.
Also, the reliability of such DNA-based eye color prediction test currently depends on an accurate knowledge that the unknown person whose DNA was tested is of European descent, since the used SNPs are associated with eye color but have no direct functional implications as far as known. Inferring highly accurate information on European ancestry from a DNA sample is not trivial, although such research is underway as well.
Zdroj: web
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Genentech Still Asserts Roche Bid Is Too Low
Genentech executives, seeking to fend off a hostile takeover bid from Roche, said on Monday that sales of Genentech’s cancer drug Avastin might quadruple to $10 billion by 2015. The projection for Avastin sales was one of many made by the
executives at an investor meeting in an effort to show that Genentech
is worth far more than the $86.50 a share that Roche is offering for
the 44 percent of the company it does not already own.Genentech
executives, as opposed to the board, have been largely silent, at least
in public, about Roche’s offer until now. But on Monday, in a nearly
five-hour meeting with investors in New York, the executives came out
swinging, saying their company should be worth much more to Roche than
it is offering to pay.
David A. Ebersman, Genentech’s chief
financial officer, drew applause when he showed how dependent Roche
already was on Genentech. He put up a chart showing dozens of clinical
trials that Roche is conducting. When he then stripped out those
involving drugs developed by Genentech, it was as if a forest had been
denuded.
Roche, a Swiss pharmaceutical giant, first offered $89
a share, or $43.7 billion, last July, which was rejected as inadequate
by a committee of Genentech’s directors. On Feb. 9, Roche started a
tender offer at $86.50 a share, which expires on March 12. Genentech’s
board committee has urged shareholders to reject that bid.
Steven Harr, a biotechnology analyst at Morgan Stanley ,
said that Genentech’s presentation only reinforced his view that few
investors would tender their shares. “Any investor is likely to feel
better about a decision not to tender,” he said after the presentation,
adding that Genentech executives were even more positive about the
company’s growth prospects on Monday than they were in the forecasts
they provided to Roche in November.
A spokeswoman for Roche
said the company would have no comment on Genentech’s presentation. She
said Roche had already laid out its case to Genentech shareholders.
Shares of Genentech fell 4.63 percent, or $3.96. to $81.59, on a day when the markets declined.
Arthur
D. Levinson, Genentech’s chief executive, said that the growth in the
company’s earnings per share from 1998 through this year would be about
32 percent a year, faster than that of any other company with a market
value of more than $50 billion, including Apple, Oracle and various oil
producers.
The executives projected that earnings per share
could grow 18 percent a year from 2010 to 2015 and that drug sales
would reach $17 billion by then, up from $9.5 billion last year.
A
key to that is Avastin, which had sales in the United States of $2.7
billion last year based on its approvals to treat advanced colon, lung
and breast cancers. Genentech said there could be an extra $5 billion a
year in sales if Avastin could be used to treat cancer at an earlier
stage. Genentech expects results next month of a clinical trial testing
whether Avastin is effective in treating early-stage colon cancer.
Genentech’s
board has said the company is worth $112 a share based on its growth
prospects. But Roche has challenged many of the assumptions behind that
forecast, saying they were overly optimistic.
Mr. Ebersman,
Genentech’s chief financial officer, said Genentech spent two months
preparing data to address Roche’s criticisms but that Roche did not
concede on even a single point. “It wasn’t in their interest to agree
with the assumptions we had in our plan,” Mr. Ebersman said.
In his first public expression of his feelings about Roche’s offer, Dr. Levinson said he was sad and disappointed, not angry.
But
he prevented the Genentech executives from answering a question posed
by an analyst — about whether they would leave the company if Roche’s
hostile bid succeeds.
“We are not speculating on all these
what-if scenarios,” Dr. Levinson said. “If you focus on them, you are
distracted” from running the company.
Zdroj: The New York Times
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Scientists' stem cell breakthrough ends ethical dilemma
Scientists have found a way to make an almost limitless supply of
stem cells that could safely be used in patients while avoiding the
ethical dilemma of destroying embryos.
In a breakthrough that
could have huge implications, British and Canadian scientists have
found a way of reprogramming skin cells taken from adults, effectively
winding the clock back on the cells until they were in an embryonic
form.
The work has been hailed as a major step forward by
scientists and welcomed by pro-life organisations, who called on
researchers to halt other experiments which use stem cells collected
from embryos made at IVF clinics.
Sir Ian Wilmut, who led the team that cloned Dolly the Sheep and heads the MRC Centre for Regenerative Medicine
at Edinburgh University where the work was done, said: "This is a
significant step in the right direction. The team has made great
progress and combining this work with that of other scientists working
on stem cell differentiation, there is hope that the promise of
regenerative medicine could soon be met."
Stem cells have the
potential to be turned into any tissue in the body, an ability that has
led researchers to believe they could be used to make "spare parts" to
replace diseased and damaged organs and treat conditions as diverse as
Parkinson's disease, diabetes and spinal cord injury.
Because the
cells can be made from a patient's own skin, they carry the same DNA
and so could be used without a risk of being rejected by the immune
system.
Scientists showed they could make stem cells from adult
cells more than a year ago, but the cells could never be used in
patients because the procedure involved injecting viruses that could
cause cancer. Overcoming the problem has been a major stumbling block
in efforts to make stem cells fulfil their promise of transforming the
future of medicine.
Now, scientists at the universities of
Edinburgh and Toronto have found a way to achieve the same feat without
using viruses, making so-called induced pluripotent stem (iPS) cell
therapies a realistic prospect for the first time.
In 2007,
researchers in Japan and America announced they had turned adult skin
cells into stem cells by injecting them with a virus carrying four
extra genes. Because the virus could accidentally switch on cancer
genes, the cells would not be safe enough to use in patients.
In
two papers published in the journal Nature, Keisuke Kaji in Edinburgh
and Andras Nagy in Toronto, describe how they reprogrammed cells using
a safer technique called electroporation. This allowed the scientists
to do away with viruses and ferry genes into the cells through pores.
Once the genes had done their job, the scientists removed them, leaving
the cells healthy and intact.
Tests on stem cells made from human and mouse cells showed they behaved in the same as embryonic stem cells.
"I
was very excited when I found stem cell-like cells in my culture
dishes. Nobody, including me, thought it was really possible," said
Kaji. "It is a step towards the practical use of reprogrammed cells in
medicine, perhaps even eliminating the need for human embryos as a
source of stem cells."
Nagy said: "We hope that these stem cells
will form the basis for treatment for many diseases and conditions that
are currently considered incurable. We have found a highly efficient
and safe way to create new cells for the human body which avoids the
challenge of immune rejection."
Josephine Quintavalle from the lobby group Comment on Reproductive Ethics ,
which opposes embryonic stem cell research, said: "What we've got here
is something that will bring joy to the pro-life movement, a way of
obtaining embryonic-type stem cells without having to destroy human
embryos.
"There are some scientists who like to hold on to what
they've got, but I don't think people are going to waste time on
embryonic stem cells any more. Half of Europe is opposed to embryonic
stem cell research. Ideally you want something that everybody can use
without any problems. This is definitely a very, very promising way
forward and a very promising solution to the embryonic stem cell
battle."
It would be some time before the cells could be used in
patients, Wilmut said, because scientists have yet to find reliable
ways of making different tissues from stem cells.
Zdroj: Guardian UK
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Nanobot lets DNA legs do the walking
A TWO-legged molecular machine that can walk unaided along a single
strand of DNA could one day shift cargo around nanofactories. That's
the promise of a walking molecular nanobot made by researchers at the
University of Oxford. Molecular engines that walk along strands of DNA are nothing new,
but none has featured as many successful features as the Oxford team's
device. Unlike earlier attempts, their nanobot doesn't wander aimlessly
back and forth, fall off its track or destroy its track as it walks.
The team have also devised an ingenious way of powering the nanobot
that allows it to move freely.
The walker consists of
two connected feet, each made of a short sequence of DNA bases that
attach to a complementary sequence on the DNA track. However, the
sequence of bases on the track is designed so that the feet have to
compete for a foothold. That means that as one foot steps down, the
other is forced to lift off.
The power for this process
is supplied by molecules floating nearby, which react together to
release energy as long as a specific catalyst is there. The clever part
of the design is that the DNA feet themselves act as the catalyst when
they lift off the track.
The new walker is designed so
that only the back foot can lift at any one time. The walker can put
its foot back in the same place or move it forwards but it cannot take
a backward step. This also ensures that one foot is always attached to
the track.
This design solves some long-standing
problems with walking molecules. In some designs, both feet can become
detached at the same time, allowing the walker to float away; in
others, the feet are just as likely to step backwards as forwards and
so end up going nowhere.
There are challenges ahead,
however. One is that the DNA track easily gets tangled, preventing the
walker from moving. "At the moment, the nanobot has taken a single step
but our ambition is to make it move 100 nanometres or more," says
Andrew Turberfield, a physicist at the University of Oxford who led the
research. To do that, the team will have to find a way to straighten
the tracks.
So what else could the nanobot be coaxed
into doing? "We can already stop and start our motor by controlling the
amount of fuel we add, but we could add other control signals to make
walkers interact with each other, and could easily attach a cargo to
the region that links the two legs."
We could easily attach cargo to the region that links the nanobot's legs
Niles
Pierce from the California Institute of Technology in Pasadena believes
the mechanism could significantly outperform previous designs.
Zdroj: New Scientist
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Top 10 Unsolved Crimes
Jack the Ripper 1888 was a bad year to be a prostitute. Between August 7 and
November 10 of that year, five women were killed in the Whitechapel
district of London’s East End, their throats slashed and their bodies
mutilated in a way that indicated they all met their fates at the hands
of the same person. One victim’s kidney was even mailed to the police,
along with a series of taunting notes penned by someone calling himself
Jack the Ripper. Serial murder was a relatively new phenomenon and the
attacks were highly publicized. The law's failure to identify the
killer led to such an outcry that both the home secretary and London
police commissioner resigned in disgrace.
Jack the Ripper, whoever he was, has been the subject of hundreds of
books and articles. The theories surrounding his identity vary from a
covert Masonic plot to a member of the royal family. Here are the most
likely suspects:
Montague Druitt , a barrister with knowledge of human anatomy.
Rumored to be insane, he disappeared after the last murder; his body
was later found floating in the River Thames.
George Chapman , a barber who lived in Whitechapel during the
time of the murders and who was later found guilty of poisoning three
of his wives.
Aaron Kosminski , a Whitechapel resident known for his
affinity for prostitutes. He was hospitalized in an asylum several
months after the last murder.
The Zodiac Killings "I like killing people because it is so much fun." So
began one of the many encrypted letters sent to San Francisco
newspapers by the man who called himself the Zodiac. For most of 1969,
a serial killer terrorized Bay Area residents, killing five and
possibly more. It started on Dec. 20, 1968, when a couple was shot to
death while sitting in a car on a lover's lane. The killer would strike
several more times over the next 10 months, shooting a couple in a
public park, trussing up and stabbing yet another man and woman near a
peaceful lake, and shooting a cabdriver in the head.
What made
the case so fascinating, though, was the way he toyed with police and
reporters. He called in several of the murders and began to send coded
letters to newspapers, using a cross within a circle as his symbol. At
one point, he mailed in a piece of bloodied shirt to prove he was who
he claimed to be. Another time, he threatened to shoot up a school bus
full of children. The investigation went on for years. Several suspects
were considered and questioned, but to no avail. The Zodiac was never
caught. The story continues to terrorize people to this day (see David
Fincher's masterful 2007 film ).
Tupac Shakur and the Notorious B.I.G. Tupac Shakur had been shot before. The tattooed, urban poet and
self-identified thug was a central figure in the East Coast-West Coast
hip-hop rivalry. The first Tupac shooting —November 30, 1994— left the
rapper with five bullet wounds, including two in the head. Los
Angeles-based Shakur pointed his finger at a number of New York
rappers, including Sean Combs and the Notorious B.I.G. He would later
release a number of scathing rhymes against both Combs and Biggie,
including one in which he claimed to have slept with Biggie's wife.
On September 7, 1996, Tupac Shakur attended a Mike Tyson boxing
match at the MGM Grand in Las Vegas, then got into the passenger seat
of Death Row Records CEO Suge Knight’s car. At a stoplight, a white
Cadillac pulled up next to Knight’s car rolled down its windows and
fired multiple rounds into Shakur’s passenger seat. Shakur was taken to
the hospital, where he died of internal bleeding after six days. A few
months later, while waiting at a Los Angeles stoplight, the Notorious
B.I.G. met the same fate. Thanks to fanatical conspiracy theories,
uncooperative witnesses and shoddy police investigations, neither
murder case has ever been solved.
Shakur’s last album, Makaveli: The Don Killuminati/The 7 Day Theory ,
was released a month after his death. The title referenced Niccolo
Machiavelli, the Italian philosopher who was rumored to have faked his
own death (this has been largely disproved) and whose works Shakur
studied while serving an eleven-month prison sentence in 1994. So did
Tupac Shakur really die, or does he still walk among us, cloaked in a
new identity?
Nah, he died.
Tylenol Poisonings In late September/early October 1982, seven Chicago-area people died
from popping Tylenol pills laced with cyanide. Adam Janus was
experiencing chest pain. He popped a few Extra-Strength Tylenol and
collapsed an hour later. He died. That night, Janus' younger brother
and sister-in-law, grief-stricken and achey, popped a few of Adam's
Tylenol pills. They died. A 12-year old girl with a cold took some
Extra-Strength Tylenol on account of a cold. Dead. All in all, seven
were felled by the poisoned pills. Hysteria followed. A 1982 TIME story reports ,
"Police cruisers, rolling through Chicago streets Thursday afternoon
and evening, blared warnings over loudspeakers." The drug was removed
from shelves. Vague copycat incidents
— pins and needles discovered in candy bars — led several communities
to ban Halloween trick-or-treating. A gentleman was arrested after
trying to extort Johnson & Johnson for $100,000, though he was
never charged with the murders. Tamper-proof seals became the norm. The Death of Edgar Allen Poe The Raven author left New York City in 1849 bound for
Richmond, but only made it as far as Baltimore, where a passer-by
noticed the delirious and incoherent writer slouched in front of a bar
on October 3. He was taken to a nearby hospital, where he died four
days later. The local newspaper attributed his death to "congestion of
the brain," then a common euphemism for alcohol poisoning. But scholars
later discovered that rumors of his drug and alcohol abuse were greatly
exaggerated, especially by vindictive literary critics like Rufus
Wilmot Griswold. The death certificate, if it ever existed, cannot be
found. Some historians believe Poe may have suffered from
rabies, cholera or syphilis. But because he turned up on the streets
the same day as a citywide election, others argue that Poe fell victim
to "cooping," a fairly common practice back then in which corrupt
politicians paid thugs to kidnap men (especially the homeless), drug
them, disguise them, and drag them to polls all over the city or state.
This may at least explain why Poe turned up in Baltimore wearing
clothes that weren't his.
The Nicole Brown/Ron Goldman Double Murder Your objection is noted and overruled. Yes, you might have a hunch who
killed O.J. Simpson's ex-wife and her lover on June 12, 1994 in Los
Angeles. We all do. But though the court of public opinion has long
pinned this crime on "The Juice," the law says otherwise. With
circumstantial evidence piled up against him — from forensics to the
slowest, most riveting high-speed chase in history to the dubious
decision to pen a book called If I Did It — Simpson, the former
All-Star running back and B-list actor, assembled a dream team of
lawyers who convinced jurors that since the glove didn't fit, they had
to acquit. And to the disbelief of a transfixed nation, on Oct. 3,
1995, they did. Though Simpson was found liable for the deaths in a
related civil suit, the criminal matter remains unsolved. The Case of the Disembodied Feet Since August 2007, five human feet have washed ashore near
Vancouver, British Columbia. No bodies, no heads, no clothes, just feet
(4 left, 1 right), nearly all still clad in sneakers. Canadian
authorities have yet to determine how the feet ended up there or why,
though DNA tests matched one of the severed feet to a man who'd been
missing for several months. A number of theories have been tossed
around, including the possibility of foul play (though coroners
familiar with the case say ocean currents and decomposition could have
naturally separated the feet from their owners). Others speculate the
remains might belong to four unrecovered victims of a 2005 plane crash
off Quadra Island.
In June, a prankster spooked local authorities by planting a
gruesome surprise for one unwitting beachgoer — a rotting animal paw
stuffed inside an Adidas shoe. The most recent discovery was made in
November, when another foot turned up in Washington, less than 50 miles
south of the U.S.-Canadian border. As to why there have been so few
leads, police spokesperson Sharlene Brooks told CNN, "We suffer from
the 'CSI' effect: People think we can do things faster than we can.''
But a Vancouver panhandler told Bloomberg News he's already cracked the
case: "I'll bet you it was murder. You just don't find feet lying
around.''
JonBenet Ramsey Almost twelve years have passed since Dec. 26, 1996, when John
Ramsey, a wealthy software executive, found his 6-year-old daughter
JonBenet dead in the basement of their Boulder, Colo. home. Eight hours
prior, his wife Patsy had found a ransom note demanding $118,000 for
their daughter's safe return. No call ever came from a kidnapper. So
unraveled the saga of the young beauty queen whose murder has put a
cloud over her entire family, the Boulder Police Department and the
District Attorney in charge of solving the case. Investigators in
Boulder — who were dealing with the city's first murder that year —
failed to conduct a proper search of the house and even allowed friends
of the family to walk in and out of the crime scene as the family and
police waited for a ransom call.
While John's two adult
children from a previous marriage were cleared of the murder early on,
suspicion remained on the three people who were the only ones known to
be home when JonBenet was killed — her 9-year-old brother Burke and her
parents. Almost three years after the murder, Burke, now 12, was
questioned by a grand jury, but never charged. John and Patsy published
The Death of Innocence in 2000 detailing their story even as
they remained suspects in the case. In June of 2006, Patsy died of
ovarian cancer, just two months before the arrest of John Mark Karr, an
American man who had admitted to killing JonBenet, only to have the
case dropped against him two weeks later when DNA tests showed he could
not have been at the crime scene.
This past summer, prosecutors
were finally able to conclude that John and Patsy were not responsible
for their daughter's murder, but that DNA points to an "unexplained
third party." John Ramsey still retains hope that evidence will track
down his daughter's killer and finally rid his family of the stain that
continues to make its mark.
The Black Dahlia Hollywood's most famous murder case unfolded on January 15, 1947
when the raven-haired, 22-year-old actress Elizabeth Short was found
dead on Norton Avenue between 39th and Coliseum streets in Los Angeles.
Her body had been cut in half and appeared to have been drained of
blood with precision. The murderer had also cut 3-inch gashes into each
corner of her mouth, creating a spooky clown-esque smile.
Short's murder quickly became a sensation, not only because of its
location in the show biz capital, but also because the police worked in
tandem with the press to disseminate clues in hopes of locating a
suspect. Several people confessed, only to be later released for lack
of evidence. Much speculation surrounded the details of Short's life.
Grieving after the death of a man she fell in love with, she reportedly
befriended many men while frequenting jazz clubs, making it nearly
impossible to pin down who she could have been with before she died.
Her unsolved murder has spawned several movies, television specials,
and books. One such account was written by Steve Hodel who implicated
his own father, a Los Angeles doctor, as the Black Dahlia murderer. No
charges were ever filed.
The Women of Ciudad Juaréz Sometimes called the City of the Lost Girls, Juarez is a poor, Mexican
border town where hundreds (some say thousands) of women have been
raped, tortured and then killed over the past decade. Many of these
women work in the town's numerous factories or live there because it is
close to the U.S. border, which they can cross for jobs. Amnesty
International has urged Mexican authorities to make finding
perpetrators a priority. But with an ever-intensifying drug war taking
place in the country's poor neighborhoods and a government rife with
corruption, little has been done to stop the assault on the women of
Ciudad Juaréz. Marisela Ortiz, the coordinator of the non-governmental
organization Nuestras Hijas de Regreso a Casa (roughly translating to:
"May Our Daughters Return Home"), told the Latin American Herald Tribune
on Dec. 14 that the murders are largely a result of the "toll of an
internal war between the drug trafficking mafias who are fighting to
conquer the territory." The date ticker on the group's website reads:
"Today is Dec. 18, 2008 and that doesn't solve anything."
Zdroj: web
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DNA dating: Can genes help you pick a mate?
SOME people will accuse me of playing with fire. Next summer, I am
due to marry Nic, my boyfriend of two and a half years. We have plenty
in common, get on famously, and I have a strong desire to kiss him
whenever I see him. But recent events have left a niggling doubt in my
mind.
It started with a recent paper I read. It suggested that
taking hormonal contraceptives (as I have for many years) affects your
sense of smell, which is a key factor in finding Mr Right (Proceedings of the Royal Society B , vol 275, p 2715 ).
Then I received a press release from a company called ScientificMatch ,
based in Florida, which offers to match couples according to
scent-related aspects of their DNA profiles. By hooking you up with
your biological match, rather than someone ...
Zdroj: New Scientist
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Fossett joins the many mysteries of the Sierras
By Alan Levin, USA TODAY
The mystery of Steve Fossett is most likely solved, but the gray granite peaks of the Sierra Nevada may never give up the secrets they hold of missing aviators and long ago wrecked planes.
Searchers spotted Fossett's battered single-engine plane Wednesday night, more than a year after he took off from a Nevada ranch. Wreckage indicated a high-speed impact at about 10,000 feet. Small pieces of human remains were found with the wreckage, said National Transportation Safety Board Chairman Mark Rosenker.
The location — far from the main search areas farther north — didn't surprise the amateur sleuths who spend years in search of missing planes in these mountains.
"The Sierra probably holds the majority of the airplanes that weren't found for a while due to its remoteness and its ruggedness," says Craig Fuller, who studies plane crashes. He runs a website called Aviation Archaeological Investigation and Research.
Unforgiving terrain
The mountain range, which runs up California's eastern side and has the highest peak in the continental U.S., has been the backdrop of many aviation mysteries.
An Air Force pilot who bailed out of his jet in 1957 survived for weeks in the backcountry only to be unjustly accused of faking his story after he was rescued. A father spent 14 years combing the mountains in search of the bomber that his son had co-piloted. A World War II fighter plane crashed within a mile of where the pilot parachuted to safety in 1941 but has never been found despite dozens of searches.
"When you are looking for an airplane like Fossett's, it's not looking for a needle in one haystack. It's like looking for a needle in many haystacks," says G. Pat Macha, a retired high school teacher who has spent 35 years searching for plane wrecks.
Fossett, 63 when he died, left a ranch in Nevada owned by hotel magnate Barron Hilton on the morning of Sept. 3, 2007, for a flight in a Bellanca Super Decathlon propeller plane. He was looking for dry lake beds on which to try to break the land speed record in a rocket-propelled car.
He never filed a flight plan, which was routine for small private planes in that remote section of Nevada. So it's not known how he ended up flying about 90 miles south of the ranch over the pine forests and massive rock formations of the Sierras.
Fossett, an adventurer inducted into the National Aviation Hall of Fame, was an experienced pilot. But his flight over the Sierras had risks.
"We do have a higher number of accidents because the terrain is less forgiving," said Bruce Landsberg, executive director of the Aircraft Owners and Pilots Association's Air Safety Foundation.
At 10,000 feet, his plane would have been short on power, Landsberg said. According to local pilots, that section of the Sierras is known for its rough winds. A downdraft could easily have pushed the plane down faster than it was capable of climbing, Landsberg said. Weather reports that day reported gusty winds.
Mountains are 'brutal'
Lt. David Steeves made it out of the Sierra alive after his T-33 trainer jet crashed. He lived for 54 days in the wilderness after ejecting and making his way to an unoccupied cabin.
Soon after his rescue, people began to doubt his story. Where was the wreck, they asked.
Steeves died in 1965 in a small-plane crash in Idaho. It wasn't until 1977 that Boy Scouts found the canopy of his jet. To this day, the wreckage has never been located, Macha said.
In 1943, a B-24 bomber crashed in the mountains. Co-pilot 2nd Lt. Robert Hester's father, Clinton, was determined to find the plane. "He basically spent every summer that he was physically able hiking in the Sierras looking for his son," Fuller said. In 1960, a year after Clinton Hester died, a survey team found the bomber in a remote lake. It's now known as Hester Lake.
Lt. Leonard C. Lydon parachuted to safety in 1941 after his Army fighter squadron got lost over the mountains. His P-40 fell within a mile of where he landed in the remote Sequoia and Kings Canyon national parks, Macha says. "To this day, nobody has been able to come up with (the plane)," he says. "But when you see the geography, it is brutal and mind boggling."
Zdroj: USA Today
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DNA firms step up security over bioterrorism threat
A GROUP of "designer DNA" companies is stepping up security to counter fears that terrorists could order the genes needed to make a deadly virus. In 2005, New Scientist reported that some gene synthesis companies were not checking their orders for potentially dangerous DNA sequences. Since then, the US National Science Advisory Board for Biosecurity has called for better screening. Now the Industry Association of Synthetic Biology (IASB) says that its members will carry a seal of approval on their websites confirming that they do screen their orders. This is to encourage researchers to order DNA only from these companies, and put pressure on the minority of firms that cut costs by not screening to change. IASB members will cooperate to improve the software used to identify suspicious orders and will set up a secure database detailing which DNA sequences make pathogens highly virulent. "The fact that they're going to share their experiences is really important," says Stephen Maurer, a lawyer at the University of California, Berkeley, who helped write the industry guidelines.
Zdroj: New Scientist
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Four artificial new letters for the DNA alphabet
A NEW type of artificial DNA may form the basis of minuscule electronic devices.
Natural
DNA is constructed using four bases, which form the "letters" of the
genetic code. Now Masahiko Inouye and his colleagues at the University
of Toyama in Japan have used DNA synthesis equipment to stitch together
four new artificial bases inside the sugar-based backbone of a DNA
molecule (Journal of the American Chemical Society , DOI: 10.1021/ja801058h ).
The
artificial DNA is more stable than natural DNA, which may make it a
good candidate for turning into molecular electronic wires, able to
conduct electrons along their length.
So
far the team has made only short strands of artificial DNA, around 100
bases long. But Inouye plans to experiment with naturally occurring
enzymes, both to make longer strands of the molecule, and to make it
copy itself, just like regular DNA.
Combining
natural and unnatural bases could produce a whole range of interesting
molecules, suggests Olav Schiemann, a biochemist at the University of
St Andrews in the UK. "Having four unnatural bases gives you a lot more
options for using these molecules as nanodevices," he says.
Zdroj: New Scientist
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DNA to track UK-Russia migration
A DNA survey has been launched to trace the descendants of Britons who settled in Russia hundreds of years ago.
Though largely unknown in the UK, this eastward history of British migration is well acknowledged in Russia.
Russians bearing the surname Lermontov, for example, claim descent from a Scottish soldier captured in the 17th Century.
The new survey will test whether this story, along with similar ones, are backed up by genetic data.
The Russian-British project is being led by Professor Bryan Sykes, founder of DNA analysis service Oxford Ancestors.
"An academic colleague made reference to Russian families who claimed a
British progenitor, and, even though they could not speak a word of
conversational English, were able to recite fragments of British nursery
rhymes and Scottish songs," Professor Sykes explained.
These traditions were apparently transmitted orally from one generation to the next.
Apart from Lermontov, surnames to be analysed during the course of the
project will include the Greig and Crichton families in Moscow, a family
of Reads in St Petersburg (a Nikolai Read was commander of Russian
forces in the Caucusus during the mid-19th Century), and Smytovs.
Britons may have settled in Russia for many reasons. British mercernaries fighting in European wars are well-attested.
And between the 13th and 17th Centuries, there were strong trading links
between Britain and the Baltic via the Hanseatic League - an alliance
of trading guilds.
The surname Lermontov supposedly derives from the Scottish surname
Learmonth (or one of its variants such as Learmont, Learmond or
Learmouth).
One notable bearer was Mikhail Yuryevich Lermontov (1814 - 1841), one of Russia's foremost poets.
Lermontov was born in Moscow to a respectable family who traced descent
from Scottish Learmonths. One of these, recorded in Russian records as
Peter Lermontoff, settled in the country in the early 17th Century after
being captured by the Russian army.
However, despite exhaustive searches by Russian literary historians and
members of the family, it has been impossible to locate records linking
Peter Lermontoff back to Scotland.
Paternal line
Oxford Ancestors is currently seeking participants for the genetic study.
"We want to see whether the Lermontovs and the Learmounts are one and the same," Professor Sykes told the BBC News website.
"That is just the kind of thing we can check with the Y chromosome."
The Y chromosome is a package of genetic material normally found only in
males. It is passed down from father to son, more or less unchanged,
just like a surname.
But over many generations, the Y chromosome accumulates small changes in its DNA sequence.
This generates a variety of distinctive male lineages in human
populations. Studying the relationships between these different lineages
can help scientists reconstruct genealogical trees and even tell them
about ancient population movements.
Sharing a surname also significantly raises the likelihood of sharing
the same type of Y chromosome, with the link getting stronger as the
surname gets rarer.
Unusual find
If the Russian Lermontovs and the Scottish Learmounts are related, they
should share signature mutations on their male chromosome that point to a
common ancestry.
"We hope to take DNA samples from a few people with the same name and
then we'll be able to identify a common chromosome in the Scottish
Learmonts," the University of Oxford geneticist explained.
"The hope is that it would be an unusual chromosome, so when we saw it
somewhere else - Russia, for example - we could be pretty sure that was
because of common ancestry."
Professor Sykes, whose paperback book Blood of the Isles traces the
ancestral roots of the British, explained: "We've done this many times
in Britain looking at different surnames that seem to have a common
origin from their spelling; sometimes they do and sometimes they don't."
Zdroj: BBC
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