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Researchers disagree over the whens and wheres of canine domestication
Les Hirondelles Photography/Flickr/Getty Images
Scientists investigating the transformation of wolves into dogs are behaving a bit like the animals they study, as disputes roil among those using genetics to understand dog domestication.
In recent months, three international teams have published papers comparing the genomes of dogs and wolves. On some matters such as the types of genetic changes that make the two differ the researchers are more or less in agreement. Yet the teams have all arrived at wildly different conclusions about the timing, location and basis for the reinvention of ferocious wolves as placid pooches. Its a sexy field, says Greger Larson, an archeogeneticist at the University of Durham, UK. He has won a 950,000 (US$1.5-million) grant to study dog domestication starting in October. Youve got a lot of big personalities, a lot of money, and people who want to get their Nature paper first.
In January, Erik Axelsson and Kerstin Lindblad-Toh, geneticists at Uppsala University in Sweden, and their colleagues reported in Nature that genes involved in the breaking down of starch seemed to set domestic dogs apart from wild wolves. In the paper and in media interviews, the researchers argued that dog domestication was catalyzed by the dawn of agriculture around 10,000years ago in the Middle East, as wolves began to loiter around human settlements and rubbish heaps (see Nature http://doi.org/mv4; 2013).
But Larson, who has worked with Lindblad-Toh on other projects, says that their claim is dubious. He notes that bones that look similar to those of domestic dogs predate the Neolithic revolution by at least several thousand years, so domestication must have occurred before then. Why waste space [in a paper] saying something that is patently untrue? he says.
Axelsson concedes that the changes in starch digestion in dogs could have occurred after they were domesticated. But he also counters that the Neolithic era lasted for thousands of years, and that dogs may have been domesticated during the earliest steps towards agrarian life when human hunter-gatherers settled down and began eating more starch-rich wild plants.
A second study, published last month in Nature Communications, argues that dogs were domesticated 32,000years ago when they began scavenging with Palaeolithic humans in southern China. A team led by Ya-ping Zhang at the Kunming Institute of Zoology in China drew that conclusion from studying the whole genomes of several grey wolves, modern European dog breeds and indigenous Chinese dogs.
But Larson says that there is no evidence to suggest that wolves ever lived in southern China, so how do you domesticate a wolf if there arent any? And Jean-Denis Vigne, an archeozoologist at the National Museum of Natural History in Paris, agrees, noting that in earlier work, Zhangs team completely ignored what has been published, even in the frame of genetics.
Peter Savolainen, a geneticist at the KTH Royal Institute of Technology in Solna, Sweden, who co-authored the Nature Communications paper, argues that Chinese scientific literature suggests that wolves did once live south of Chinas Yangtze River, but have since become extinct. But he acknowledges that the date that his team reported like all molecular dating efforts relies on several assumptions, such as the number of genetic mutations that develop in each generation.
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As the justices prepare to hear arguments in the Myriad Genetics case, observers are debating the impact of the outcome on personalized medicine and whole-genome sequencing
Flickr/Be-Younger.com
When Daniel Weaver pitches Genformatic to potential investors, he feels obliged to note a future legal uncertainty. The two-year-old company, based in Austin, Texas, offers whole-genome sequencing and analysis to researchers and physicians, with plans to apply the technology to medical diagnostics. But Weaver fears that the company could become ensnared in a thicket of thousands of patents. Who knows how much it would cost in legal fees just to sort through that? he says.
Weaver and others in his line of business are looking to the US Supreme Court to prune that thicket. On 15 April, the court will hear arguments in a long-running lawsuit intended to answer one question: are human genes actually patentable? Yet the implications of the courts decision expected by the end of June may be narrower for business and medicine than many people hope and think. The case is limited to patents that cover the sequence of a gene, rather than methods used to analyze it (see A plethora of patents). Symbolically, this case is a pretty big deal, says Robert Cook-Deegan, a policy researcher at Duke University in Durham, North Carolina. But the practical consequences of it are limited.
The case, Association for Molecular Pathology v. Myriad Genetics, tackles the validity of patents owned by Myriad Genetics, a medical diagnostics company based in Salt Lake City, Utah, on isolated DNA that encompasses the human genes BRCA1 and BRCA2. Certain forms of these genes increase the risk of breast, ovarian and other cancers. Myriad says that its patents are necessary to protect its investment in research. But physicians and patients charge that the intellectual-property restrictions have limited development of and access to medical tests based on the genes. In 2009, the American Civil Liberties Union and the Public Patent Foundation, both based in New York, sued Myriad. The case has been rumbling through the courts ever since.
To many in biotechnology, it has ramifications beyond specific genes. The case highlights concerns that a network of individual gene patents could threaten the future of personalized medicine and whole-genome sequencing by blocking companies and clinicians from reporting a patients genetic risk factors for different diseases. Its as if somebody had a patent on the X-ray images of the pelvic region of a human being, says Weaver. You could administer the test, but you wouldnt be able to inform the patient about that region. Its crazy.
By some estimates, the number of patents on human DNA is indeed extensive. In 2005, researchers reported that 20% of human genes had been patented. Two weeks ago, another team raised that estimate to at least 41%. But some dispute these numbers and their implications. Christopher Holman, a law professor at the University of Missouri-Kansas City, read through 533 of the 4,270 patents referenced in the 2005 study, and found that more than one-quarter were unlikely to limit genetic testing. The literature is full of this kind of problem, he says.
His analysis was backed up by Nicholson Price, an academic fellow at Harvard Law School in Cambridge, Massachusetts, who found that few, if any, DNA patents would be infringed by companies or clinics sequencing whole genomes of individuals for medical insight. Many, for example, apply only to the selective isolation of specific stretches of DNA, says Price, whereas whole-genome sequencing is an untargeted sweep of the entire genome.
Myriads contested patents are part of a dying breed, says David Resnick, a patent attorney at the law firm Nixon Peabody in Boston, Massachusetts. They were filed in 1995, before much of the human genome was sequenced and put into the public domain. Many other US gene patents issued before the human genome was sequenced are no longer enforced, because the companies that hold them have stopped paying maintenance fees. This case is a conversation we should have had 20 years ago, says Resnick. Its moot now.
Cook-Deegan thinks that whole-genome approaches may still be threatened if courts interpret patent claims broadly. Christopher Mason, a genomics researcher at Weill Cornell Medical College in New York, says that companies and clinics should not have to bear the risk of a court case. If youre so sure those patents wont be a problem, he says, when I get sued, youll pay my court fees.
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Supreme Court Set to Hear Arguments on Whether Human Genes Can Be Patented
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A look at some of the most promising medical devices now in development
Photographs by Dan Saelinger
Over the past few years researchers have taken advantage of unprecedented advances in biology, electronics and human genetics to develop an impressive new tool kit for protecting and improving human health. Sophisticated medical technology and complex data analysis are now on the verge of breaking free of their traditional confines in the hospital and computer lab and making their way into our daily lives.
Physicians of the future could use these tools to monitor patients and predict how they will respond to particular treatment plans based on their own unique physiology, rather than on the average response rates of large groups of people in clinical trials. Advances in computer chip miniaturization, bioengineering and material sciences are also laying the groundwork for new devices that can take the place of complex organs such as the eye or pancreasor at least help them to function better.
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ATLANTA Fighting hereditary disease among Jews is the aim of a multi-state public health initiative launched today, called JScreen. The JScreen program (www.jscreen.org), is a non-profit, community-based public health initiative managed by Emory University School of Medicines Department of Human Genetics. It provides at-home genetic screening and private counseling for people with Jewish lineage to determine their risk for hereditary diseases that could be passed to their children.
JScreen is a collaboration among clinical geneticists, socially minded businesses and nonprofits to provide everyday people with a ready access point to cutting-edge genetic testing technology, patient education and genetic counseling services.
Todays geneticists have identified genetic markers for 19 genetic diseases that are more common in the Jewish-Ashkenazi community, including Tay-Sachs and Canavan disease. The carriers are healthy but they can pass the diseases along to their children. Couples who are both carriers can risk unknowingly having children with one of these diseases. JScreen also offers an expanded panel, useful for couples of mixed descent and interfaith couples, which screens for a total of 80 diseases.
By leveraging advances in genetic testing and online education that allow people to be screened in the comfort of their homes, we are removing barriers to allow more people to be screened, said Patricia Zartman Page, JScreen senior director at the Emory School of Medicines Department of Human Genetics.
JScreen makes testing for common genetic diseases simple providing an easy-to-use at-home saliva test that gives people who are planning to have children an unprecedented understanding of their own genetic makeup and risks relating to their childrens health. If a person or couples risk is elevated, genetic counselors from Emory University School of Medicine will privately address their results, options and resources to help ensure a healthy pregnancy and healthy baby.
Most of the time, we are able to reassure couples that their future children are not at increased risk for these devastating diseases, said Karen Arnovitz Grinzaid, JScreen senior director at the Emory School of Medicines Department of Human Genetics. When we dofind a carrier couple, we offer a variety of options to help them have healthy children. Without screening, the couples would not have known they were at risk.
For more information, visit http://www.JScreen.org.
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JScreen public health initiative fights Jewish genetic diseases
The breakthrough might set up another showdown about cloning for therapeutic purposes
OHSU Photos
From Nature magazine
It was hailed some 15 years ago as the great hope for a biomedical revolution: the use of cloning techniques to create perfectly matched tissues that would someday cure ailments ranging from diabetes to Parkinsons disease. Since then, the approach has been enveloped in ethical debate, tainted by fraud and, in recent years, overshadowed by a competing technology. Most groups gave up long ago on the finicky core method production of patient-specific embryonic stem cells (ESCs) from cloning. A quieter debate followed: do we still need therapeutic cloning?
A paper published this week by Shoukhrat Mitalipov, a reproductive biology specialist at the Oregon Health and Science University in Beaverton, and his colleagues is sure to rekindle that debate. Mitalipov and his team have finally created patient-specific ESCs through cloning, and they are keen to prove that the technology is worth pursuing.
Therapeutic cloning, or somatic-cell nuclear transfer (SCNT), begins with the same process used to create Dolly, the famous cloned sheep, in 1996. A donor cell from a body tissue such as skin is fused with an unfertilized egg from which the nucleus has been removed. The egg reprograms the DNA in the donor cell to an embryonic state and divides until it has reached the early, blastocyst stage. The cells are then harvested and cultured to create a stable cell line that is genetically matched to the donor and that can become almost any cell type in the human body.
Many scientists have tried to create human SCNT cell lines; none had succeeded until now. Most infamously, Woo Suk Hwang of Seoul National University in South Korea used hundreds of human eggs to report two successes, in 2004 and 2005. Both turned out to be fabricated. Other researchers made some headway. Mitalipov created SCNT lines in monkeys in 2007. And Dieter Egli, a regenerative medicine specialist at the New York Stem Cell Foundation, successfully produced human SCNT lines, but only when the eggs nucleus was left in the cell. As a result, the cells had abnormal numbers of chromosomes, limiting their use.
Monkeying around Mitalipov and his group began work on their new study last September, using eggs from young donors recruited through a university advertising campaign. In December, after some false starts, cells from four cloned embryos that Mitalipov had engineered began to grow. It looks like colonies, it looks like colonies, he kept thinking. Masahito Tachibana, a fertility specialist from Sendai, Japan, who is finishing a 5-year stint in Mitalipovs laboratory, nervously sectioned the 1-millimetre-wide clumps of cells and transferred them to new culture plates, where they continued to grow evidence of success. Mitalipov cancelled his holiday plans. I was happy to spend Christmas culturing cells, he says. My family understood.
The success came through minor technical tweaks. The researchers used inactivated Sendai virus (known to induce fusion of cells) to unite the egg and body cells, and an electric jolt to activate embryo development. When their first attempts produced six blastocysts but no stable cell lines, they added caffeine, which protects the egg from premature activation.
None of these techniques is new, but the researchers tested them in various combinations in more than 1,000 monkey eggs before moving on to human cells. They made the right improvements to the protocol, says Egli. Its big news. Its convincing. I believe it.
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Patient-Specific Human Embryonic Stem Cells Created by Cloning
An international team led by researchers at the Broad Institute and Massachusetts General Hospital (MGH) has identified mutations in a gene that can reduce the risk of developing type 2 diabetes, even in people who have risk factors such as obesity and old age. The results focus the search for developing novel therapeutic strategies for type 2 diabetes; if a drug can be developed that mimics the protective effect of these mutations, it could open up new ways of preventing this devastating disease.
Type 2 diabetes affects over 300 million people worldwide and is rising rapidly in prevalence. Lifestyle changes and existing medicines slow the progression of the disease, but many patients are inadequately served by current treatments. The first step to developing a new therapy is discovering and validating a "drug target" -- a human protein that, if activated or inhibited, results in prevention and treatment of the disease.
The current study breaks new ground in type 2 diabetes research and guides future therapeutic development in this disease. In the new study, researchers describe the genetic analysis of 150,000 patients showing that rare mutations in a gene called SLC30A8 reduce risk of type 2 diabetes by 65 percent. The results were seen in patients from multiple ethnic groups, suggesting that a drug that mimics the effect of these mutations might have broad utility around the globe. The protein encoded by SLC30A8 had previously been shown to play an important role in the insulin-secreting beta cells of the pancreas, and a common variant in that gene was known to slightly influence the risk of type 2 diabetes. However, it was previously unclear whether inhibiting or activating the protein would be the best strategy for reducing disease risk -- and how large an effect could be expected.
"This work underscores that human genetics is not just a tool for understanding biology: it can also powerfully inform drug discovery by addressing one of the most challenging and important questions -- knowing which targets to go after," said co-senior author David Altshuler, deputy director and chief academic officer at the Broad Institute and a Harvard Medical School professor at Massachusetts General Hospital.
The use of human genetics to identify protective mutations holds great potential. Mutations in a gene called CCR5 were found to protect against infection with HIV, the virus that causes AIDS; drugs have been developed that block the CCR5 protein. A similar protective association for heart disease set off a race to discover new cholesterol-lowering drugs when mutations in the gene PCSK9 were found to lower cholesterol levels and heart disease risk. The new type 2 diabetes study, which appears this week in Nature Genetics, suggests that CCR5 and PCSK9 are likely just the beginning but that it will take large numbers of samples and careful sleuthing to find additional genes with similar protective properties.
The Nature Genetics study grew out of a research partnership that started in 2009 involving the Broad Institute, Massachusetts General Hospital, Pfizer Inc., and Lund University Diabetes Centre in Sweden, which set out to find mutations that reduce a person's risk of type 2 diabetes. The research team selected people with severe risk factors for diabetes, such as advanced age and obesity, who never developed the disease and in fact had normal blood sugar levels. They focused on a set of genes previously identified as playing a role in type 2 diabetes and used next-generation sequencing (then a new technology) to search for rare mutations.
The team identified a genetic mutation that appeared to abolish function of the SLC30A8 gene and that was enriched in non-diabetic individuals studied in Sweden and Finland. The protection was surprising, because studies in mice had suggested that mutations in SLC30A8 might have the opposite effect -- increasing rather than decreasing risk of type 2 diabetes. However, because this particular genetic variation was exceedingly rare outside of Finland, it proved difficult to obtain additional evidence to corroborate the initial discovery by the Broad/MGH/Pfizer Inc./Lund team.
Then, in 2012, these unpublished results were shared with deCODE genetics, who uncovered a second mutation in an Icelandic population that also appeared to abolish function of the gene SLC30A8. That mutation independently reduced risk for type 2 diabetes and also lowered blood sugar in non-diabetics without any evident negative consequences.
"This discovery underscores what can be accomplished when human genetics experts on both sides of the Atlantic come together to apply their craft to founder populations, enabling us to find rare mutations with large effects on disease risk," said Kari Stefannson, CEO of deCODE genetics.
Finally, the team set out to ask if the effects of SLC30A8 protective mutations were limited to the two mutations found in populations in Finland and Iceland. As part of the NIH-funded T2D-GENES Project, chaired by Mike Boehnke at the University of Michigan, the Broad Institute had performed sequencing of 13,000 samples drawn from multiple ethnicities. The T2D-GENES Project joined the collaboration, found ten more mutations in the same gene, and again saw a protective effect. Combining all the results confirmed that inheriting one copy of a defective version of SLC30A8 led to a 65 percent reduction in risk of diabetes.
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March 3, 2014
Brett Smith for redOrbit.com Your Universe Online
A massive new study from a team of international researchers has identified mutations in a gene that can significantly reduce the risk of developing type 2 diabetes regardless of risk factors such as old age and being overweight. Seen in patients from multiple ethnic groups, the results showed a drug that imitates the influence of these mutations could be effectively used around the world.
In the study published in Nature Genetics the genetic evaluation of 150,000 patients showed that uncommon mutations in a gene called SLC30A8 scale back risk of type 2 diabetes by 65 percent. In previous research, the protein produced by SLC30A8 had been shown to play a critical role in the insulin secretion in the pancreas, and a typical variant in that gene was known to affect the risk of type 2 diabetes.
This work underscores that human genetics is not just a tool for understanding biology: it can also powerfully inform drug discovery by addressing one of the most challenging and important questions knowing which targets to go after, said study author David Altshuler, a Harvard Medical School professor at Massachusetts General Hospital.
To find mutations that reduce a persons probability of type 2 diabetes, the study team looked at participants with acute risk factors for diabetes, such as old age and obesity, who had not developed the disease and had healthy blood sugar levels. The team focused on a set of genes recognized earlier as playing a role in type 2 diabetes and looked for uncommon mutations.
They were able to find a genetic mutation that knocked out function of the SLC30A8 gene and that was highly prevalent in non-diabetic participants from Sweden and Finland. The protection against the disease was surprising, because scientific studies in mice had indicated that mutations in SLC30A8 might have the reverse effect increasing risk of type 2 diabetes. However, because this specified genetic variation was exceedingly uncommon outside of Finland, it proved difficult to obtain added evidence to corroborate the primary find.
These unpublished findings the result of a collaboration between American and Swedish scientists were shared with a group from deCODE genetics, a biopharmaceutical company based in Reykjavk, Iceland. The company researchers then found a subsequent mutation in an Icelandic population. The second mutation independently decreased risk for type 2 diabetes and decreased blood sugar in non-diabetics without apparent unfavorable effects.
Finally, the joint study team was able to identify ten more protective mutations in the same gene. With all the mutations considered together, one copy of a defective version of SLC30A8 was shown to have a 65 percent reduction in risk of diabetes.
This discovery underscores what can be accomplished when human genetics experts on both sides of the Atlantic come together to apply their craft to founder populations, enabling us to find rare mutations with large effects on disease risk, said Kari Stefannson, CEO of deCODE genetics.
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Genetic Mutation Found That Lowers Odds Of Developing Diabetes
PUBLIC RELEASE DATE:
2-Mar-2014
Contact: Haley Bridger hbridger@broadinstitute.org Broad Institute of MIT and Harvard
An international team led by researchers at the Broad Institute and Massachusetts General Hospital (MGH) has identified mutations in a gene that can reduce the risk of developing type 2 diabetes, even in people who have risk factors such as obesity and old age. The results focus the search for developing novel therapeutic strategies for type 2 diabetes; if a drug can be developed that mimics the protective effect of these mutations, it could open up new ways of preventing this devastating disease.
Type 2 diabetes affects over 300 million people worldwide and is rising rapidly in prevalence. Lifestyle changes and existing medicines slow the progression of the disease, but many patients are inadequately served by current treatments. The first step to developing a new therapy is discovering and validating a "drug target" a human protein that, if activated or inhibited, results in prevention and treatment of the disease.
The current study breaks new ground in type 2 diabetes research and guides future therapeutic development in this disease. In the new study, researchers describe the genetic analysis of 150,000 patients showing that rare mutations in a gene called SLC30A8 reduce risk of type 2 diabetes by 65 percent. The results were seen in patients from multiple ethnic groups, suggesting that a drug that mimics the effect of these mutations might have broad utility around the globe. The protein encoded by SLC30A8 had previously been shown to play an important role in the insulin-secreting beta cells of the pancreas, and a common variant in that gene was known to slightly influence the risk of type 2 diabetes. However, it was previously unclear whether inhibiting or activating the protein would be the best strategy for reducing disease risk and how large an effect could be expected.
"This work underscores that human genetics is not just a tool for understanding biology: it can also powerfully inform drug discovery by addressing one of the most challenging and important questions knowing which targets to go after," said co-senior author David Altshuler, deputy director and chief academic officer at the Broad Institute and a Harvard Medical School professor at Massachusetts General Hospital.
The use of human genetics to identify protective mutations holds great potential. Mutations in a gene called CCR5 were found to protect against infection with HIV, the virus that causes AIDS; drugs have been developed that block the CCR5 protein. A similar protective association for heart disease set off a race to discover new cholesterol-lowering drugs when mutations in the gene PCSK9 were found to lower cholesterol levels and heart disease risk. The new type 2 diabetes study, which appears this week in Nature Genetics, suggests that CCR5 and PCSK9 are likely just the beginning but that it will take large numbers of samples and careful sleuthing to find additional genes with similar protective properties.
The Nature Genetics study grew out of a research partnership that started in 2009 involving the Broad Institute, Massachusetts General Hospital, Pfizer Inc., and Lund University Diabetes Centre in Sweden, which set out to find mutations that reduce a person's risk of type 2 diabetes. The research team selected people with severe risk factors for diabetes, such as advanced age and obesity, who never developed the disease and in fact had normal blood sugar levels. They focused on a set of genes previously identified as playing a role in type 2 diabetes and used next-generation sequencing (then a new technology) to search for rare mutations.
The team identified a genetic mutation that appeared to abolish function of the SLC30A8 gene and that was enriched in non-diabetic individuals studied in Sweden and Finland. The protection was surprising, because studies in mice had suggested that mutations in SLC30A8 might have the opposite effect increasing rather than decreasing risk of type 2 diabetes. However, because this particular genetic variation was exceedingly rare outside of Finland, it proved difficult to obtain additional evidence to corroborate the initial discovery by the Broad/MGH/Pfizer Inc./Lund team.
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When it comes to developmental disorders of the brain, men and women are not created equal.
Decades of research have shown that males are at far greater risk for neurodevelopmental disorders such as autism spectrum disorder (ASD) than females. Boys, on average, are five times more likely to have autismthan girls.What causes this disparity has largely remained unknown.
Now scientists haveuncovered compelling genetic evidence to explain why the biological scales arent balanced.
According to a team of geneticists in the U.S. and Switzerland,it all boils down to whats called the female protective model. This suggests that girls have a higher tolerance for harmful genetic mutations and therefore require a larger number ofthem than boys to reach the diagnostic threshold of a developmental disorder. With identical genetic mutations, then, a boy could show symptoms of ASD while a girl could show none.
But because the female mutation threshold is higher, when girls are diagnosed with ASD, they tend to fall on the more severe end of the spectrum.
Researchers believe the same dynamic could explain why more boys are diagnosed withADHD, intellectual disabilities and schizophrenia. The findings were published Thursday in the American Journal of Human Genetics.
Geneticists analyzed DNA samples from 16,000 boys and girls with neurodevelopmental disorders.They found that, on average, females diagnosed with ASD had 1.3 to 3 times more harmful genetic alterations than males diagnosed with the disorder.
The findings suggest that as the male brain develops, smaller and more subtle genetic changes can trigger autism spectrum disorders. Female brains require a greater number or severity of mutations before showing symptoms, so their symptoms tend to be worse.
Theres no application in terms of treatment, said study author Sbastien Jacquemont of University Hospital of Lausanne in Switzerland, but it does help understand the inheritance dynamics in families.
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PUBLIC RELEASE DATE:
27-Feb-2014
Contact: Mary Beth O'Leary moleary@cell.com 617-397-2802 Cell Press
Males are at greater risk for neurodevelopmental disorders, such as autism spectrum disorder (ASD), than females, but the underlying reasons have been unclear. A large cohort study published by Cell Press on February 27th in the American Journal of Human Genetics provides compelling evidence in support of the "female protective model," which proposes that females require more extreme genetic mutations than do males to push them over the diagnostic threshold for neurodevelopmental disorders.
"This is the first study that convincingly demonstrates a difference at the molecular level between boys and girls referred to the clinic for a developmental disability," says study author Sbastien Jacquemont of the University Hospital of Lausanne. "The study suggests that there is a different level of robustness in brain development, and females seem to have a clear advantage."
A gender bias in the prevalence of neurodevelopmental disorders has been reported for ASD, intellectual disability, and attention deficit hyperactivity disorder. Some researchers have suggested that there is a social bias that increases the likelihood of diagnosis in males, whereas others have proposed that there are sex-based differences in genetic susceptibility. However, past studies investigating biological explanations for the gender bias have produced inconclusive results.
To examine this question, Jacquemont teamed up with Evan Eichler of the University of Washington School of Medicine to analyze DNA samples and sequencing data sets of one cohort consisting of nearly 16,000 individuals with neurodevelopmental disorders and another cohort consisting of about 800 families affected by ASD. The researchers analyzed both copy-number variants (CNVs)individual variations in the number of copies of a particular geneand single-nucleotide variants (SNVs)DNA sequence variations affecting a single nucleotide.
They found that females diagnosed with a neurodevelopmental disorder or ASD had a greater number of harmful CNVs than did males diagnosed with the same disorder. Moreover, females diagnosed with ASD had a greater number of harmful SNVs than did males with ASD. These findings suggest that the female brain requires more extreme genetic alterations than does the male brain to produce symptoms of ASD or neurodevelopmental disorders. The results also take the focus off the X chromosome for the genetic basis of the gender bias, suggesting that the burden difference is genome wide.
"Overall, females function a lot better than males with a similar mutation affecting brain development," Jacquemont says. "Our findings may lead to the development of more sensitive, gender-specific approaches for the diagnostic screening of neurodevelopmental disorders."
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Girls require more extreme genetic mutations to develop the condition So, it is less likely they will be pushed over the diagnostic threshold About 1.8% of boys have autism compared to 0.2% of girls
By Emma Innes
PUBLISHED: 06:23 EST, 28 February 2014 | UPDATED: 09:24 EST, 28 February 2014
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Boys are more likely to have autism that girls are because they have 'less robust brains', research suggests
Researchers claim to have discovered why autism is more common in boys than girls.
A study, published in the American Journal of Human Genetics, suggests girls require more extreme genetic mutations than boys to develop the condition.
As a result, it is less likely that they will be pushed over the diagnostic threshold for autism.
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Why men are more likely to have autism: Their brains are more prone to genetic flaws, study finds
It has long been known that men have a greater risk for developing autism and other neurodevelopmental disorders, compared to women. While boys have a one in 52 chance of developing autism spectrum disorders (ASD), the risk is only one in 252 for girls, according to the U.S. Centers for Disease Control and Prevention (CDC).
Now, a new study published by the American Journal of Human Genetics reveals why so many more men are affected by these diseases.
Previously, researchers had speculated that mutations on the X chromosome may be to blame for the prevalence of ASD among men. However, study author Evan Eichler, a professor of genome sciences at the University of Washington School of Medicine, said that doesn't seem to be the case.
"Five percent of genes responsible for brain development map to the X chromosome," Eichler told FoxNews.com. "There are not enough brain development genes on the X chromosome to account for that big of a difference in terms of gender bias."
In an effort to puzzle out the gender disparity seen in autism and other disorders, Eichler and his colleague Sbastien Jacquemont, of the University Hospital of Lausanne in Switzerland, paired up to analyze DNA samples from nearly 16,000 people with neurodevelopmental disorders. They also analyzed additional samples from a separate cohort of 800 families affected by ASD.
Through their analyses, the researchers began to notice that despite the fact that more boys are affected by ASD, the serious genetic mutations responsible for these diseases were more likely to be passed to children through their mother's DNA, as opposed to from their father.
"We started to see this bias coming from mothers, who were supposed to be unaffected, that they were more likely to be transmitting mutations we thought were deleterious," Eichler said.
After analyzing the cohort of 16,000 individuals with neurodevelopmental disorders, Eichler and his colleagues also discovered that female children seemed to have a larger number of genetic mutations associated with neurodevelopmental disorders, compared to male children.
"If we divide the cohort into females and males, and look at really big mutations, do we see a difference between boys and girls in terms of frequency?" Eichler said. "The answer was, unequivocally, yes. Girls tend to have more of these than boys. Boys have fewer than females."
In analyzing the cohort of 800 families affected by ASD, the researchers also saw that girls had more major genetic deletions - and more small mutations - compared to boys.
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DNA Genotek at ESHG 2013 - Dr. Calvin Harley, Ph.D. of Telomere Diagnostics presents at ESHG 2013
Calvin Harley, Ph.D., of Telomere Diagnostics shares his clinical research work into the impact of telemere length on health and aging at the 2013 European S...
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I am Syra Mehdi, and my purpose is to provide you with the latest most interesting and fascinating research in the world of science. -Biotechnology, the comb...
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By Dennis Thompson HealthDay Reporter
TUESDAY, Feb. 25, 2014 (HealthDay News) -- U.S. Food and Drug Administration hearings opened Tuesday on a controversial fertilization technique that uses the DNA from three people -- two women and one man -- with the goal of preventing inherited genetic diseases.
The technique involves the unfertilized eggs, or "oocytes," from two females. Parts of each egg are combined to weed out inherited genetic disorders contained in one woman's DNA, and the resulting healthy egg is then fertilized using a male's sperm.
The FDA's two-day hearing is meant to provide a forum for discussing how this technique might be tested in human clinical trials.
But the discussion is expected to veer into the ethics of manipulating human genetics to produce "perfect" babies.
"The potential benefits are huge, but the potential harms are also huge," said Dr. Michelle Huckaby Lewis, a faculty member at the Johns Hopkins Berman Institute of Bioethics and the Genetics and Public Policy Center, in Washington, D.C.
The procedure could have unintended health consequences both for newborns and for future generations, as the genetic tinkering reverberates through time, Lewis said.
In addition, she said, the technique raises troubling questions of parental rights and family structure.
"When you use a technology in a new way like this, it really challenges our notions of what it means to be a parent and what it means to be a family," Lewis said.
The hearing was prompted by the work of Shoukhrat Mitalipov, an associate scientist at Oregon Health & Science University (OHSU).
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Story Created: Feb 26, 2014 at 12:27 AM ECT
Story Updated: Feb 26, 2014 at 12:27 AM ECT
INFECTIONS In addition to HPV infections discussed last week, there are other infections that can increase the risk of cancers. Hepatitis B and C viruses increases the risks of liver cancers. Human T-Cell Leukemia Virus -(HTLV-1)-Increases the risk of leukemia and lymphoma. Human Immunodeficiency virus (HIV)-increases the risk of lymphoma, and a rare cancer called Kaposi Sarcoma. Epstein Barr Virus (E.B. virus) is linked to increased risk of lymphoma. Human Herpes Virus is a risk factor for Kaposi Sarcoma Helicobacter Pylori-a is bacteria that causes stomach ulcers and is thought to increase the risk of stomach cancers and lymphomas.
ALCOHOL There are clear patterns that have emerged between alcohol consumption and certain types of cancer such as head and neck cancers, oesophageal, liver, breast and colon cancers. People who consume 50 or more grammes of alcohol per day have a two or three times greater risk of developing cancer than non drinkers. When alcohol is metabolised, it forms a compound known as Acetaldehyde which is toxic and a possible human carcinogen which damages human DNA. Alcohol also generates reactive oxygen species which damages the DNA, in addition, alcohol impairs the bodys ability to break down and absorb a variety of nutrients that may be associated with cancer risks. Alcohol also increases blood levels of oestrogen, a sex hormone linked to risk of breast cancers.
FOODS AND CHEMICALS Chemicals can be found in certain foods such as potato chips, French fries and other food products which are produced by high temperature cooking. One example is Asparagine which is an amino acid, a building block of proteins found in many vegetables and foods, such as potatoes. When heated to high temperatures, Asparagine, can form Acrylamide -a possible human carcinogen which can cause oral, pharynx, larynx, breast and ovarian cancers. Heterocyclic amines (HCA) and Polycyclic aromatic hydrocarbons (PAH) have also been found to be cancer causing. These are produced when muscle meat, including beef, pork or poultry, is cooked at very high temperature. HCA and PAH can cause mutations or changes in DNA that may increase cancer risks. Artificial sweeteners: These are substances that are used instead of sucrose (table sugar) to sweeten food and beverages. They include; saccharin, aspartame, sucralose, neotame and cyclamate. Many of these chemicals are thought to be carcinogenic as they have been found to cause cancers in animal studies. Agricultural products: Researches have shown that people exposed to certain products may have an increased risk of developing one or more types of cancer. Farmers, farm workers and family members may be exposed to substances such as pesticides, herbicides, engine exhausts, solvents, dusts, animal viruses, fertilisers, fuels and certain microbes that may increase cancer risks. Chemicals such as Formaldehyde, a colorless, flammable, strong smelling chemical used in building materials and house hold products,is also carcinogenic especially in cases of long term exposures. It is used in pressed woods, particle boards, plywoods, fibre boards, glues and adhesives, and is also found in fungicides, germicides, disinfectants and in preservatives in mortuaries. People who have certain jobs like painters, construction workers and those in chemical industries have increased risk of certain cancers especially when exposed to chemicals such as Asbestos, benzene, cadmium, nickel and vinyl chloride.
RADIATION Ionising radiation can cause cell damage that leads to cancers. X rays medically used for diagnostic investigations can increase cancer risk, even though the risk is low. Radiation therapy used to treat certain cancers can also increase the risk of some other cancers. Its not uncommon to meet a patient who requests an X-ray even when it is not necessary. The fact is that x-rays are a diagnostic tool, not a treatment, and they are not always beneficial. Unnecessary demand and frequent exposure to them may not be a wise idea. Ultra Violet (UV) radiation from the sun is another risk factor. Our UV index is generally high each time you see the weather news. These rays cause the early aging of the skin and skin changes that can lead to skin cancers, especially in caucasians, albinos and people with low melanin (skin pigmentations).
HAIR DYES More than 5,000 different chemicals are used in hair dye products, some of which are reported to be carcinogenic. Over the years, some studies have found an increased risk of bladder cancers in hairdressers and barbers. Some studies also linked the personal use of hair dyes with increased risks of certain cancers of the blood and bone marrow. However some of these studies need further research to make definitive conclusions but given the widespread use of hair dye products, even a small increase in risk may have a considerable public health impact.
SMOKING The role of smoking in the development of many forms of cancers is well documented. Each cigarette consists of over 400 carcinogenic materials that causes DNA damage and increased cancer risks as well as other diseases.
AGEING Cancer risk increases as you grow older, with most cancers occuring in people during their fifties or sixties. However many other cancers do develop before then, and there are some forms of cancers that afflict children.
FAMILY HISTORY Certain cancers develop because of changes or mutations in genes and risk factors can trigger some of these changes. Several cases of the same cancer types in a family are linked to inherited gene changes. If you think you are at risk, talk to your doctor and get checked. Contact Dr Maxwell on 3631807/7575411.
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The human genome contains approximately 20,000 protein coding genes which are responsible for the formation, development and functioning of the human body. A similar number of genes exists in the mouse genome. In this pool only some genes -- called tumor suppressors -- can initiate the production of proteins having anti-cancer properties. Polish-Australian team of researchers from the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw .and Monash University Central Clinical School in Melbourne showed that one of the genes, known as GRHL1, displays anti-cancer effects which is protective against skin cancer of non-melanoma type.
"In humans, we know more than 700 tumor suppressor genes, but only a few of them prevent the development of skin cancer. We have identified yet another tumor suppressor gene, whose damage certainly increases the risk of skin cancer, at least in a mouse model," says Dr. Tomasz Wilanowski from the Nencki Institute.
Cancer is currently one of the deadliest and most common diseases. According to statistical data from the World Health Organization, annually more than 8 million people die of cancer worldwide. Therefore understanding the causes of this disease and development of effective methods of prevention and therapy of cancer are of great social importance.
In 1998, Dr. Wilanowski identified, cloned and described a new human gene. GRHL1 (Grainyhead-like 1) proved to be a factor co-responsible for the formation of the largest human organ: the skin. This allowed the Polish-Australian research team to carry out experiments on the influence of this gene on the incidence of skin cancer.
"The tests that we conducted recently in our laboratory, leave no doubt. In the control mice, severe skin cancers developed in 7% of the population. In knockout mice, that is, in mice lacking the functional GRHL1 gene, such tumors appeared in as many as 33% of cases," says PhD student Michal Mlacki of the Nencki Institute, lead author of the paper that was just published in a well-known scientific journal PLOS ONE.
Researchers from the Nencki Institute emphasize that these numbers cannot be automatically applied to the human population. "Although mouse and human are very similar in terms of genetics and physiology, they are still different organisms. Mice are only research models of human disorders and facilitate better understanding of disease processes," says Michal Mlacki.
"Today we cannot yet unequivocally answer the question whether people with a defective GRHL1 gene will be five times more likely to develop non-melanoma skin cancer, as it happens in mice, or whether the risk of this disease will increase fourfold, or sixfold. Studies on the determination of the scale of the increased risk in human population have only just begun," notes Dr. Wilanowski.
Finding of a new tumor suppressor gene is the first step towards the development of tests to detect defective GRHL1 gene in children and adults. In the future, people aware of their genetic defect could take preventive measures to reduce the risk of skin cancer, for example, by avoiding tanning salons, suitably dressing on a sunny day or using creams effectively blocking ultraviolet radiation.
"Gene itself is only the vehicle of information. It is the encoded protein that is responsible for anti-cancer effect of the GRHL1 gene. Now that we know the functions of this protein, we would like to find a way to stimulate its activity in the human body. And this is the way not only to prevention, but also to future drugs that can be administered to patients," says Dr. Wilanowski.
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New tumor suppressor gene will facilitate detection of people susceptible to skin cancer
Dr. Anthony Komaroff/Universal Uclick
In last week's column, a reader asked whether she should be tested for genes linked to Alzheimer's disease. Today, I thought I'd give you my view on the larger question: Will studies of our genes change the practice of medicine and improve our lives?
My answer: During my career, progress in human genetics has been greater than virtually anyone imagined. However, human genetics also has turned out to be much more complicated than people imagined. As a result, we have not moved as rapidly as we had hoped in changing medical practice.
I graduated from medical school in the late 1960s. We knew what human genes were made of -- DNA -- and we were beginning to understand how genes work. We had even identified a handful of genes that were linked to specific diseases. We assumed that disease resulted from an abnormality in the structure of a gene.
If I had asked any biologist on the day I graduated, Will we ever know how many genes we have, and the exact structure of each gene? I'll bet the answer would have been: Not in my lifetime, or my children's lifetime.
They would have been wrong. Today we do know those answers. Indeed, some diseases are caused by an abnormality in the structure of genes. In fact, sometimes it is very simple: one particular change at one particular spot in just one particular gene leads to a specific disease. Sickle cell anemia is an example.
Unfortunately, with most diseases it's far from that simple. The first complexity: Most diseases are influenced by the structure of multiple genes, not just one. Examples are diabetes and high blood pressure.
The second complexity: Many diseases are explained not by an abnormal gene structure, but by whether genes are properly turned on or off. Most cancers fall into this category.
What do I mean by that? Every cell in our body has the same set of genes. Yet, a cell in our eye that sees light is different from a cell in our stomach that makes acid. Why? Because different genes are turned on in each type of cell.
Similarly, if a gene with a normal structure is not properly turned on or off, a cell can malfunction -- it can become diseased. Whether a gene is turned on properly is proving to be a more important cause of disease than we once imagined.
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ASK DOCTOR K: Progress in genetics will lead to better diagnosis
Details Published on Tuesday, 25 February 2014 16:53
Hardened plaque discovered on the teeth of 1,000 year old human skeletons has revealed not only their diets but the diseases they faced.HARDENED plaque discovered on the teeth of 1,000-year-old human skeletons has revealed the world's oldest case of gum disease.
Described as a 'microbial Pompeii', the plaque preserved bacteria and microscopic particles of food on the surfaces of teeth, effectively creating a mineral tomb for microbiomes.
And it revealed that our ancestors had gum disease that was caused by the same bacteria that plagues modern man, despite major changes in diet and hygiene.
They found that the ancient human oral microbiome already contained the basic genetic machinery for antibiotic resistance over eight centuries before the invention of antibiotics in the 1940s.
DNA testing of the tartar also showed some of the things ancient humans had been eating, such a vegetables, which do not show up in fossil records.
Gum disease is caused by a build-up of plaque on the teeth and is thought to affect over half of adults in the UK.
The teeth were taken from skeletons found at a site in Dalheim, Germany.Plaque is a sticky substance that contains bacteria and when it hardens it forms tartar.
Unlike bone, which rapidly loses much of its molecular information when buried, calculus grows slowly in the mouth and enters the soil in a much more stable state, helping it to preserve biomolecules.
Researchers from the University of York, along with Swiss and Danish colleagues, said studying plaque will be more important than teeth in discovering the lifestyles of our past ancestors.
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Plaque On 1000-Year-Old Human Teeth Could Unlock Secrets Of Medieval Diet And Disease