Category Archives: Human Genetics

[Editors note: This is one partofa two-part series examining organizations that place ideology ahead of sciencewhen opposing advances in genetics.The companion piece on NGOs that misrepresent the science about food, farming and biotechnology can be found here.]

The science ofhuman geneticstouches our lives in a wide range of ways. We have expanded our knowledge ofhow the brain works, what race is (and isnt), how we can determine guilt or innocence in crimes,and even why we may behave the way we do. For some,including certain non-government organizations, this is scary stuff. Clearly, the human genetics arena is not as volatile as on the one comprising GMOs and agriculture. But here we look at several of these groups. Some of their concerns may be legitimate (genetic privacy and false results from forensic DNA tests, for example), but there are times when theyleave science behind when expressingconcerns about frighteningbut unlikelyscenarios.

GeneWatch UK is a nonprofit advocacy group,founded in 1998 and based in Buxton, England, that opposes the use of GMOs in agriculture. The group also opposes gene patents as well as the genetic modification and cloning of animals.

GeneWatch supportsgenetic modification only whenthere is no alternative to alleviate human (or animal) suffering. The organization also presumes that genetic engineering will lead tobiological weapons. The group also has raised concernsabout the storing of genetic information in databases and has pushed forregulations prohibitingdiscrimination by employers, insurers, police or others in official positions.

GeneWatch is skeptical that gene therapy or modification could lead to the development of personalized medicine or even treat the majority of diseases. It also believes that genetic testing does a poor job of identifying cures for diseases. According to GeneWatch:

Genes are poor predictors of common complex diseases in most people and targeting a minority of genetically susceptible individuals is usually a poor health strategy. The health impacts of smoking, poor diets, poverty and pollution are not limited to individuals with bad genes and require population-based preventive strategies (such as providing better sports facilities, healthier school meals and banning fast food ads to children).

While genetic testing and the development of precision medicine has had its uncertain starts and failures, many of these initial setbacks have been due to lack of sufficient data on specific genetic markers in disease, and not on a conceptual failure of the role of genetics in disease.

ETC Group (full name: Action Group on Erosion, Technology and Concentration) was renamed in 2001 from the former Rural Advancement Foundation International (RAFI), which traces its roots to the 1930s-era National Share Croppers Fund. RAFI was an advocate for farmers rights, opposing whattermed seed monopoly laws andgenetic modification in agriculture. RAFI changed its name to ETC Group to ensure non-profit status in the United States. The Canadian group is based inWinnipeg, Manitoba.

In the 1990s, itsfocus expanded from agricultureand GMOs to include human genetic issues, such as biopiracy,human genomics and nanotechnology. The group says it wasone of the first organizations to warn of the downside of genetic engineering of crops and livestock and has since kept an eye on developments in human biotech, synthetic biology, biowarfare and industrial biotech.

On synthetic biology, for example, ETC Group has called for stricter regulations, arguing: Synthetic biologists, engaged in a kind of extreme genetic engineering, hope to construct designer organisms that perform specific tasks such as producing biofuels or other high-value compounds. The group has even issued a comic book outlining these concerns, and arguesthat there is a lack of oversight of synthetic biology.

This is an oversimplification. The actual field is nowhere near the stage of creating monsters in the lab; instead, most synthetic biology consists of sequencing and assembling existing genes and oligonucleotide sequences for experimentation. If such genetic engineering efforts do indeed mix or edit existing genomes, regulations do exist to monitor these developments, beyond the Precautionary Principle recommendations under the Convention on Biological Diversity, the 1992 United Nations treaty that covers a variety of biological issues, including thegenetics use restrictions.

The Council for Responsible Genetics, based in Cambridge, Massachusetts, was founded in 1983. The organization says it reviews scientific data and analyzes where the information can influence policy.

One of the Councils major issues is genetic privacy. It has expressed concerns about a lack of adequate regulation to protect people with a genetic propensity toward disease. To organization worries that consumer genome companies like 23andMe can use individuals genetic sequences without regulatory oversight, and that DNA samples can be obtained, bought, sold and transferred with similar impunity.

These concernshavebeen met with some opposition from scientists, who useDNA sampleswhile researching genetic links todiseases, distribution of traits among and within certain populations, and to gain insights into how genes create and maintain us. However, therehave been mistakes and abuses arising from access to DNA. 23andMe, for example, had to stop selling genetic tests that predicted risks of disease at the request of the FDA, but resumed its consumer testing service with some modifications.

The organization also wantsstricterregulation of human cloning. The organization opposes human cloning and germ cell cloning, but supports cloning for stem cell research. After a 2014 paper was published that advanced the possibilities of human and germline cloning, Gruber told USA Today:

The science is no longer theoretical. We need to start putting laws into place to identify where the line should be drawn in terms of governance of these techniques.

The organization also has published a number of what it calls gene myths, demonstrating its skepticism of the value of genetics research in a number of areas, including population genetics, the genetics of race, the role of genes in mental disorders, published claims assert that genes exist for marital infidelity and for voting behavior, and that genetic tests can accurately predict childrens success in particular sports.

These are rather simplistic claims, since while genes, for example may not predict voting behavior, they can help us understand the evolution of certain behavioral traits (aggression, attraction for authority) that may have a genetic component.

The Center for Genetics and Society, based in Berkeley, California, was originally known as the Exploratory Initiative on the New Human Genetic Technologies before it was reorganized and renamed in 2001.Itwas created with the stated goalof alerting dozens of leaders of scientific, medical, womens health, environmental, human rights, social justice and other constituencies to the need for policies addressing the new human genetic technologies.

The organization supports genetic research that can result in improvements in health. According to CGS, biotech tools and practices have the power to promote or undermine individual well-being and public health, to create private fortunes or advance the public interest, and to foster or threaten a just and fair society.

Itwants a ban on any genetic technology that would fundamentally change the nature of the human speciesin other words, anything involving alteration of the germ line. These technologies include human cloning, particularly reproductive cloning, and mitochondrial DNA replacement therapy.

Other technologies of concern include in vitro fertilization (IVF), due to pre-implantation genetic diagnosis and commercial gestational surrogacy, which the group saysis conducted with little government regulation or oversight. CGS also is concerned about the use of chimeras or hybrid organisms for research, because of the question of legal or moral standing of a human-animal chimera.

Such concerns are moral based on arguments, with possible legal repercussions, but are not necessarily grounded in science.

Andrew Porterfieldis a writer, editor and communications consultant for academic institutions, companies and non-profits in the life sciences. He is based in Camarillo, California. Follow@AMPorterfieldon Twitter.

For more background on the Genetic Literacy Project, read GLP on Wikipedia.

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4 human genetics organizations that put ideology ahead of science - Genetic Literacy Project

Scientists have long sought a strategy for curing genetic diseases, but with just a few notable exceptions have succeeded only in their dreams. Now, though, researchers in China and Texas have taken a step toward making the fantasies a reality for all inherited diseases.

Using the gene-editing tool known as CRISPR/Cas9, the researchers have successfully edited disease-causing mutations out of viable human embryos. Other Chinese groups had previously reported editing human embryos that could not develop into a baby because they carried extra chromosomes, but this is the first report involving viable embryos (SN Online: 4/8/16; SN Online: 4/23/15).

In the new work, reported March 1 in Molecular Genetics and Genomics, Jianqiao Liu of Guangzhou Medical University in China and colleagues used embryos with a normal number of chromosomes. The embryos were created using eggs and sperm left over from in vitro fertilization treatments. In theory, the embryos could develop into a baby if implanted into a womans uterus.

Researchers in Sweden and England are also conducting gene-editing experiments on viable human embryos (SN: 10/29/16, p. 15), but those groups have not yet reported results.

Human germline editing wasnt realistic until CRISPR/Cas9 and other new gene editors came along, says R. Alta Charo, a bioethicist at the University of Wisconsin Law School in Madison. Weve now gotten to the point where its possible to imagine a day when it would be safe enough to be feasible. Charo was among the experts on a National Academies of Sciences and Medicine panel that in February issued an assessment of human gene editing. Altering human embryos, eggs, sperm or the cells that produce eggs and sperm would be permissible, provided there were no other alternatives and the experiments met other strict criteria, the panel concluded (SN: 3/18/17, p. 7).

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CRISPR/Cas9 is a tool for editing genes. A guide RNA shepherds the Cas9 enzyme to a specific stretch of DNA. Cas9 then cleaves the DNA to disable or repair a gene.

Illustrations: E. Otwell

Still, technical hurdles remain before CRISPR/Cas9 can cross into widespread use in treating patients.

CRISPR/Cas9 comes in two parts: a DNA-cutting enzyme called Cas9, and a guide RNA that directs Cas9 to cut at a specified location in DNA. Guide RNAs work a little like a GPS system, says David Edgell, a molecular biologist at Western University in London, Ontario. Given precise coordinates or a truly unique address, a good GPS should take you to the right place every time.

Scientists design guide RNAs so that they will carry Cas9 to only one stretch of about 20 bases (the information-carrying subunits of DNA) out of the entire 6 billion base pairs that make up the human genetic instruction book, or genome. But most 20-base locations in the human genome arent particularly distinctive. They are like Starbucks coffee shops: There are a lot of them and they are often similar enough that a GPS might get confused about which one you want to go to, says Edgell. Similarly, guide RNAs sometimes direct Cas9 to cut alternative, or off-target, sites that are a base or two different from the intended destination. Off-target cutting is a problem because such edits might damage or change genes in unexpected ways.

Its a major issue for sure, says Bruce Korf, a geneticist at the University of Alabama at Birmingham and president of the American College of Medical Genetics and Genomics Foundation. Doctors trying to correct one genetic defect in a patient want to be sure they arent accidentally introducing another.

But CRISPR/Cas9s propensity to cut undesired sites may be exaggerated, says Alasdair MacKenzie, a molecular biologist at the University of Aberdeen in Scotland. In experiments with mice, MacKenzie and colleagues limited how much Cas9 was produced in cells and made sure the enzyme didnt stick around after it made an edit. No off-target cuts were detected in any of the mice resulting from successfully edited embryos, MacKenzie and colleagues reported in November in Neuropeptides.

Other researchers have experimented with assembling the Cas9 and guide RNAs outside of the cell and then putting the preassembled protein-RNA complex into cells. Thats the strategy the Chinese researchers took in the new human embryoediting study. No off-target cuts were detected in that study either, although only one edited embryo was closely examined.

Other researchers have been tinkering with the genetic scissors to produce high-fidelity versions of Cas9 that are far less likely to cut at off-target sites in the first place.

When a guide RNA leads Cas9 to a site that isnt a perfect match, the enzyme can latch onto DNAs phosphate backbone and stabilize itself enough to make a cut, says Benjamin Kleinstiver, a biochemist in J. Keith Joungs lab at Harvard Medical School. By tweaking Cas9, Kleinstiver and colleagues essentially eliminated the enzymes ability to hold on at off-target sites, without greatly harming its on-target cutting ability.

Regular versions of Cas9 cut between two and 25 off-target sites for seven guide RNAs the researchers tested. But the high-fidelity Cas9 worked nearly flawlessly for those guides. For instance, high-fidelity Cas9 reduced off-target cutting from 25 sites to just one for one of the guide RNAs, the researchers reported in January 2016 in Nature. That single stray snip, however, could be a problem if the technology were to be used in patients.

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Snipping the wrong bit of DNA is a potential problem for gene editing. In recent experiments, researchers modified the Cas9 enzyme in a CRISPR/Cas9 system to create a high-fidelity version that reduced off-target cutting.

Source: B. Kleinstiver et al/Nature 2016

A group led by CRISPR/Cas9 pioneer Feng Zhang of the Broad Institute of MIT and Harvard tinkered with different parts of the Cas9 enzyme. That team also produced a cutter that rarely cleaved DNA at off-target sites, the team reported last year in Science.

Another problem for gene editing has been that it is good at disabling, or knocking out, genes that are causing a problem but not at replacing genes that have gone bad. Knocking out a gene is easy because all Cas9 has to do is cut the DNA. Cells generally respond by gluing the cut ends back together. But, like pieces of a broken vase, they rarely fit perfectly again. Small flaws introduced in the regluing can cause the problem gene to produce nonfunctional proteins. Knocking out genes may help fight Huntingtons disease and other genetic disorders caused by single, rogue versions of genes.

Many genetic diseases, such as cystic fibrosis or Tay-Sachs, are caused when people inherit two mutated, nonfunctional copies of the same gene. Knocking those genes out wont help. Instead, researchers need to insert undamaged versions of the genes to restore health. Inserting a gene starts with cutting the DNA, but instead of gluing the cut ends together, cells use a matching piece of DNA as a template to repair the damage.

In the new human embryo work, Liu and colleagues, including Wei-Hua Wang of the Houston Fertility Institute in Texas, first tested this type of repair on embryos with an extra set of chromosomes. Efficiency was low; about 10 to 20 percent of embryos contained the desired edits. Researchers had previously argued that extra chromosomes could interfere with the editing process, so Lius group also made embryos with the normal two copies of each chromosome (one from the father and one from the mother). Sperm from men that have genetic diseases common in China were used to fertilize eggs. In one experiment, Lius group made 10 embryos, two of which carried a mutation in the G6PD gene. Mutations in that gene can lead to a type of anemia.

Then the team injected Cas9 protein already leashed to its guide RNA, along with a separate piece of DNA that embryos could use as a template for repairing the mutant gene. G6PD mutations were repaired in both embryos. Since both of the two embryos had the repair, the researchers say they achieved 100 percent efficiency. But one embryo was a mosaic: It carried the fix in some but not all of its cells. Another experiment to repair mutations in the HBB gene, linked to blood disorders, worked with 50 percent efficiency, but with some other technical glitches.

Scientists dont know whether editing just some cells in an embryo will be enough to cure genetic diseases. For that reason, some researchers think it may be necessary to step back from embryos to edit the precursor cells that produce eggs and sperm, says Harvard University geneticist George Church. Precursor cells can produce many copies of themselves, so some could be tested to ensure that proper edits have been made with no off-target mutations. Properly edited cells would then be coaxed into forming sperm or eggs in lab dishes. Researchers have already succeeded in making viable sperm and eggs from reprogrammed mouse stem cells (SN: 11/12/16, p. 6). Precursors of human sperm and eggs have also been grown in lab dishes (SN Online: 12/24/14), but researchers have yet to report making viable human embryos from such cells.

The technology to reliably and safely edit human germline cells will probably require several more years of development, researchers say.

Germline editing as altering embryos, eggs and sperm or their precursors is known probably wont be the first way CRISPR/Cas9 is used to tackle genetic diseases. Doctors are already planning experiments to edit genes in body cells of patients. Those experiments come with fewer ethical questions but have their own hurdles, researchers say.

We still have a few years to go, says MacKenzie, but Ive never been so hopeful as I am now of the capacity of this technology to change peoples lives.

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Gene editing of human embryos yields early results | Science News - Science News

New genetic disorder named for Children's Hospital of Philadelphia ... Science Daily Three scientists at Children's Hospital of Philadelphia who identified and studied a genetic disease have been recognized by having their names attached to the ... and more »

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New genetic disorder named for Children's Hospital of Philadelphia ... - Science Daily

Identifying genes key to human memory: Insights from genetics and cognitive neuroscience Science Daily The study is among the first to identify correlations between gene data and brain activity during memory processing, providing a new window into human memory. It is part of the nascent but growing field of 'imaging genetics,' which aims to relate ... and more »

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Identifying genes key to human memory: Insights from genetics and cognitive neuroscience - Science Daily

An international team of researchers from institutions around the world, including Baylor College of Medicine, has discovered that mutations of the OTUD6B gene result in a spectrum of physical and intellectual deficits. This is the first time that this gene, whose functions are beginning to be explored, has been linked to a human disease. The study appears in the American Journal of Human Genetics.

Our interest in this gene began when we carried out whole exome sequencing the analysis of all the protein-coding genes of one of our patients who had not received a genetic diagnosis for his condition that includes a number of intellectual and physical disabilities, said co-first author Dr. Teresa Sim, a postdoctoral associate of molecular and human genetics and a fellow in Clinical Molecular Genetics and Genomics. We identified OTUD6B, a gene that until now had not been linked to a health condition.

We identified a presumed loss-of-function mutation in the OTUD6B gene in our first patient, said co-senior author Dr. Magdalena Walkiewicz, assistant professor of molecular and human genetics at Baylor and assistant laboratory director at Baylor Genetics. We discovered that this gene seemed to be highly involved in human development; when the gene cannot fulfill its function, the individual presents with severe intellectual disability, a brain that does not develop as expected and poor muscular tone that limits the ability to walk, as well as cardiovascular problems.

Making a convincing case for OTUD6B

However, one case does not represent sufficient evidence to support the involvement of OTUD6B in the medical condition.

To make a convincing case that this gene is essential for human development we needed to find more individuals carrying mutations in OTUD6B, Walkiewicz said.

Mutations in OTUD6B are rare so the researchers had to look into the exomes all the protein-coding genes of a large number of individuals to find others carrying mutations in this gene. Walkiewicz and her colleagues first looked into their clinical exome database at Baylor Genetics labs, specifically into the data of nearly 9,000 unrelated, mostly pediatric-age individuals, many of which carrying neurologic conditions, and found an additional individual carrying genetic changes in the same gene. The clinical characteristics of this individual were strikingly similar to those of the first patient, which led the team to expand their search for more patients.

When we study very rare disorders we rely on collaborations with scientists around the world to find other families affected by mutations in one gene, said Walkiewicz.

One of the strategies that helps researchers find more cases is running the gene of interest through GeneMatcher, a web-tool developed as part of the Baylor-Hopkins Center for Mendelian Genomics for rare disease researchers. Similar to online dating websites that match couples, GeneMatcher allows researchers to find others that are interested in the same genes they are working on.

Without this type of collaborations it would be very difficult to make a convincing case. Between GeneMatcher and our database we found a total of 12 individuals carrying mutations in OTUD6B and presenting with similar clinical characteristics, Walkiewicz said.

An animal model corroborates the human findings

Animal models are one way to determine whether a change in this gene is actually causing the condition, said co-senior author Dr. Jason Heaney, assistant professor of molecular and human genetics and director of the Mouse Embryonic Stem Cell Core at Baylor. Having a similar change in an animal model gene that results in similar characteristics in a mouse can show us whether the gene is causing the condition.

Baylor is part of the International Mouse Phenotyping Consortium. Its goal is to generate a knockout model for every gene in the mouse genome, about 20,000 protein-coding genes, and determine what each gene is involved with.

In this case we learned in the animal model lacking the OTUD6B gene that the gene is highly expressed in the brain and we knew that the patients had reduced intellectual capacities. The animals had cardiovascular defects very similar to those in the patient population. The animal models allowed us to see that having this mutation of this gene causes the clinical characteristics observed in the patients. It highlights how useful animal models can be for understanding human disease, Heaney said.

Through multiple lines of evidence the researchers have established that mutations in OTUD6B can cause a range of neurological and physical conditions and highlight the role of this gene in human development.

In addition, our collaborators in Germany performed functional analysis for this gene on blood cells from patients, Walkiewicz said. Their findings suggest that the OTUD6B protein contributes to the function of proteasomes, large molecular complexes that are at the center of the cellular process that degrades proteins that are damaged or are not needed by the cell. This discovery strengthens the notion that disturbances of the proteasome can cause human disease.

There is interest in better understanding the mechanisms of the disorder at the cellular and molecular level. By understanding the processes that lead to the disease, we can then hope to develop therapies for those patients, said Walkiewicz. One of the highlights of this project is the tremendous collaboration with a number of different centers and labs and putting this tremendous effort together resulted in a publication that is very strong.

Another important contribution of this project is that we provided some answers for the families, and brought them together which offers the opportunity of mutual support, said Sim.

This article has been republished frommaterialsprovided by Baylor College of Medicine. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference

Teresa Santiago-Sim, Lindsay C. Burrage, Frdric Ebstein, Mari J. Tokita, Marcus Miller et al. and Federico Zara. Biallelic Variants in OTUD6B Cause an Intellectual Disability Syndrome Associated with Seizures and Dysmorphic Features. The American Journal of Human Genetics, 2017; DOI: 10.1016/j.ajhg.2017.03.001

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Gene Linked to Wide Range of Intellectual, Physical Disabilities - Technology Networks

Editors note: This commentary is by Steve May, who is a member of the Richmond Selectboard and a licensed independent clinical social worker. He has served previously as a national director of state Affairs for the Hemophilia Federation of America and is founder of The Forum on Genetic Equity, a national organization on genetic bias.

H.R.1313 (the Preserving Employee Wellness Programs Act) passed markup out of the House Ways and Means Committee on a party line vote with 22 Republicans voting for the bill and 17 Democrats voting against it. While the bill hasnt gotten anywhere near the attention the repeal of the Affordable Care Act has, overturning genetic privacy rules would have every bit as consequential an impact. H.R.1313 would permit genetic testing to be rolled into workplace wellness programs.

Obama era laws and regulations permitted for certain workplace wellness programs to be voluntary. The degree by which it would be voluntary going forward serves as something of an open question. There is a consensus amongst hiring managers and HR professionals that the only programs which are truly effective are the ones which target costly chronic and genetic conditions. Employers in targeting these would gain two significant pieces of information. Through enrollment and utilization they could target those who are healthy and identify those who have reason to believe they are not.

People with genetic conditions will either not be hired or hired at lower wages than they otherwise would have received as their employers and thus their insurers now know with less uncertainty future medical expense obligations.

These programs through coercive activity or incentive would create an opt-in and present little concern for those who are well. They would present their own genotype eagerly, demonstrating their own genetic wellbeing. Even a voluntary system shifts the onus onto those who for one reason or another chooses to not participate. Second, though opting out these employers would get genetic profiles with highly probable high cost diseases flagged. Far more dangerous to workers would be ones decision to not participate. While voluntary, these programs intend to compel individual participation by employers. If the cost of non-participation is high, that is a very valuable signal that the non-participating person has a damn good reason to not participate. And now they have demonstrated that they are not a team player which is really a proxy for a high likelihood of having a high probability of having a high cost genetically influenced condition. So people with genetic conditions will either not be hired or hired at lower wages than they otherwise would have received as their employers and thus their insurers now know with less uncertainty future medical expense obligations.

Following more than a decade of consultation, lobbying and advocacy, a Democratic Congress passed and a Republican president enthusiastically supported, championed and signed the Genetic Information Non-discrimination Act (GINA) in 2008. GINA is widely considered to have been the first major civil rights law of our new century; and it has successfully managed to safeguard the genetic privacy rights of every American every day for the last decade. The American Society for Human Genetics has come out against the passage of H.R.1313 because it would effectively repeal the fundamental genetic and health privacy protections in GINA and the Americans with Disabilities Act. Passage of H.R.1313 would permit workplace wellness programs to ask employees questions about genetic tests taken by themselves or their families, and to make inquiries about the medical history of employees, their spouses, their children, and other family members as employees. It is foreseeable that hiring and promotion decisions could depend on the results of genetic testing.

Under existing law, an employer may not ask a potential employee to take a genetic test as a condition of employment. That is to say they cannot pit two roughly equal applicants against one another and then consider the genetic factors and future affliction that might affect eventual employment. Supposing that you might be a carrier for BRCA-1, the genetic marker associated with breast cancer and another candidate may not, that single factor alone may be determinative in whether you get a job or a future promotion. It must be pointed out that simply being a carrier for a genetic condition does not mean that one necessarily will experience onset in most cases. In spite of that fact however, hiring managers can make employment decisions based on potential future health care costs in choosing one candidate over another.

Perhaps even more concerning is the potential for the discovery of a genetic predisposition, like Huntingtons disease. For that individual, somebody who will almost definitely contract the medical condition much later in life, (but not for several decades) the prospect of genetic profiling is downright harrowing. Huntingtons or Parkinsons will present if detected on one genetic profile, but the discovery of its existence may not affect ones health and wellbeing when it is discovered on a healthy individuals profile removed by many decades from actual onset for a given individual. In this case, the intervening event impacting ones health may be completely different, and human resource professionals, hiring managers and employers are ill-equipped to make decisions about the complex science of genomics and therefore use a disclosure as the basis to preclude one from the employment pool. Equally distressing is the idea that health insurance companies would be permitted to use genetic information and big data to inform patterns of underwriting in health insurance.

In the absence of GINA, genetic profiling could be used to determine health insurance rates. Currently, nothing precludes insurance companies from using this data in underwriting life, long-term care and disability insurance as policy makers have historically trailed badly behind this emerging technology. We dont redline neighborhoods anymore, why would we permit the formation of virtual genetic ghettos? Using factors like: race, class, gender, socio-economic status to inform patterns of underwriting in insurance products is bad public policy, why would using genetic predispositions in the form of genotyping be any better?

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Steve May: The future genetic ghetto - VTDigger - vtdigger.org

OTUD6B gene mutations cause intellectual and physical disability Science Daily "We identified a presumed loss-of-function mutation in the OTUD6B gene in our first patient," said co-senior author Dr. Magdalena Walkiewicz, assistant professor of molecular and human genetics at Baylor and assistant laboratory director at Baylor ...

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OTUD6B gene mutations cause intellectual and physical disability - Science Daily

UK Biobank announced a major research initiative with GSK and the Regeneron Genetics Center (RGC) to generate genetic sequence data from the 500,000 volunteer participants in the UK Biobank resource. The initiative will enable researchers to gain valuable insights to support advances in the development of new medicines for a wide range of serious and life threatening diseases.

Genetic evidence has revolutionised scientific discovery and drug development in recent years by providing clear links between genes and disease. Currently, an estimated 90% of potential medicines entering clinical trials fail to demonstrate the necessary efficacy and safety, and never reach patients. Many of these failures are due to an incomplete understanding of the link between the biological target of a drug and human disease. By contrast, medicines developed with human genetic evidence have had substantially higher success rates and patient care has benefited.

UK Biobank is the worlds most comprehensive health resource. It has been collecting information and samples from its 500,000 participants for the past ten years, and ensures that data provided to health researchers does not identify them. RGC and GSK have committed an initial investment to enable the sequencing of the first 50,000 samples, to be completed before the end of 2017. Sequencing of UK Biobanks samples will be carried out at the RGC, New York, one of the worlds largest human genetics sequencing centres. Sequencing of the full 500,000 samples in UK Biobank is expected to take three to five years.

Consistent with the founding principles of UK Biobank, these sequence data will be incorporated back into UK Biobanks resource following a standard exclusivity period for GSK and Regeneron (9 months for the initial phase) and made openly available to the broader scientific community. Research findings will also be submitted for publication in peer-reviewed journals.

Sir Rory Collins, UK Biobank Principal Investigator and BHF Professor of Medicine & Epidemiology at Oxford University, said: As a result of the altruism and continued support of our volunteer participants, UK Biobank has amassed an enormous amount of securely-stored health, lifestyle, medical and biological data. Genetics research is already shaping better treatments. This exciting initiative is expected to start producing novel findings rapidly during this year and will make UK Biobank even more useful for health-related research.

UK Government and charity medical research funders have invested about 200 million in UK Biobank. The costs of gene sequencing are falling, but doing it on a large scale involves highly-specialised capabilities and is expensive with an estimated cost of $150 million if all 500,000 participants are sequenced. That is why academia and industry working together is so important. The initial investment by GSK and Regeneron will be a tremendous boost to the value of the UK Biobank resource for academic and industry researchers around the world, studying many different conditions.

The RGC has previously sequenced DNA samples from more than 150,000 individuals and is now sequencing at a rate exceeding 150,000 individuals per year. The centre has successfully applied large-scale human genetics to discover new drug targets and validate existing development programmes, and has collaborated with more than 35 institutions around the world.

GSK has significant expertise in genomics and is increasingly incorporating the almost daily advances in this scientific field into its drug research programmes. A dedicated team of scientists focus on identifying new opportunities for drug discovery based on genetically-validated drug targets, working across the Companys R&D organisation, and through major external collaborations. GSKs Open Targets collaboration with the European Bioinformatics Institute, the Wellcome Trust Sanger Institute and Biogen includes an open access research platform, which makes genetic and biological data openly available to support drug discovery. Over 60% of the targets selected for new GSK drug discovery programmes in 2016 are supported by human genetic evidence.

Comment from Patrick Vallance, President, R&D at GSK:

I believe that we are in a new era of drug discovery because of a fundamental change in our understanding of human biology, driven largely by advances in human genetics. UK Biobank is one of the most important health resources available to scientists today, offering a rich source of information about health and disease.

Having been actively involved in UK Biobank as a board member since 2013, Im delighted that, through our collaboration with Regeneron, we can enrich this resource for the wider scientific community and also provide potential new opportunities for companies such as ours to develop new medicines for patients.

It demonstrates how important the UK is as a centre for innovative research. GSK is committed to ensuring that the UK continues to be an environment that fosters collaboration and supports end-to-end scientific progress, ranging from cutting-edge genomics to the rapid uptake of new approaches and medicines by the NHS, which can ultimately benefit patients.

Comment from George D Yancopoulos, MD, PhD, President and Chief Scientific Officer of Regeneron:

Our large-scale sequencing and analysis capabilities, coupled with UK Biobanks vast trove of de-identified biological and medical information, pose tremendous opportunities for clinically meaningful discoveries that can make a difference for patients. We have long-recognised that advancing the pace and clinical utility of human genetics research requires collaboration and an open exchange of data between industry, academia and public health groups, and we are pleased to expand upon our existing foundational research collaborations through this effort with the UK Biobank and GSK. For Regeneron, we believe this initiative will greatly enhance our existing efforts in gene discovery and genetics-guided drug development.

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GSK & Regeneron Announce Big Gene Sequencing Initiative - Drug Discovery & Development

Recently, Vitaliy Husar received results from a DNA screening that changed his life. It wasn't a gene that suggested a high likelihood of cancer or a shocking revelation about his family tree. It was his diet. It was all wrong.

Illustration: Angelica Alzona/Gizmodo

That was, at least, according to DNA Lifestyle Coach, a startup that offers consumers advice on diet, exercise and other aspects of daily life based on genetics alone. Husar, a 38-year-old telecom salesman, had spent most of his life eating the sort of Eastern European fare typical of his native Ukraine: Lots of meat, potatoes, salt and saturated fats. DNA Lifestyle Coach suggested his body might appreciate a more Mediterranean diet instead.

"They show you which genes are linked to what traits, and link you to the research," Husar told Gizmodo. "There is science behind it."

DNA Lifestyle Coach isn't the only company hoping to turn our genetics into a lifestyle product. In the past decade, DNA sequencing has gotten really, really cheap, positioning genetics to become the next big consumer health craze. The sales pitch a roadmap for life encoded in your very own DNA can be hard to resist. But scientists are sceptical that we've decrypted enough about the human genome to turn strings of As, Ts, Cs and Gs into useful personalised lifestyle advice.

Indeed, that lifestyle advice has a tendency to sound more like it was divined from a health-conscious oracle than from actual science. Take, for instance, DNA Lifestyle Coach's recommendation that one client "drink 750ml of cloudy apple juice everyday to lose body fat".

"Millions of people have had genotyping done, but few people have had their whole genome sequenced," Eric Topol, a geneticist at Scripps in San Diego, told Gizmodo. Most consumer DNA testing companies, like 23andMe, offer genotyping, which examines small snippets of DNA for well-studied variations. Genome sequencing, on the other hand, decodes a person's entire genetic makeup. In many cases, there just isn't enough science concerning the genes in question to accurately predict, say, whether you should steer clear of carbs.

"We need billions of people to get their genome sequenced to be able to give people information like what kind of diet to follow," Topol said.

Husar stumbled upon the Kickstarter page for DNA Lifestyle Coach after getting his DNA tested via 23andMe a few years earlier. He wondered whether there was more information to be gleaned from his results. So six months ago, he downloaded his 23andMe data and uploaded it to DNA Lifestyle Coach. Each test costs between $US60 ($78) and $US70 ($91).

"I'm always looking for some ways to learn about my health, myself, my body," said Husar, who contributed to the company's Kickstarter back in 2015.

The advice he got back was incredibly specific. According to DNA Lifestyle Coach, he needed to start taking supplements of vitamins B12, D and E. He needed more iodine in his diet, and a lot less sodium. DNA Lifestyle Coach recommended that 55 per cent of his fat consumption come from monounsaturated fats like olive oil, rather than the sunflower oil popular in Ukraine. Oh, and he needed to change his workout to focus more on endurance and less on speed and power.

He switched up his workout and his diet, and added vitamin supplements to his daily routine. The results, he found, were hard to dispute: He lost 3kg, and for the first time in memory didn't spend Kiev's long harsh winter stuck with a bad case of the winter blues.

Image: A sample of a DNA Lifestyle Coach customer's fitness recommendations provided by a customer.

For now, DNA Lifestyle Coach's "interpretation engine" only offers consumers advice on diet and exercise, but in the coming months it plans to roll out genetics-based guidance on skin care, dental care and stress management. The company wants to tell you what SPF of sunscreen to use to decrease your risk of cancer, and which beauty products to use to delay the visible effects of ageing. Its founders told Gizmodo that eventually they envision being able to offer their customers recipes for specific meals to whip up for dinner, optimised for their genetic makeup.

DNA Lifestyle Coach joins a growing list of technology companies attempting to spin DNA testing results into a must-have product. The DNA sequencing company Helix plans to launch an "app store for genetics" later this year. One of its partners is Vinome, a wine club that for $US149 ($194) a quarter sends you wine selected based on your DNA. Orig3n offers genetics-based assessments of fitness, mental health, skin, nutrition and even obviously unscientific which superpower you are most likely to have. The CEO of the health-focused Veritas Genetics told Gizmodo that the company hopes to create a "Netflix for genetics", where consumers pay for a subscription to receive updated information on their genome for the rest of their life.

"It's not going to happen overnight, but we believe that DNA will become an integrated part of everyday life," Helix co-founder Justin Kao told Gizmodo. "The same way people use data to determine which movie to see or which restaurant to eat at, people will one day use their own DNA data to help guide everyday experiences."

Few would debate that our capability to decipher information from our genetic code is getting a lot more sophisticated. Just a decade ago, a bargain-basement deal on whole genome sequencing would run you $US300,000 ($391,491). Recently, DNA sequencing company Illumina announced plans do it for just $US100 ($130) within the next decade. Every day, researchers discover new links between our health, our environment and our genetics.

But much of this research is still preliminary, and many of the studies are small. DNA Lifestyle Coach's advice to drink 750ml of cloudy apple juice for fat loss, for instance, stemmed from a study of just 68 non-smoking men. Those results, while promising, still require much larger studies to confirm. Suggesting that the same regiment might work for consumers is a little like reading the leaves at the bottom of a tea cup extracting meaning from patterns that aren't necessarily there.

Not to mention that the information our genes offer up is probabilistic, not deterministic. You may have run into this if you've done an ancestry DNA test and received results indicating that your parents are only "very likely" your parents. More often than not, many genes contribute to a specific trait like taste and how those genes all interact is a complex and poorly understood web. To complicate matters further, the expression of genes is often impacted by our behaviour and the environment. If you have a gene that raises the risk for skin cancer, but live in overcast Seattle and don't ever go outside, your chances of getting cancer are probably slimmer than someone who lives in Sydney and spends every day in the sun without slapping on some sunblock.

DNA Lifestyle Coach, though, wants to offer its customers simple, actionable advice, and so omits all this confusing grey area from its results. Instead, the recommendations are clear and specific, from how much Vitamin A to take to how many cups of coffee a day are most beneficial. It's a bit reminiscent of a long-term weather forecast spitting out predictions for sunshine or rain 30 days in advance yes, such predictions can be made, but most meteorologists will tell you they're borderline useless.

Image: A sample of a DNA Lifestyle Coach customer's diet recommendations provided by a customer.

"We use a series of algorithms which rank studies by reliability of results," the company website explains. "Studies are then analysed for their relation to real-world dietary and nutritional needs, and the user is given straightforward recommendations."

Pressed on the questionable nature of that apple juice study, DNA Lifestyle Coach's founders responded that the "data is not as strong" as the the other studies it pulls from. "But it is a harmless recommendation," the company said.

When asked whether it was possible that DNA Lifestyle Coach's claims might have any validity, Topol laughed.

One day, he said, it's likely we'll have some genomic insight into what types of diets are better suited for certain people. But, he added, it's unlikely that we will ever accurately predict the sort of granular details DNA Lifestyle Coach hopes to, like exactly what SPF of sunscreen you should be using on your skin.

"There are limits," he said.

Image: A sample of a DNA Lifestyle Coach customer's diet recommendations provided by a customer.

DNA Lifestyle Coach was founded by a chemist and a business consultant who met over an interest in the biohacker scene, a subculture focused on ideas like DIY life extension. The company that runs DNA Lifestyle Coach, Titanovo, actually started as a blog. The name is meant to invoke superhumans. "It's like the rise of the titans," said Corey McCarren, the business side of the duo, when Gizmodo met with him at a health "moonshots" conference last month.

Their first foray into genetics was a home telomere length test, which launched in 2015 with help of $US10,000 ($13,050) raised on Indiegogo. Telomeres are little bits of DNA at the end of chromosomes. Each time a cell divides, its telomeres get shorter, and so they provide some insight into our biological age. Titanovo wanted to develop an easy test to tell consumers how long or short their telomeres were. The company initially pitched the test as a way to measure both longevity and health, but eventually was forced to clarify for customers that it is not at present possible to discern biological age from telomeres alone, after receiving emails from customers panicked about their own short telomeres.

Instead, they suggest, the $US150 ($196) telomere testing kit is a way to discern information about health. One finding from their data: Vegetarians and vegans who use the service have, on average, longer telomeres. The company recommends going veg if you find your telomeres are in need of a boost. Even this, however, seems like a stretch: Data on telomere length, like genomics, is not quite ready for public consumption. For every paper that finds a potential cause of telomere shorting, there's one that finds the opposite effect.

Undaunted by the rocky rollout of its telomere testing kit, Titanovo is now pressing forward into genomics. The Kickstarter campaign for DNA Lifestyle Coach wound up raising more than $US30,000 ($39,149). The company says it now has more than 1000 customers who either pay $US215 ($281) for the full DNA testing kit along with one panel, or the $US60 ($78) to $US70 ($91) to run panels with data from services like 23andMe.

While it might seem harmless to take part in a little science-based superstition and find out whether you're more Batman or Superman, such indulgence can have serious side effects. For years, we've been sold on DNA as the answer to almost everything. Decode the human genome, and decode the "mysteries of the human spirit". This gives companies like DNA Lifestyle Coach dangerous authority. If your DNA testing results say you're prone to obesity, why spend time exercising and eating right when your health seems beyond your control?

Joshua Knowles, a Stanford Cardiologist who studies applied genetics, told Gizmodo that he recently had a patient who was unwilling to try a certain class of drug based on their genotyping, even though they had a high risk of heart disease that might be drastically reduced by use of those medications.

"We're doing a poor job of educating patients on risk-benefit analysis," Knowles said. "In some cases, when it comes to genetics, we're placing a lot of weight on some things that have very small overall effects."

In 2008, an European Journal of Human Geneticsarticle argued for better regulatory control of direct-to-consumer genetic testing, asking whether in the end, tests ran the risk of being little better than horoscopes that told people information they were already predisposed to believe.

It was these kinds of concerns that moved the US Food and Drug Administration to crack down on 23andMe in 2013, ordering the company to cease providing analyses of people's risk factors for disease until the tests' accuracy could be validated. The company now provides assessments on a small fraction of 254 diseases and conditions it once scanned for it still processes the same information, but is restricted in what it can tell consumers. Where it once reported "health risks" alongside specific tips and guidance on how to reduce them, it now reports on your "carrier status", framing the results in terms of whether you might pass down a specific genetic variant to your offspring rather that whether you might develop the condition yourself.

Companies like DNA Lifestyle Coach have moved in to offer the sort of tips 23andMe no longer can.

"We have much too many companies doing nutrigenomics and other unproven things like that," said Topol. "That can give consumer genomics a really bad name. That's unfortunate."

Kao, of Helix, said that educating consumers on what these results really mean alongside actionable information will be the industry's greatest challenge and what distinguishes it from just another pseudoscientific health fad.

"It's typically been very hard to interpret DNA information," Kao said. "DNA is most valuable with context, rather than as the only piece of the puzzle."

The industry, he argues, is young, but will get more accurate the more consumers use DNA-testing products. "Just as Netflix improves the more you rate shows you watch, so would many DNA-based products," he said.

Husar told Gizmodo that he got blood work done to confirm what he could about his DNA Lifestyle Coach results. The tests indeed confirmed that he was low on vitamins B12, D and E, as DNA Lifestyle Coach had suggested. Of course, Hussar still can't be sure his genes are responsible. It could be that he's simply not eating enough meat or cheese. Still, the blood work was enough to convince Husar that DNA Lifestyle Coach's analysis was worth taking seriously. And, for the most part, the results felt right it made sense that a boost of vitamin B12 might counteract the emotional toll of winter, and that cutting out potatoes and saturated fats might be beneficial.

The tests's fitness results though, he did find a tad shocking.

"I was really surprised to learn that I'm not fast or powerful, but I have a high endurance," he said. "I can do Iron Man. This is what my genetics say. I'm trying to change my workout to see if that's true."

Husar may never be sure whether the advice divined from his genetics was really helpful. He can only hope it doesn't hurt.

Originally published on Gizmodo Australia.

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The Next Pseudoscience Health Craze Is All About Genetics - Lifehacker Australia

CBS , WTSP 6:26 AM. CDT March 21, 2017

A bill from a North Carolinarepresentative would allow companies to ask employees for genetic information. William Thomas Cain/Getty Images (Photo: William Thomas Cain, 2006 Getty Images)

Your genetic profile can reveal whether you have a disease or a predisposition to problems like cancer. So there is concern over a bill that would let companies request genetic testing, and effectively charge employees more for health insurance if they refuse.

The bill aims to clarify rules for workplace wellness programs. Employers would be able to offer discounts of up to 30 percent to those who participate. For the average family of four, that could be a difference of more than $1,500 a year.

But critics of this new bill say theres no telling how companies could use that information in the future. To them, its a choice between losing privacy or losing what could be thousands of dollars in savings.

Joselin Linder told correspondent Tony Dokoupil that, most of the time, she doesnt mind discussing the genetic illness that runs through her family attacking a vein in the liver.

So my grandmother passed it to two sons and watched two sons die of this gene, she said.

But she wouldnt want a boss to know the details of her family tree.

Dokoupila asked, How do you think you would feel if an employer said, We want to see your genetic test or were going to charge you 30% more for health insurance?

I think it would feel like a penalty, she replied.

What Linder calls a penalty, North Carolina congresswoman Virginia Foxx sees as motivation. She introduced a bill that would allow companies to offer insurance premium discounts to workers who undergo genetic testing as part of a workplace wellness program.

If they dont participate in the wellness program, their premium is going to be the same as everyone else, Foxx said.

With the exception of the people who participate in the program, said Dokoupil.

Well, its an incentive to participate in the program, Foxx replied.

Nancy Cox, president of the American Society of Human Genetics, countered, Its hard to imagine a good reason for wanting this information.

In a letter to Congress, her organization (and dozens of others) said the bill would impose draconian penalties on employees.

Federal law bans companies from using genetic information to hire, fire or discriminate. But critics say a simple blood or saliva test could eventually reveal so much about a persons health and abilities that the urge to peek might be irresistible.

There are possibilities for misusing genetic information that make it very important for this information to be private, Cox said.

When asked about the opposition to her bill, Rep. Foxx said, We are totally surprised.

She points to the benefits of companies engaging in workers health: It will save people money, and it also will help them achieve a better quality of life.

Most large companies offerwellness programs, which are supposed to encourage healthy living, prevent disease, and lower health costs.

But Joselin Linder doesnt think shed ever join one if it meant handing over her genetic information. I think all of us deserve our privacy, Linder said, and I think all of us deserve healthcare.

The Kaiser Family Foundation reports theres little evidence so far that wellness programs actually improve workers health.

Foxxs bill passed a House committee this month, and she is is optimistic about its chances of becoming law.

But with opposition mounting, it could be a tough sell in the Senate.

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Should companies be allowed to demand your genetic test results? - THV11.com