Category Archives: Genetics

Genetics

A new way of predicting which kids will succeed in school: Look at their genes – NBC News

This article about the polygenic score was produced in partnership with The Hechinger Report, a nonprofit, independent news organization focused on inequality and innovation in education. This is part 3 of the series Gifted Educations Race Problem.

Many factors boost a child's chance of success in school like having wealthy parents who can afford tutors. But recent research has raised another possibility one that is discomforting to many the idea that scientists might someday be able to spot the genetic markers associated with academic performance.

To do this, researchers are turning to a relatively new genetic approach called the polygenic score, which assesses a persons likelihood for a specific future based on a combination of genetic variables. Its a research technique that some scientists are using to assess obesity or cancer risk, for instance. Now, researchers are exploring this approach in non-medical contexts, like academic or athletic success.

The scientists studying genetic markers in education are trying to untangle how nature and nurture together explain school performance. In principle, genetic screening might enable teachers to tailor their approach to groups of students. Educators might then more effectively instruct kids together in one classroom, rather than separating students into accelerated and low-level courses, which can deprive Black and brown children and children from low-income families of academic opportunities.

But some researchers fear this gene screening work could be misapplied and used to further racist or eugenic thinking, even though race is a social, not a genetic, classification. Theres an ugly history of proponents of eugenics, who believe in reshaping humanity by breeding superior traits and removing inferior traits, justifying their thinking with genetics. And there are debunked racist theories that have endeavored to falsely connect race and intelligence.

For now, the science is almost entirely based on data collected from people with European ancestry, which limits the conclusions that can be drawn from it, so researchers feel that theyve at least temporarily sidestepped the issue.

But that doesnt mean they arent worried about it and about the other ways this research could exacerbate inequities in education. Screening is expensive, for instance, increasing the odds that privileged students will qualify for extra enrichment or support before their less privileged peers.

Indeed, the idea of predicting students academic performance based on their genes comes with such a raft of ethical questions and unknowns that scientists in the field are urging caution. Polygenic scores are a potentially useful new scientific tool. At the same time, there are clear reasons to be concerned, Stanford University social scientist Ben Domingue said. Were going to have the capacity, with a vial of spit, to be able to predict all these different things.

Scientists and ethicists are also concerned about commercializing this work while the research is still evolving. Already, several companies sell reports to consumers that incorporate polygenic scores for health or various physical characteristics despite the fact that the scores are not perfect forecasters of a persons future.

Researchers in the field want to see more critical discussion of how their work could be applied in educational settings. If we dont pay attention now, systems will be created, constructed around us, responding to our genetic difference, said Sophie von Stumm, a psychologist at the University of York, in the United Kingdom, who studies genetics and education. Its high time to have this discussion. Honestly, were late to the party.

Related: College graduation may be partly determined by your genes, genome study of siblings finds

The polygenic score that could help predict academic performance aims to assess genetic markers related to educational attainment. In other words, it combines hundreds of common genetic variants that are linked to the number of years a person stays in school. In 2016, this score could explain about 5 percent of the variation in the level of education completed.

In 2018, researchers studied data from more than a million people across countries and found they could strengthen the polygenic score to explain 11 percent of the variation in educational attainment. That value puts the score on par with factors like a mothers level of education attainment, which explains 15 percent of variation, and household income, which explains about 7 percent.

There are genes that affect educational attainment that is for certain now, said Aysu Okbay, an economist at Vrije Universiteit in the Netherlands who contributed to the 2016 and 2018 studies.

The scores ability to explain variation in years of schooling could improve with more data. Rough estimates indicate about 80 percent of the variation in educational attainment comes from environmental factors the rest is genetic. With enough data, some scientists believe, the polygenic score could get close to explaining 20 percent of the difference in peoples level of education.

If so, the score would be an incredibly powerful single factor for making predictions about an individuals academic future even though the combined environmental variables still eclipse the role of genes. Its really not a puny predictor at this point, Domingue said.

In February, Domingue and his colleagues found that the polygenic score could help identify which groups of high schoolers had been placed into advanced math classes. The score could also point to students most likely to stick with advanced math courses across all four years of high school.

But polygenic scores also come laced with caveats. So many, in fact, that Okbay and her colleagues published a massive list of public FAQs including how the study was designed and whether the research could lead to stigmatization of people with certain genes to help readers interpret their research.

For more of NBC News' in-depth reporting, download the NBC News app

Paige Harden, a clinical psychologist at the University of Texas at Austin and a co-author on the math study likens the polygenic score to a credit score. Neither the polygenic nor the credit score can really forecast what will happen to a particular person. Instead, they provide a rough sense of how people with that score will, on average, fare. The score is better at gauging a groups overall performance than an individuals performance.

Harden and others acknowledge that its still a mystery how the genetic variants behind the score contribute to how far a person gets in school. We dont know what the mechanisms are, Okbay said. We dont know whether its causal or not.

Some research suggests the genes associated with education are related to the nervous system and the brain, raising the possibility that theyre connected to cognitive functions things like strong memory, creativity and perseverance that serve people well in school.

But the relationship could be nuanced. Domingue pointed out that there could be genetic factors that make a person more likely to be a supportive parent, which, in turn, would correlate to better school performance in their children. Because the child and parent share DNA, the polygenic score could capture gene variants in the child that explain educational performance but actually reflect the parents behavior.

There is also an enormous shortcoming in the datasets used for this research: Virtually all are built with DNA from people of European ancestry. Although there are biobanks in the works in Asia and Africa that could address this omission, for the time being, the scores are essentially only applicable to people of European descent. Youre basically developing a tool thats only useful for one segment of the population, Harden said.

Related: Gifted classes may not help talented students move ahead faster

Given all of these limitations, most scientists believe it would be unlikely, and inappropriate, for educators to use polygenic scores to determine student placement in specific classes or schools. Will someone be mad enough to track or stream on the basis of genetic predispositions? von Stumm said. Fortunately, I think were far from that.

There could be other ways of using this genetic information. Once genetic variants are better understood and enough data is in hand, for example, it might be possible to identify children with a predisposition to learning disabilities and intervene early. In May, von Stumm and her colleagues published a paper exploring whether a toddlers polygenic score for educational attainment could identify children at risk for language or literacy delays later in life. The conclusion: Were not there yet.

Critics caution that there is too much to establish ethically and scientifically before we confront those scenarios. Someday well understand the genetic contribution to educational success or to life success but it will be our grandchildren who understand it. It wont be us, bioethicist Arthur Caplan at NYU Langone Health said.

And even if we understood this information, its not clear how to best use the scores in schools. Last year, Stanfords Domingue and two colleagues wrote about a hypothetical case study: What happens when a parent tries to use genetic data, like a polygenic score, to make the case that their child deserves additional classroom support?

I dont know that I have good answers to that, he said. But the scenario hints at another serious concern: inequality. Not everyone will be able to afford genetic screening, even when there are meaningful scores for people across ancestries.

Still, researchers are already using the polygenic score to explore long-standing conundrums like why children with very similar advantages follow different trajectories in life.

We are all subject to a big genetic lottery that corresponds to an environmental lottery, von Stumm said. She added that research into the links between genetics and academic attainment could push people to examine fairness in meritocratic societies, given that some people may carry genetic strengths that give them a slight but significant academic advantage, that, in turn, improves other aspects of their lives.

Measuring a persons genetic advantage (or disadvantage) also allows scientists to control for it in their studies. That is, they can better study factors that society can change, such as spending on special programs, compulsory education and school interventions, without having their results biased by a sample of students who are genetically advantaged or disadvantaged.

And researchers can use the polygenic score to assess whether a school has failed students with high potential or if an intervention helped retain children who were otherwise likely to drop out. In the math paper published in February, Domingue, Harden, and their colleagues found that some schools better supported high school students with low polygenic scores than others, ensuring those kids stayed in school.

Harden hopes to see the science applied in ways that emphasize social justice and provide resources to programs that need them: Thats how I think we should be using the polygenic scores if we use them at all.

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A new way of predicting which kids will succeed in school: Look at their genes - NBC News

Genetics

Genetic Variant for EFIH in Thoroughbreds Found The Horse – TheHorse.com

Researchers at the University of California, Davis, School of Veterinary Medicine have identified a genetic cause for the fatal condition equine familial isolated hypoparathyroidism (EFIH) in Thoroughbreds, marking the first genetic variant for hypoparathyroidism identified in any domestic animal species. Additionally, this is the first widely available genetic test for Thoroughbreds.

The study, led by Carrie Finno, DVM, PhD, Dipl. ACVIM, and Gary Magdesian, DVM, CVA, Dipl. ACVIM, ACVECC, ACVCP, wasreportedin the journalPLoS Genetics.Genetic testingcan now be performed at theUC Davis Veterinary Genetics Laboratoryto identify horses with the variant and avoid mating carriers that could produce affected foals.

For Thoroughbred owners and breeders, the loss of a foal has tremendous economic and emotional impacts, said first author Victor Rivas, who conducted the project as part of his undergraduate training in Finnos laboratory. It is important to promote safe and strategic breeding habits by actively breeding horses genetically screened not only for EFIH but for other diseases that may impact quality of life.

Foals affected with EFIH suffer from low blood calcium concentrations, resulting in involuntary muscle contractions, muscle stiffness that leads to a stiff gait and can progress to an inability to stand, seizures, fevers, and an abnormally fast pulse. Parathyroid hormone is typically produced to increase calcium levels in the body, but in these foals concentrations are low or inappropriately normal (i.e., they should be high due to the low calcium). Affected foals die or are euthanized due to poor prognosis. Necropsy results reveal underdeveloped or absent parathyroid glands.

Previously termed idiopathic hypocalcemia, EFIH has been observed in Thoroughbred foals up to 35 days of age. Disease onset and progression are likely determined by the amount of calcium in the diet early in life. This can vary based on dam milk calcium concentration and the amount of milk ingested.

In the current study, the researchers determined an autosomal recessive mode of inheritance and performed whole genome sequencing of two affected foals. A mutation in therap guanine nucleotide exchange factor 5(RAPGEF5) gene was present in two copies (homozygous) in both foals. They further analyzed the variant in a frog developmental model and demonstrated loss of function of the RAPGEF5 protein leading to aberrant development. Based on these data, the researchers hypothesize thatRAPGEF5might play a role in the derivation of the parathyroid gland during development.

Researchers have not identified the variant in individuals from 12 other breeds. The allele frequency for theRAPGEF5variant in an expanded set of 82 randomly selected, unaffected Thoroughbreds was 0.018. An unbiased allele frequency study has not been performed, so the allele frequency in the larger Thoroughbred population is currently unknown.

The next steps are to assess the allele frequency in a large population of randomly selected Thoroughbreds, said Finno. Additionally, we have discussed collaborating with Dr. Nathan Slovis at Hagyard Equine Medical Institute in Kentucky to test for the variant in cases of sudden death in Thoroughbred foals.

The clinical presentation of EFIH is similar to human familial hypoparathyroidism. Because theRAPGEF5gene is highly conserved across species, it is a potential new candidate gene for primary hypoparathyroidism in humans, the researchers said.

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Genetic Variant for EFIH in Thoroughbreds Found The Horse - TheHorse.com

Genetics

Bionano Genomics’ Saphyr System Shown to be Indispensable for the Analysis of Certain Genetic Disease Causing Variants – GlobeNewswire

SAN DIEGO, Oct. 15, 2020 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) announced that a study led by scientists and clinicians from the Institute for Human Genetics at the UCSF School of Medicine and the Department of Pediatrics at the University of Colorado School of Medicine and published in bioRxiv used Bionanos proprietary genome imaging technology to identify novel disease causing variants in patients with three different genetic diseases and in a diverse control dataset of 154 individuals. The study found that Bionano's Saphyr System was able to comprehensively analyze complex genome structures called segmental duplications and helped identify several novel structural variations associated with each disease causing locus increasing the understanding of these diseases.

Segmental duplications are large segments of repetitive sequences tens to hundreds of thousands of base pairs in size. Short-read and long-read sequencing technologies cannot span these large segments of the genome. Only Bionanos optical mapping technology can image single molecules that are so long that they span the segmental duplications. These repetitive sequences can interact with each other when sperm or eggs are created and their rearrangement can cause severe genetic disease. Some of the most common of such diseases are microdeletions at 7q11.23, also known as Williams-Beuren syndrome (WBS), 15q13.3 microdeletion syndrome, 16p12.2 microdeletion syndrome and 22q11.2 deletion syndrome, also known as DiGeorge syndrome.

This study, published in bioRxiv, provides a population-level analysis of segmental duplications in 154 people and in patients with WBS, 15q13.3, and 16p12.2 microdeletion syndromes. Several novel SVs were detected for each locus, and the exact disease causing rearrangement was determined with much higher accuracy than was formerly possible without Saphyr. As previously announced, a recent publication in the journal Nature published on July 22, 2020 also discussed the unique contribution of Bionanos optical mapping technology to understanding the genetic causes of DiGeorge syndrome.

Erik Holmlin, Ph.D., CEO of Bionano Genomics commented, The microdeletion and microduplication syndromes are common genetic disorders, yet the exact genomic structures that cause them have been difficult or impossible to characterize with current sequencing-based methods. Even though microdeletion syndromes are commonly represented by hallmark features, in many cases a wide variability in clinical features is observed. Being able to understand and measure the subtle structural differences in microdeletions among different patients could allow for better clinical or therapeutic management. An increasing number of studies have relied on Bionanos Saphyr system to characterize disease-causing structural variants that could not be correctly analyzed with other molecular techniques. We will continue to make our technology available to researchers everywhere who want to greatly expand the capabilities of their genomic analysis.

The publication is available at https://www.biorxiv.org/content/10.1101/2020.04.30.071449v1.full

About Bionano GenomicsBionano is a genome analysis company providing tools and services based on its Saphyr system to scientists and clinicians conducting genetic research and patient testing, and providing diagnostic testing for those with autism spectrum disorder (ASD) and other neurodevelopmental disabilities through its Lineagen business. Bionanos Saphyr system is a platform for ultra-sensitive and ultra-specific structural variation detection that enables researchers and clinicians to accelerate the search for new diagnostics and therapeutic targets and to streamline the study of changes in chromosomes, which is known as cytogenetics. The Saphyr system is comprised of an instrument, chip consumables, reagents and a suite of data analysis tools, and genome analysis services to provide access to data generated by the Saphyr system for researchers who prefer not to adopt the Saphyr system in their labs. Lineagen has been providing genetic testing services to families and their healthcare providers for over nine years and has performed over 65,000 tests for those with neurodevelopmental concerns. For more information, visitwww.bionanogenomics.com or http://www.lineagen.com.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the contribution of Bionanos technology to the analysis or understandings of microdeletion syndromes and future development of better clinical or therapeutic management for such diseases; the effectiveness and utility of Bionanos technology in clinical settings; Saphyrs capabilities in comparison to other genome analysis technologies; the benefits of Bionanos optical mapping technology and its ability to facilitate genomic analysis in future studies; and Bionanos strategic plans. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive products; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; the loss of key members of management and our commercial team; and the risks and uncertainties associated withour business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2019 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 (617) 430-7577arr@lifesciadvisors.com

Media Contact:Darren Opland, PhDLifeSci Communications+1 (617) 733-7668darren@lifescicomms.com

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Bionano Genomics' Saphyr System Shown to be Indispensable for the Analysis of Certain Genetic Disease Causing Variants - GlobeNewswire

Genetics

An evolutionary jolt helped cattle to spread across Africa. Now genetics must make them more productive – The Conversation Africa

African cattle breeds are astonishingly diverse, and often quite beautiful. They range from the dark-red Ankole of southern Uganda, with their massive heat-dissipating horns, to the Boran which thrive in the dusty plains of northern Kenya, to Ethiopias sturdy Mursi cattle, with their prominent shoulder humps and hanging dewlaps. The Kuri that graze on the grasses of Lake Chad are adept swimmers; the Red Fulani can trudge vast distances along the margins of the Sahara; and the famously disease-resistant Sheko inhabit tsetse fly-infested forests of southwest Ethiopia.

All billion or so cattle today descend from ancient aurochs, an extinct species of wild cattle that once inhabited large swaths of Eurasia. These cattle were domesticated on at least two distinct occasions approximately 10,000 years ago during the Neolithic era: once in south Asia leading to the zebu or humped cattle and the other in the Middle East leading to the taurine or humpless cattle.

In Africa, the oldest archaeological evidence of domestic cattle dates back to between 6000 and 5000 BC in western Egypt. These taurine cattle, initially confined to the Saharan-Sahelian belt, eventually reached isolated pockets of land in West and East Africa.

Africas cattle today have adapted to the climate, forage conditions, diseases and pests prevalent in their habitat. The individuals best adapted to their environments were more likely to survive and reproduce. They were also more favoured by people. Over time this led to different breeds and species.

Today there are an estimated 800 million livestock keepers across the continent. Cattle provide nutritious, calorie-dense food, much-needed income, and nitrogen-rich manure for replenishing soils. There are few regions of Africa where cattle do not play a central role, both economically and culturally.

But it was not always this way. My colleagues and I from the International Livestock Research Institute (ILRI) recently published a paper detailing how African cattle acquired their adaptive capacities.

Sifting through the DNA of 16 indigenous African breeds, we discovered a thousand-year-old event in which the worlds two main subspecies of cattle namely taurine and zebus mixed. This allowed African cattle after spending thousands of years confined to certain regions in Africa to diversify and spread across the continent.

Our findings help to explain how African cattle spread throughout the continent. But since they were selected and bred for resilience, African cattle never became as productive, in terms of meat or milk, as breeds in more temperate climates. Our hope is that, by studying the history hidden in indigenous cattle genomes, we can help guide efforts to breed for productivity without losing the breeds native resilience and sustainability.

Our new genome sequencing work revealed that, about a thousand years ago, pastoralist herders in the Horn of Africa began breeding the Asian zebu cattle with local taurine breeds.

The zebu offered traits that allowed cattle to survive in hot, dry climates. The taurine traits provided cattle with the ability to endure humid climates, where vector-borne diseases that affect cattle, like trypanosomiasis (or sleeping sickness) are common.

This event, which we dubbed an evolutionary jolt, allowed African cattle after spending thousands of years confined to a shifting patchwork of sub-regions in Africa to spread across the continent and flourish into the breeds we see today.

But this resilience came at a cost. African cattle are often not as productive in terms of growth rates, meat or milk as their European and American cousins. Canadian Holsteins, for example, can deliver 30 litres of milk per day, several times what most African breeds are capable of. Traditional Ethiopian Boran, for example, produced only four to six litres of milk per day.

Today scientists at ILRI, in partnership with governmental institutions in Tanzania and Ethiopia, are again trying to deliver an evolutionary jolt to Africas cattle. This time, however, they want to speed up the evolutionary clock by identifying genetic markers that signal both adaptability and productivity. Screening embryos for these markers could help scientists replicate in the lab the slow work of evolution by favouring the traits that most benefit farmers.

Earlier efforts to improve cattle productivity on the continent focused on importing cattle breeds from elsewhere, without adequately recognising African breeds unique resilience. Nearly, all these attempts have failed or resulted in crossbreeds with both adaptability and productivity diluted.

This time, we are focusing on sustainable productivityproductivity that builds on rather than disregards the resilience of indigenous African breeds.

But while we have new tools and shortcuts which enables scientists to analyse vast swaths of genetic data and decide which breeds could work well together, there are some lessons we should still draw from the first evolutionary jolt.

The first is that we shouldnt be overly concerned about crossbreeding. Because of a sense of national pride and wanting to conserve indigenous African cattle breeds, there is at times a tendency on the part of some to treat them as iconic, untouchable manuscripts.

This ignores the long tradition of crossbreeding practised by African livestock farmers and pastoralists they were (and still are) constantly mixing and matching breeds to select the animals best suited to their needs.

Another lesson is that, as scientists experiment and cross-breed, it is vitally important to remember that the local breeds have adaptations not all of them immediately obvious (a tolerance for episodic drought, for example) that have enabled their success. It is important that we do not lose those adaptive traits in the randomness of crossbreeding.

This will take innovative crossbreeding programs that incorporate scientists, government ministries, private partners and farmers to ensure the conservation of genetic information across the long life cycle of cattle generations.

And finally, its essential to include the practical, accumulated experience of pastoralists in these processes.

David Aronson, Senior Communications Advisor with ILRI, contributed to the writing of this article

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An evolutionary jolt helped cattle to spread across Africa. Now genetics must make them more productive - The Conversation Africa

Genetics

Proving The Value Of Preventive Genomics – Bio-IT World

By Deborah Borfitz

October 15, 2020| The Bio-IT World Conference & Expo closed out with a plenary keynote presentation on preventive genomics by Robert Green, M.D., professor of medicine at Harvard Medical School and a physician-scientist who directs the G2P Research Program at Brigham and Womens Hospital and the Broad Institute. Data-sharing difficulties were a recurring theme at this years conference but, as the COVID-19 Host Genetics Initiative has demonstrated, it is possible to combine genomic data to rapidly explore markers of disease, he says. But far more daily deaths are caused by cancer and cardiovascular diseasenot the pandemic virusand 59 of the causal genes are already known and actionable.

Genomic information is rarely incorporated into clinical care partly because labs, not care providers, are doing most of the testing and doctors are unclear if the benefits outweigh the costs and risks, says Green. The clinical value of DNA sequencing is also unproven, although its the central feature of personalized medicine programs that have been popping up around the country.

Green presented lessons learned from the MedSeq, exploring the impacts of incorporating genomic sequencing into everyday medicine for people with and without a suspected genetic cardiac disease, and BabySeq, testing methods for integrating sequencing into the care of newborns. Both are randomized trials funded by the National Institutes of Health.

MedSeq involved primary care physicians taking comprehensive family histories on participants with or without the addition of one-page genomic reports and following their outcomes. Reports from preventive genomic testing focused on defined, disease-specific variants with the highest clinical actionability, says Green, as distinct from indication-based testing looking at a wider universe of variants known or suspected of being pathogenic.

Notably, Green says, neither doctors nor patients experienced test-related anxietyeven when a monogenetic risk variant was discovered. In 100 individuals, 20% were found to carry a dominant mutation for a monogenetic condition. In fact, among the top four genetic mutations, sequencing often discovered ongoing disease that the healthcare system had missed.

Participating doctors, after only six hours of training, did not make any errors in communicating the results, adds Green. Healthcare spending six months post-disclosure was higher but not extraordinarily more. Two years later, 22% had been reclassified (e.g., variant of uncertain significance now likely benign or likely pathogenic variant now pathogenic).

In the smaller BabySeq Project, 11% of participants were identified as having monogenetic disease risk, Green says. As with MedSeq, a substantial number with genetic mutations already had phenotypic evidence of disease previously missed by their healthcare providers.

BabySeq additionally revealed no difference in bonding or vulnerability, says Green. Catastrophic distress is not an obstacle [to sequencing], as has often been suggested. The falling cost of genomic sequencing and interpretation should further improve the benefit-to-cost ratio.

Exactly how often does sequencing reveal something important? Herere the stats from Green: 91% of the time for recessive mutations, 80% for atypical responses to medications, 15% for dominant mutation, and 50% for elevated polygenic risk specific to at least one condition such as diabetes or cancer.

Polarizing Topic

The Mass General Brigham Biobank, which looked for the 59 genes linked to disease, has identified such mutations in over 350 of the roughly 36,000 people it has sequenced. In 75% if those cases, the mutations were linked to either cardiovascular disease or cancer and the individuals had no idea they were carrying mutations, says Green.

A significant number did not even want to know of their risk, he adds. A similarly high number met National Comprehensive Cancer Center criteria for genetic testing but had never before been tested.

The Preventive Genomics Clinic at Brigham and Womens Hospital, staffed by genetics experts and counselors, offers individuals a menu of testing options (whole genome sequencing as well as smaller panels) and also gives patients the option of being seen via telemedicine. The heart-touching stories shared on its website include a man nudged by discovered mutations to finally get a colonoscopy, revealing two cancerous lesions that were subsequently extracted, and another with worsening heart disease who learned the underlying cause was Fabry diseasea rare but treatable condition.

Genomics is a notoriously polarizing subject, Green says. The challenge in convincing the skeptics is that genomics crosses multiple therapeutic domains and testing needs to be repeated over individuals lifetime.

The exceptionalism of genomics is sometimes misplaced, he later adds, referring to the disproportionate amount of fear about misuse of genetic information relative to psychological or infectious disease data. Its perfectly possible for large groups to share genomic data that is not identifiable. Its not full-proof, but its [technically] feasible.

Federal genetic privacy laws prevent genetics-based discrimination by employers and health insurers, Green says. In July, Florida became the first state in the nation to enact a DNA privacy law that also prohibits life, disability and long-term care insurance companies from using genetic tests for coverage purposes.

Editors Note: Even if you missed the start of the event, Bio-IT World Conference & Expo virtualis still live. Register nowfor on-demand presentations.

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Proving The Value Of Preventive Genomics - Bio-IT World

Genetics

The 23andMe Genetic Kit Is an Insanely Cool Gift You May Just Want to Give Yourself – It’s on Sale For Prime Day! – Yahoo News

Amazon Prime Day is here, and have you seen these deals? They're bigger and better than ever, and we can't say we mind all that much. For two days only, you can score everything from fitness deals to beauty buys and kitchen gadgets. But, we'd be remiss if we didn't talk about the fact that it's October (seriously, how?) and gift-giving season is almost here. If you've got someone in your life who could use a cool present, consider this 23andMe Health + Ancestry Service ($99, originally $199).

This genetic-testing kit is beloved by millions, and will give you a unique and in depth look into your genetics. You can save $100 if you buy it today, which is major. Whether you want to check some people off your gifting list or are curious for yourself, now's the time to buy this insanely cool kit.

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The 23andMe Genetic Kit Is an Insanely Cool Gift You May Just Want to Give Yourself - It's on Sale For Prime Day! - Yahoo News

Genetics

Found: genes that sway the course of the coronavirus – Science Magazine

A study of some of the sickest COVID-19 patients, such as those placed on ventilators, has identified gene variants that put people at greater risk of severe disease.

By Jocelyn KaiserOct. 13, 2020 , 1:25 PM

Sciences COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

Its one of the pandemics puzzles: Most people infected by SARS-CoV-2 never feel sick, whereas others develop serious symptoms or even end up in an intensive care unit clinging to life. Age and preexisting conditions, such as obesity, account for much of the disparity. But geneticists have raced to see whether a persons DNA also explains why some get hit hard by the coronavirus, and they have uncovered tantalizing leads.

Now, a U.K. group studying more than 2200 COVID-19 patients has pinned down common gene variants that are linked to the most severe cases of the disease, and that point to existing drugs that could be repurposed to help. Its really exciting. Each one provides a potential target for treatment, says genetic epidemiologist Priya Duggal of Johns Hopkins University.

In a standard approach to finding genes that influence a condition, geneticists scan the DNA of large numbers of people for millions of marker sequences, looking for associations between specific markers and cases of the disease. In June, one such genomewide association study in The New England Journal of Medicine (NEJM) found two hits linked to respiratory failure in 1600 Italian and Spanish COVID-19 patients: a marker within the ABO gene, which determines a persons blood type, and a stretch of chromosome 3 that holds a half-dozen genes. Those two links have also emerged in other groups data, including some from the DNA testing company 23andMe.

The new study confirmed the chromosome 3 regions involvement. And because 74% of its patients were so sick that they needed invasive ventilation, it had the statistical strength to reveal other markers, elsewhere in the genome, linked to severe COVID-19. One find is a gene called IFNAR2 that codes for a cell receptor for interferon, a powerful molecular messenger that rallies the immune defenses when a virus invades a cell. A variant of IFNAR2 found in one in four Europeans raised the risk of severe COVID-19 by 30%. Baillie says the IFNAR2 hit is entirely complementary to a finding reported in Science last month: very rare mutations that disable IFNAR2 and seven other interferon genes may explain about 4% of severeCOVID-19 cases. Both studies raise hopes for ongoing trials of interferons as a COVID-19 treatment.

A more surprising hit from the U.K. study points to OAS genes, which code for proteins that activate an enzyme that breaks down viral RNA. A change in one of those genes might impair this activation, allowing the virus to flourish. The U.K. data suggest there is a variant as common and influential on COVID-19 as the interferon genetic risk factor.

Other genes identified by Baillies team could ramp up the inflammatory responses to lung damage triggered by SARS-CoV-2, reactions that can be lethal to some patients. One, DPP9, codes for an enzyme known to be involved in lung disease; another, TYK2, encodes a signaling protein involved in inflammation. Drugs that target those two genes proteins are already in useinhibitors of DPP9s enzyme for diabetes and baricitinib, which blocks TYK2s product, for arthritis. Baricitinib is in early clinical testing for COVID-19, and the new data could push it up the priority list, Baillie says.

The chromosome 3 region still stands out as the most powerful genetic actor: A single copy of the disease-associated variant more than doubles an infected persons odds of developing severe COVID-19. Evolutionary biologists reported last month in Nature that this suspicious region actually came from Neanderthals, through interbreeding with our species tens of thousands of years ago. It is now found in about 16% of Europeans and 50% of South Asians.

But the specific chromosome 3 gene or genes at play remain elusive. By analyzing gene activity data from normal lung tissue of people with and without the variant, the U.K. team homed in on CCR2, a gene that encodes a receptor for cytokine proteins that play a role in inflammation. But other data discussed at last weeks meeting point to SLC6Z20, which codes for a protein that interacts with the main cell receptor used by SARS-CoV-2 to enter cells. I dont think anyone at this point has a clear understanding of what are the underlying genes for the chromosome 3 link, says Andrea Ganna of the University of Helsinki, who co-leads the COVID-19 Host Genetics Initiative.

The U.K. genetics study did not confirm that the ABO variants affect the odds of severe disease. Some studies looking directly at blood type, not genetic markers, have reported that type O blood protects against COVID-19, whereas A blood makes a person more vulnerable. It may be that blood type influences whether a person gets infected, but not how sick they get, says Stanford University geneticist Manuel Rivas. In any case, O blood offers at best modest protection. There are a lot of people with O blood that have died of the disease. It doesnt really help you, says geneticist Andre Franke of the Christian-Albrecht University of Kiel, a coleader of the NEJM study.

Researchers expect to pin down more COVID-19 risk genesalready, after folding in the U.K. data plumbed by Baillies team, the COVID-19 Host Genetics Initiative has found another hit, a gene called FOXP4 implicated in lung cancer. And in a new medRxiv preprint posted last week, the company Ancestry.com reports that a gene previously connected to the effects of the flu may also boost COVID-19 susceptibility only in men, who are more likely to die of the disease than women.

Geneticists have had little luck so far identifying gene variants that explain why COVID-19 has hit Black people in the United States and United Kingdom particularly hard. The chromosome 3 variant is absent in most people of African ancestry. Researchers suspect that socioeconomic factors and preexisting conditions may better explain the increased risks. But several projects, including Baillies, are recruiting more people of non-European backgrounds to bolster their power to find COVID-19 gene links. And in an abstract for an online talk later this month at the American Society of Human Genetics annual meeting, the company Regeneron reports it has found a genome region that may raise the risk of severe disease mainly in people of African ancestry.

Even as more genetic risk factors are identified, their overall effect on infected people will be modest compared with other COVID-19 factors, Duggal says. But studies like the U.K. teams could help reveal the underlying biology of the disease and inspire better treatments. I dont think genetics will lead us out of this. I think genetics may give us new opportunities, Duggal says.

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Found: genes that sway the course of the coronavirus - Science Magazine

Genetics

Genetics of Height and Risk of Atrial Fibrillation: A Mendelian Randomization Study – DocWire News

Background

Observational studies have identified height as a strong risk factor for atrial fibrillation, but this finding may be limited by residual confounding. We aimed to examine genetic variation in height within the Mendelian randomization (MR) framework to determine whether height has a causal effect on risk of atrial fibrillation.

In summary-level analyses, MR was performed using summary statistics from genome-wide association studies of height (GIANT/UK Biobank; 693,529 individuals) and atrial fibrillation (AFGen; 65,446 cases and 522,744 controls), finding that each 1-SD increase in genetically predicted height increased the odds of atrial fibrillation (odds ratio [OR] 1.34; 95% CI 1.29 to 1.40; p = 5 10-42). This result remained consistent in sensitivity analyses with MR methods that make different assumptions about the presence of pleiotropy, and when accounting for the effects of traditional cardiovascular risk factors on atrial fibrillation. Individual-level phenome-wide association studies of height and a height genetic risk score were performed among 6,567 European-ancestry participants of the Penn Medicine Biobank (median age at enrollment 63 years, interquartile range 55-72; 38% female; recruitment 2008-2015), confirming prior observational associations between height and atrial fibrillation. Individual-level MR confirmed that each 1-SD increase in height increased the odds of atrial fibrillation, including adjustment for clinical and echocardiographic confounders (OR 1.89; 95% CI 1.50 to 2.40; p = 0.007). The main limitations of this study include potential bias from pleiotropic effects of genetic variants, and lack of generalizability of individual-level findings to non-European populations.

In this study, we observed evidence that height is likely a positive causal risk factor for atrial fibrillation. Further study is needed to determine whether risk prediction tools including height or anthropometric risk factors can be used to improve screening and primary prevention of atrial fibrillation, and whether biological pathways involved in height may offer new targets for treatment of atrial fibrillation.

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Genetics of Height and Risk of Atrial Fibrillation: A Mendelian Randomization Study - DocWire News

Genetics

Trumps Lifelong Obsession With His Superior DNA Is Being Put to the Test – New York Magazine

After returning to the White House from the hospital on October 5, Trump waved from the balcony. Photo: Win McNamee/Getty Images, Nicholas Kamm/AFP via Getty Images, Erin Scott/Reuters,

Last month, appearing at a rally in Minnesota, President Trump praised the superior genetic stock of his supporters in the state. You have good genes, you know that, right? Trump observed. You have good genes. A lot of its about the genes, isnt it, dont you believe? The racehorse theory. You think were so different? You have good genes in Minnesota.

The comment received some attention as fresh evidence of a decades-long streak of racism, which it certainly is. (There is obviously a reason the lineage of the heavily Nordic state drew his attention.) But Trumps observations on genetics are not only an expression of racism. It is also one of his deepest obsessions and the explanation for the bizarre passivity that has characterized his response to the coronavirus pandemic from the outset and that has led him to his likely political, if not corporeal, demise.

The classic American millionaire myth, from Carnegie to Warren Buffett, has an origin story, employing at least elements of truth, built on hard work. The hero rose at dawn and sweated and strove on his rise to greatness. And yet, despite having spent decades carefully polishing his place in the lineage of aspirational wealth, Trump has few well-known stories of pounding the pavement or poring over real-estate listings. Its instincts, not marketing studies, he wrote in The Art of the Deal, the original manifesto of his personality cult.

Instinct is something you are born with or not. In 1988, Oprah Winfrey asked Trump if all of the people reading Art of the Deal hoping to find some answer that will satisfy their own desire for success could take away inspiration and lessons. The American prosperity gospel has a hackneyed response to this question: Yes, with relentless effort and perhaps some luck, anybody can get rich in America. Even though he was peddling a book marketed to advance precisely such a fantasy, Trump could not bring himself to supply the familiar answer. You have to be born lucky in the sense that you have to have the right genes, he explained. You have to have a certain gene.

Trump brings up his belief in genes over and over. I have a certain gene, he told CNN in 2010. Im a gene believer. Hey, when you connect two racehorses, you usually end up with a fast horse. And I really was you know, I had a a good gene pool from the standpoint of that. Addressing a rally in Mississippi in 2016, he instructed the crowd, I have Ivy League education, smart guy, good genes. I have great genes and all that stuff, which Im a believer in. (In the annals of Mississippi politics, Trumps highlighting his Ivy League pedigree was probably more novel than his emphasis on genetic purity.)

The presidents idea of a fixed genetic elite and its necessary underclass counterpart would seem to undercut any moral basis for his own privilege. (The best moral case for letting rich people keep their money is that they worked hard to earn it. So if Trumps wealth is entirely the product of winning the genetic lottery, why not tax it away and redistribute the proceeds to his less fortunate inferiors?) It also stands in stark contrast to the American credo of progress.

What Hath God Wrought?, Daniel Walker Howes history of early-19th-century America, emphasizes a belief among the Founders, and especially the progressive Yankee faction, in improvement. This concept constituted both an individual and a collective responsibility, involving both the cultivation of personal faculties and the development of national resources. Just as people could and must develop their own talents through study and disciplined labor, they could enhance the potential of the country by building schoolhouses, canals, lighthouses, and universities.

It was a creed embraced by such disparate figures as John Quincy Adams, Abraham Lincoln, and Frederick Douglass. Their political rivals were southern planters who distrusted centralized government, which might threaten their immutable place atop the hierarchy. The planters defined success not as hard work but as liberation from hard work, the burden of which would fall on the people they had enslaved.

Trump has not necessarily absorbed antebellum southern thought. But he has internalized the idea of success as genetically coded and impervious to effort. The Trump success formula is 100 percent inspiration, zero percent perspiration. He has repeatedly cited his MIT-professor uncle as his own scientific credential. Trump said at the Centers for Disease Control and Prevention that he impressed his hosts with his innate grasp of public health: I really get it Every one of these doctors said, How do you know so much about this? Maybe I have a natural ability, he said, as if he were literally born understanding the workings of a virus that did not exist until 2019. NBC reported that Trump waved off the need to rigorously prepare for his debate on the grounds that debating isnt something you have to practice. His biographer Michael DAntonio once explained that Trump disdains exercise and gorges on burgers and junk food because he really believes in genetic gifts. He wants to assume that he can do something that others cant do simply because of who he is.

That is not an ideal mentality for the person youd want to be in charge of well, anything. But especially not a pandemic that requires careful study and flexibility of mind to follow a quickly mutating scientific understanding and the perseverance to encourage and adhere to disciplined hygienic rituals. Everything to him is about who you are, not what you do. Trump did not need to learn about the pandemic because he is smart. He did not need to protect himself from it because he is strong.

Trump not only lacks the patience for a laborious public-health regimen; the entire concept of it runs against his genetic fatalism. The very possibility a disease could fell blond bermensch Donald Trump almost surely never occurred to him. The president is neither a rationalist nor a religious believer. The closest proxy in his mind to a divine force is genes: invisible, all-powerful, mapping out our destinies. Were he capable of introspection, he might look upon his stricken body and dying presidency and question his false god.

*This article appears in the October 12, 2020, issue ofNew York Magazine. Subscribe Now!

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Trumps Lifelong Obsession With His Superior DNA Is Being Put to the Test - New York Magazine

Genetics

Nurse advises Rotary of the benefits of genetic testing – El Dorado News-Times

The El Dorado Rotary Club hosted Tammy McKamie, a genetic certified nurse at the Christus St. Michael Health System in Texarkana, on Monday at their regular meeting, where she spoke about the health benefits of genetic testing.

McKamie, who has worked as a medical professional for nearly 40 years, is the only credentialed genetic certified nurse in Texas, and also serves patients from Arkansas. On Monday, she discussed her specialization in genetics and the role ones genes may play in determining whether they develop cancer during their lives.

While 90% of those who develop cancer do so because of environmental and lifestyle factors, such as smoking or being exposed to carcinogenic chemicals, McKamie said some people are at a heightened risk due to genetic factors.

Almost every person is born with 23 pairs of chromosomes, half of which are inherited from their biological mother and the other half of which are inherited from their biological father.

On each one of these chromosomes, there are thousands of genes. If I add up all the genes in this DNA, were going to have about 20,000 genes, and each one of those has a purpose, McKamie said.

Some of those genes purposes are to protect the individual from developing cancer, she said, a medical breakthrough that was discovered in 1994 during research for the Human Genome Project.

God gave us genes to protect us from cancer, McKamie said. We have two of each gene that theyve discovered so far. One gene may protect you from multiple cancers, so if ones defective, you may be at risk for multiple cancers.

Rotarian Art Noyes asked whether genetic predisposition to cancer may have been related to actress Angelina Jolies decision to undergo a double mastectomy (breast removal) several years ago.

Yes, Angelinas mother had ovarian cancer, so she had this genetic testing years ago, McKamie said. She did the genetic testing and she had a genetic mutation in one of these genes. Angelina had never had cancer, but she had the genetic predisposition toward it.

In Jolies case, McKamie said, there was likely a mutation of the BRCA 1 or 2 gene, which can heighten ones susceptibility to several types of cancers, including breast cancer, ovarian cancer, prostate cancer, colorectal cancer and other types.

For those who opt not to undergo preventative surgeries, like Jolies mastectomy, knowing of any genetic defects can still help medical professionals that care for them, since they will be aware of their increased risk level. Those who do have a genetic predisposition to some types of cancer should undergo earlier and more frequent screenings so that any cancer that does develop can be treated sooner, McKamie said.

If you started out with this defect, we would not wait til 40 (years old) to do a mammogram we would start much earlier, she said. Everybody knows that if you detect cancer early, youre more likely to survive it.

McKamie said a defect in the BRCA 1 or 2 gene can heighten a womans risk of developing breast cancer significantly. For someone without a gene defect, the risk at 40 years old is about 0.5%; at 50 years old, about 2%; and at 70 years old, about 7%. For a woman who does carry a hereditary risk, the likelihood that they will develop breast cancer by age 40 increases to 10 to 20%, depending on which BRCA gene the defect is in; by age 50, the risk is 33 to 50%, and by 70 the risk is 58-87%, McKamie said. For men, the risk of breast cancer increases from 1% for the general population to 7% for those with a genetic defect.

People take it for granted that everythings working but if you knew that one of these was defective and you were at a higher risk for cancer, you might be more healthy, more conscious, McKamie said.

At Christus St. Michael, McKamie offers consultations for those who would like to undergo genetic testing to determine whether they might be at a heightened risk for developing cancer. First, she will take a detailed family medical history and explain to her patient how ones genes might increase their risk for cancer. Following that, she will draw one tube of blood from the patient and send it to a laboratory, with a typical turnaround time of two to three weeks, she said.

This testing is now even evolved to the point to where if you have cancer, the physicians will use it to determine the best type of drug to use to treat you, McKamie said. I get a lot of consults from our cancer physicians and oncologists because they need to know what type of drug to use to treat this person.

McKamie noted that Medicare pays 100% for this sort of genetic testing, and most other medical insurance companies follow their lead; additionally, should any out-of-pocket costs emerge once a patients sample reaches the testing lab, a representative from the lab will call the patient to ensure they still want the testing done.

Before a patient comes to Texarkana for a screening, McKamie will screen them over the phone to ensure they will qualify for coverage for the genetic testing, she said. Those who are interested in a consult can contact her at 903-614-2654 or [emailprotected]

[Cancer diagnostics and treatment] just really evolved, and it continues to evolve, McKamie said. This is the way of the future now.

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Nurse advises Rotary of the benefits of genetic testing - El Dorado News-Times