Category Archives: Human Genetics

Baylor College of Medicine has received more than $1 million from the National Institutes of Health to engage researchers from diverse backgrounds, including those from underrepresented groups, in utilizing the All of Us Research Programs data resources to advance precision medicine.

The All of Us Research Program is a historic effort to collect data from 1 million or more people living in the United States to support a wide range of scientific discoveries. The goal of the program is to advance research that may lead to better health for all. Diversity is one of the core values of the program, which seeks to include participants from different races, ethnicities, age groups and regions of the country. The Baylor program aims to ensure researchers using All of Us data in their studies also reflect such diversity.

As part of the effort to engage researchers from diverse backgrounds, including those from underrepresented groups, in using All of Us data, Baylor will host All of Us Evenings with Genetics seminars, modeled after the Evenings with Genetics seminars hosted by the Department of Molecular and Human Genetics, at universities across the country. The seminar series will introduce the All of Us Research Program to biomedical researchers and students from diverse backgrounds, including those from underrepresented groups, and show them how to use the data in a variety of fields, including medicine, psychology, nutrition and education.

The All of Us Evenings with Genetics program will engage students who may not have considered research as a career, said Dr. Debra Murray, co-director of the Office of Community Engagement and Diversity, assistant professor in the Department of Molecular and Human Genetics and co-investigator of the Baylor program. We hope to inspire more students to use the All of Us data to work with faculty and engage in research earlier in their academic careers.

Baylor also will host an annual conference for faculty from diverse backgrounds, including those from underrepresented groups, to establish a framework of collaboration and training using the All of Us data platform. The conference will provide long-term support to researchers and enhance the productivity of current postdoctoral trainees and early career faculty members. Conference attendees will develop multidisciplinary research projects with a foundation in the All of Us Research Program. As part of the summit, participants will be able to apply for seed awards and external pilot awards to fund additional collaborations and projects. These projects can serve as stepping stones to manuscripts and grant proposals.

This program embraces the diversity of participants of the All of Us Research Program by fostering the same diversity among the scientists who will lead us in the discoveries on this enormous dataset, said Dr. Brendan Lee, professor and chair of the Department of Molecular and Human Genetics, Robert and Janice McNair Endowed Chair in Molecular and Human Genetics at Baylor and principal investigator of the award.

Susan Fernbach, co-director of the Office of Community Engagement and Diversity and assistant professor in the Department of Molecular and Human Genetics, and Laura Rosales, administrator in the Department of Molecular and Human Genetics, are co-investigators of the program at Baylor.

Our community engagement partners provide crucial support to help deliver on the promise of All of Us, said Dr. Josh Denny, CEO of the All of Us Research Program. Through their continued commitment to the program, they fortify our network of trusted community organizations, provide a vital sounding board to shape our activities and direction, lend their expertise to overcome communities distrust of research, motivate diverse communities to enroll and remain engaged with our program and support diverse researchers doing research in All of Us.

This work is supported under NIH funding award OT2 OD031932. All of Us is a service mark of the U.S. Department of Health and Human Services.

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NIH award supports diverse researchers in All of Us Research Program - Baylor College of Medicine News

Now that early abortion is essentially banned and criminalized in Texas, with other states soon to debate similar legislation, its important to reflect on one of the key issues raised by this new law: When does human life begin? Here is a background primer on human prenatal development.

Understanding the biology is more important than ever, because the new Texas lawis even more draconian than it appears to be at first blush, if thats even possible. It bans abortion at 6 weeks, but this cutoff is actually 4 weeks after conception when the fetus is 1/25th of an inch. Counting gestation from the last menstrual period is archaic, perhaps a holdover from the days when most obstetricians were male. And as anyone who has ever suspected she is pregnant knows, that reasoning is absurdly wrong. The morning-after pill is not a two-weeks-later pill. Nonetheless and unfortunately, much of the media have spread the meaningless 6-week factoid.

Im the author of several college textbooks, on human genetics, human anatomy and physiology, and intro biology. Being a biologist, a textbook author, and a mother, Ive thought a great deal about the question of when a human life begins. So here are my selections of times at which a biologist might argue a human organism is alive. Ill save my opinion for the end.

My answer? #14.

The ability of a fetus to survive outside of a womans body sets a practical, if fluid, technological limit on defining when a sustainable human life begins.

Having an active genome, tissue layers, a notochord, a beating heart none of these matter if the organism cannot survive where humans survive, untethered and breathing oxygen.

Technology has taken us to the ends of the prenatal spectrum, yet not provided too much for the middle, other than fetal surgeries for a handful of conditions. We can collect and select gametes, and even do the same for very early embryos, allowing those without specific diseases to continue development. At the other end, the gestational age at which a premature infant can survive hasnt crept younger by much over the years.

So until an artificial uterusbecomes a practical reality, technology defines, for me, when a human life begins: at viability outside a womans body.

[Note: This article is adapted from a previous piece I posted on my website]

Ricki Lewis has a PhD in genetics and is a science writer and author of several human genetics books.She is an adjunct professor for the Alden March Bioethics Institute at Albany Medical College.Follow her at herwebsiteor Twitter@rickilewis

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Viewpoint: 'The fetus is 1/25th of an inch' Texas abortion ban bungles the science on when human life begins, contends biologist and professor -...

Scientists have also studied the nighttime rituals of another autism model: zebrafish (Danio rerio). Gene-editing techniques enable scientists to create zebrafish with autism-linked mutations, and then they can easily assess how the mutations effect behavior. We can take our fish larvae at 5 days old they have this complex range of behaviors we can easily pipette them into the wells of a 96-well plate, and then track different aspects of their locomotor activity, Hoffman says. The design offers the high throughput and easy replicability of a cell culture study, with the ability to gauge effects on animal behavior.

As a postdoctoral researcher, Hoffman tracked the behavior of 5-day-old zebrafish larvae lacking the autism-linked gene CNTNAP2 and found that they are hyperactive at night. The fish also have fewer-than-usual inhibitory neurons, which dampen neural activity, in the forebrain, replicating findings in mice lacking the same gene and adding heft to the relevance of the fish as an autism model.

Zebrafish are a useful tool for screening potential drugs for autism because chemical compounds can be added directly to the water the fish swim in. In their CNTNAP2 study, published in 2016, Hoffman and her colleagues tested the effects of 14 drugs on the larvae and showed that certain forms of the hormone estrogen can reverse the larvaes hyperactive behavior.

The animals are small and relatively inexpensive, so the team can use them to study the effects of many autism-linked genes in parallel. Hoffmans team is looking at brain activity, movement and sleep-wake cycles across multiple lines of zebrafish with mutations in the fish equivalents of 10 autism-linked genes, including CHD8, CNTNAP2, DYRK1A, GRIN2B and SCN2A. The researchers aim to identify shared characteristics across strains and to identify drugs that could reverse alterations in their behavior.

The CNTNAP2 zebrafish developed in Hoffmans lab are slated to appear on a list of validated zebrafish models curated by the Simons Foundation Autism Research Initiative (SFARI). (Spectrum is an editorially independent publication funded by SFARI.) The goal of that list is to make zebrafish research more reliable by steering researchers toward models that pass a test of genetic quality, says SFARI senior scientist Brigitta Gundersen.

Its all a matter of matching your question to the advantages and disadvantages of your model system. Ethan Scott

Zebrafish larvae have another advantage: They are transparent for the first several days of life. As a result, researchers can see the larvaes internal organs, including the gut, enabling them to visualize the effects of autism mutations on gut function, which is often disrupted in autism. In the larvae, researchers can observe the rhythmic movements of the gut muscles, and food moving through the digestive system. Things play out right in front of you, says Julia Dallman, associate professor of biology at the University of Miami in Coral Gables, Florida.

In studies published in 2019 and 2020, Dallmans team showed that the gut muscles contract, and food moves through the gut, unusually slowly in zebrafish with mutations in SYNGAP1 or SHANK3. In people, mutations in these genes are linked to both autism and gastrointestinal distress, including constipation and acid reflux. When we initially set out to look at gut function in these models, my expectation was that [alterations] would be subtle, Dallman says. Its not subtle at all. Her teams studies suggest that slightly different mechanisms underlie gut problems in the two fish strains, so treatment of constipation in autism may not be one size fits all. Dallman plans to test the effects of drugs on both gut function and behavior in the fish, to aid in the search for autism medications that dont worsen constipation, she says.

The transparency of zebrafish larvae also puts early brain development on display. Using specialized microscopes, researchers can visualize the activity of individual neurons and, because the fish are small, simultaneously track the activity of every neuron in the brain. Youre just observing the brain in an intact, alert, behaving, perceiving animal, says Ethan Scott, who studies sensory processing in zebrafish at the University of Queensland in Brisbane, Australia.

Zebrafish have a more similar brain structure to humans than do invertebrate models, Scott says. And although the fish lack a cerebral cortex, the structure at the surface of the human brain, they are useful for studying circuits in other parts of the brain. Its all a matter of matching your question to the advantages and disadvantages of your model system, Scott says.

Scott is using zebrafish larvae with mutations in autism-linked genes to investigate alterations in sensory processing in autism. He and his colleagues are monitoring their brain activity in response to images shown on a computer screen, and to sounds of varying loudness. In a 2020 study, his team showed that zebrafish lacking FMR1, the gene mutated in fragile X syndrome, are hypersensitive to sound. And in four regions of the brain, their neurons react to sound with more frequent or stronger bursts of activity than those in typical fish. The work may help explain sensory hypersensitivity in autism, Scott says.

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What studying worms, flies and fish says about autism - Spectrum

(Precision Vaccinations)

Severe COVID-19 patients tend to have one thing in common: insufficient or defective proteins that help regulate the immune system, known as type I interferons (IFNs), stated researchers with Rockefeller University.

Jean-Laurent Casanova, M.D., Ph.D., previously demonstrated that at least 10% of severe cases could be chalked up to either a genetic condition that cripples IFN production or misguided antibodies that attack those crucial proteins.

Two new studies published in Science Immunology on August 19, 2021, explain how another 10% of severe cases are linked to IFN.

These autoantibodies are found even in uninfected individuals, which suggests that they are a cause, rather than an effect, of severe COVID-19.

We can neatly explain much of severe COVID-19 as a net defect in type I IFN, Casanova stated in a press release.

To an extent never seen for any other acute infectious disease, these four studies collectively provide a molecular and immunological explanation for about 20 percent of critical cases.

The new papers highlight additional IFN-related defects unique to severe and fatal COVID-19 cases.

In the first study, Casanova and colleagues found that 1 to 2% of men under the age of 60 who experience severe COVID-19 have deleterious mutations in TLR7, a gene within the X chromosome involved in the production of type I IFN.

In the second study, the scientists demonstrated that confused antibodies were attacking type I IFNs instead of the virus account for a more significant number of severe cases than previously thought 20% of people who died from COVID-19 had high levels of autoantibodies that specifically target and destroy IFNs.

While they are in only about 0.5% of people under age 60, that number rises to 4% at age 70 and up to 7% by age 85.

These findings, resulting from the collaboration of the COVID Human Genetic Effort, a global international consortium co-led by Casanova, have immediate clinical implications.

First, it is quick and easy to test for auto-Abs against type I IFNs in patients infected with SARS-CoV-2. Screening for these antibodies is even possible in the general population before infection.

Second, patients with auto-Abs against type I IFN should be vaccinated against COVID-19 as a priority.

Third, live attenuated vaccines, including YFV-17D and vaccines using the YFV-17D backbone against SARS-CoV-2, should not be given to patients with auto-Abs.

Fourth, these patients appeared healthy before SARS-CoV-2 infection, but they should also be carefully followed for other viral illnesses, as exemplified by adverse reactions to YFV-17D.

Fifth, in cases of SARS-CoV-2 infection in unvaccinated individuals with auto-Abs against type I IFNs, the patients should be hospitalized for prompt management.

Early treatment with monoclonal antibodies can be administered in patients without symptoms of severe COVID-19 pneumonia, and IFN- can be administered in the absence of both pneumonia and auto-Abs against IFN-. Rescue treatment by plasma exchange is another therapeutic option in patients who already have pneumonia.

Sixth, blood products, especially plasma, should be screened for anti-IFN auto-Abs, and any products containing such antibodies should be excluded from donation. And plasma from donors convalescing from COVID-19 should be tested for such auto-Abs.

Seventh, given the documented innocuity and potential efficacy of a single injection, early therapy with IFN- may be considered for the contacts of contagious subjects or during the first week after infection, even in the absence of, or before the documentation of auto-Abs against type I IFNs, in elderly patients, who have a higher risk of critical pneumonia and auto-Abs against IFN-2 and IFN-, but not IFN-.

Another possibility would be the administration of monoclonal antibodies that can neutralize SARS-CoV-2.

Finally, it will be essential to decipher the mechanism underlying the development of these auto-Abs, which may differ in patients over and under 65 years of age.

Overall, our findings show that auto-Abs neutralizing concentrations of type I IFN lower than previously reported but still higher than physiological concentrations typical in the elderly population.

Notes: The COVID Human Genetic Effort is an international consortium aiming to discover the human genetic and immunological bases of the various clinical forms of SARS-CoV-2 infection.

The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the US NIH, and others. These researchers did not disclose relevant industry conflicts of interest.

PrecisionVaccinations publishes fact-checked research-based vaccine news.

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Seeking the Common Thread in Severe COVID-19 - Precision Vaccinations

Two-day event featured 10% growth in registrations and a wide array of expert stakeholders

INDIANAPOLIS, Sept. 9, 2021 /PRNewswire/ -- hc1, the leader in critical insight, analytics, and solutions for precision health, announced today the successful completion of its 2nd annual Precision Health Virtual Summit. Registrations for this year's event grew by 10%, evidencing a growing interest in the innovations and collaborations ushering in a new era of precision health.

(PRNewsfoto/hc1)

The second Precision Health Virtual Summit saw a 10% increase in registrations, showcasing interest in precision health.

The two-day event held in partnership with Becker's Healthcare featured leading experts including keynote presentations from Katherine Capps, president of Health2 Resources and co-founder and executive director of GTMRx (Get the Medications Right) Institute, and David Nash, MD, MBA, founding dean emeritus of Jefferson College of Population Health at Thomas Jefferson University.

In "Precision Health and Population Health: Friends or Foes," Nash discussed how two of healthcare's priority initiatives can work in tandem to achieve cost, access and clinical outcomes goals. Nash explained how eliminating waste in population health is a driver for precision health and ties into addressing cost and access concerns in delivering individualized care for all patients.

"It's amazing how much is changing and how quickly it is changing. Precision medicine harnessing the human genome and being able to deliver precision, personalized careit's a kissing cousin of population health; it's a subset; it's a pillar. One thing is clear: they are not on a collision course. Quite frankly, they are incredibly complementary," Nash said.

"The field of precision health is moving at light speedthe fastest in history," Jeffrey Kuhlman, MD, General Manager, Healthcare Analytics Solution, AdventHealth, told "Precision Health and Genomics: Unlocking Individuality" session moderator Mackenzie Bean, Writer/Reporter, Becker's Hospital Review. "Think about where we were in 1985 with personal computers and IT. Well, that's actually where we are today with omics and with precision health. Not just the next 25 years we're gonna see those truly amazing changes, but even within the next few years we're gonna see light speed changes. What's needed for that is we've got to develop the clinical decision support tools that allow physicians to easily access what's presented to them, in an easy to understand way, in their workflow, that's actionable that more importantly puts patients at the center of the program."

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In her presentation, "The Future of Precision Health," Capps discussed how personalized medicine and gene therapies are laying the groundwork for better care today and in the future. After providing a real-life account of the medication struggles of a patient with multiple complex conditions, she provided an overview of a new solution called Comprehensive Medication Management (CMM)a method that differs from traditional medication therapy management (MTM) and takes a systematic, integrated and collaborative approach to medications built on an understanding of how genetics influence efficacy through pharmacogenomics.

"The ultimate goal is precision preventative medicine. We believe at the institute that we can move from precise to personalized medicine through the expansion of CMM in the delivery setting through application of knowledge, access to clinical pharmacists, leveraging pharmacogenomics testing. It'll reduce burnout, increase physician, patient satisfaction. It'll lead to better outcomes at a lower cost and it'll ensure that we achieve the quadruple aim," Capps said.

Brad Bostic, Founder, chairman and CEO of hc1, opened the virtual summit with an address that focused on the challenges of healthcare's current one-size-fits-all care delivery model and how data silos create barriers to holistically addressing the needs of individual patients. He also discussed how high-impact technology partnerships are changing this dynamic through a new class of solutions called Precision Health Insight Networks (PHINS).

"I really found it an energizing, exciting opportunity to bring together people from all different parts of the healthcare value chain to talk about how we can solve this challenge of one size fits all trial-and-error care and move to more of a model that's focused on the end outcome of the patient and bringing the most precise possible approach to healthcare," Bostic noted in his closing remarks. "Today we've got about 30% of all healthcare dollars being wasted. In the future, we really need to fix that, and together we can do it. We also see about 128,000 people per year in the U.S. dying from taking medications as prescribed, and with new precision medicine techniques, with better precision approaches to managing health across populations, we can do much, much better and eliminate those unnecessary dollars and unnecessary deaths."

Sponsors of the Precision Health Virtual Summit include AWS, Snowflake and leader sponsor Quest Diagnostics. The event was offered free of charge and can be accessed on-demand at hc1.com/summit.

About hc1hc1 is the leader in critical insight, analytics, and solutions for precision health. The hc1 Precision Health Cloud organizes volumes of live data, including lab results, genomics, and medications, to deliver solutions that ensure that the right patient gets the right test and the right prescription. Today, the hc1 Platform powers solutions that optimize diagnostic testing and prescribing for millions of patients nationally. To learn more about hc1's proven approach to personalizing care while eliminating waste for thousands of health systems, diagnostic laboratories, and health plans, visit http://www.hc1.com and follow us on Twitter, Facebook, and LinkedIn.

Media Contact Liz Goar email: liz@npccs.com phone: 813-333-2844

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2nd Precision Health Virtual Summit Provides Look at Innovation Advancing the Promise of Personalized Medicine - Yahoo Finance

THOUSAND OAKS, Calif., Sept. 9, 2021 /PRNewswire/ --Amgen (NASDAQ: AMGN) will present at Morgan Stanley's 19th Annual Global Healthcare Conference at 2:45 p.m. ET on Tuesday, Sept. 14, 2021. Robert A. Bradway, chairman and chief executive officer at Amgen will present at the conference. Live audio of the conference call will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen's business given at certain investor and medical conferences, can be accessed on Amgen's website, http://www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

About AmgenAmgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to beone ofthe world'sleadingindependent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visitwww.amgen.comand follow us onwww.twitter.com/amgen.

CONTACT: Amgen, Thousand OaksMegan Fox, 805-447-1423 (media)Trish Rowland, 805-447-5631 (media)Arvind Sood, 805-447-1060 (investors)

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Amgen to Present at the 19th Annual Morgan Stanley Global Healthcare Conference - StreetInsider.com

Dame Sarah is already on the record as not being a fan of jabbing children for the sake of it. She has pointed out that countries should consider vaccinating the small number most at risk, but otherwise is not convinced of the benefits.

If you cant prevent transmission by vaccination and the children are not at risk of severe disease and hospitalisation and death, which the vast majority of children are not, you have to ask yourself: What would be the benefits of vaccinating children?, she told Italian newspaper La Repubblica in July.

We are not going to eradicate Sars-Cov-2. Its going to continue to circulate. And at some point, schools will remain open when there are infected children because, ultimately, we have to move to the point where we are living with the virus.

Dame Sarah first read about a novel virus spreading through the Chinese city of Wuhan on New Years Day 2020. She had designed a vaccine for it within two weeks, which was granted approval for use just 351 days later, one day before the year was out. Her own triplets, all studying biochemistry at university now, took part in the human trial.

A few stuttering months of confusion prior to the European Medicines Agency (EMA) declaring the overall benefits of Dame Sarah's vaccine outweighed the risks of one particular complication (developing a rare blood clot), with the risk of the rare clot from the vaccine eight times less than the risk of a clot caused by Covid-19, according to an Oxford University study Boris Johnson, Sir Keir Starmer, the Duke and Duchess of Cambridge and Dame Joan Collins included.

How frustrating it has been, then, for Dame Sarah who has since been lauded around the world, showered in medals and awards, had a Scientist Barbie designed after her, and even invited to sashay on to certain celebrity shows, of which more later to have been forced to spend the past year making clear that the vaccine is definitely safe, not having been chucked together in a lab at top speed like a cake made the night before the village fte.

Indeed, she and Dr Cath Green, associate professor in chromosome dynamics at the Wellcome Centre for Human Genetics at the University of Oxford and part of Dame Sarahs vaccine development team, have also taken the time to write Vaxxers (Hodder & Stoughton, 20), which explains clearly and in a very readable way how carefully and precisely the vaccine was developed.

We wanted to explain how we did this so fast, Dame Sarah explains. We appreciate it is natural for people to be hesitant.

But, in a nutshell, the vaccine came down to two things: advances in technology and development, combined with the reality of working in a pandemic: there was none of the normal hold-ups to slow down the team.

We were able to overlap processes that you would normally do sequentially, she says. We had less waiting to do between elements of work. But we still followed the normal regulatory pathway. Yes, we did it quickly, but we didnt miss any steps out. It is frustrating when people say development was too fast without saying why that would be.

Key to this was some unlikely help that came early on. At the start of January 2020, before the pandemic had been declared, Chinese scientists from Fudan University in Shanghai posted the fully sequenced genetic code for the new virus to enable the worlds scientists to move fast.

Vaccinologists, she says, are a close community. Weve always known that beating Covid was not winner takes all. There was no competition to come first. We need vaccines for everyone in the world.

This business-like approach is connected to Dame Sarahs biotech company Vaccitech, which she set up in 2016. Im a scientist to my core, she says, but Ive always wanted my science to make things better for people. Products can be developed better by a company than a university.

Vaccitech is already moving on, looking at way its vaccines could work in other conditions such as hepatitis B and prostate cancer. Thats the dream to have a targeted cancer treatment.

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Dame Sarah Gilbert: 'We don't need to give vaccine boosters to everybody. Immunity is lasting well' - Telegraph.co.uk

Indias genetic diversity is tied to language and social systems rather than geography, says study.  |  Photo Credit: iStock Images

India and its diversity have always been a subject of intrigue to the rest of the world, and a matter of pride for the Indians.

Genetic diversity varies substantially among Indian populations. So much so that at the continental level, the Indian continental group has significantly higher DNA diversity than European and East Asian groups put together.The study of the subcontinents population is of great interest to anthropologists purely because of the sheer size of the Indian population, the complex demographic history, and our unique social structures.

While research in the past has unravelled human genetic variation to a great extent, India's vast reservoir of genetic diversity still has a lot of scope to be explored.

The past genetic analysis of the Indian population had revealed that the diverse groups that we see today in India come from two major ancient populations the Ancestral North Indians (ANI) and the Ancestral South Indians (ASI). Basically establishing that geography is the biggest driver behind the genetic diversity of a population.

However, that is not quite the case, says research from Purdue University. The new study has now indicated that while the geography influencing genetic diversity'theory might stand true for European countries, it is not the case with India.

The study involved a unique model of interdisciplinary research bringing together genetics and computer science to consider jointly many different factors that may have shaped heredities. Using the model the Peristera Paschou, a population geneticist and associate professor of biological sciences at Purdue and Aritra Bose, a doctorate in both data science and genetics analysed a comprehensive dataset that represents the diversity of the Indian subcontinent.

The results opened a range of possibilities that were hitherto unknown. It revealed that in places like India, language and social systems like castes strongly affect how and where people live, implying that our genetic diversity is influenced more than just geography.

To put in perspective, if you know someones genetics among the European population, you can guess where they are from, to within a few kilometres in some cases, and if you know where someones ancestors came from, you have a close approximation of their genetic makeup.

However, in the Indian context, spoken language was seen as a major force in bringing people together in India besides the socio-demographic factors. Simply put, the results threw light on how the Indian people moved into India, and how various groups of people commingled. People who speak the same language (or even similar languages) here tended to be much more closely related, even if they lived far apart geographically.

Now, this model developed to analyse Indias population genetics is significant. Based on this, anthropologists will now be able to study other populations where genetics are not as closely tied to where one lives or hails from. Essentially the non-European populations with rich histories of diversity and migrations.

And this, in turn, will help us understand the history of human movement and cultures. You never know, it might even pave the way to understanding human health and susceptibility to disease, and pave way for advanced medical research where diagnosis and the treatment model will vary with each genetic group.

So, if you are an Indian or an Indian-origin person, dont go about trying to find your ancestors on the internet-based genetic and ancestry services. Those rely on the geography of ones forebears to determine our roots. India is more than just that.

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Indian genetic diversity is more about languages and social systems than just geography, says research - Times Now

Newswise The National Human Genome Research Institute has renewed its collaborative agreement with the Coriell Institute for Medical Research. For another five years, Coriell will continue to manage the NHGRI Sample Repository for Human Genetic Research, a collection of cell lines and DNA for use in research around the world.

The NHGRI Sample Repository for Human Genetic Research is a treasure for genetics research and its an honor to be selected to continue our role as the collections host, said Jean-Pierre Issa, MD, President and CEO of Coriell. The samples contained in this collection were used in several of the mostimportant studies in human genetics and its focus on increasing diversity in human genetics research is potentially transformative.

This collection was first established by NHGRI in 2006 as a public resource for scientists investigating human genetic variation carried by populations living around the world. Fifteen years later, it is still considered one of the most important resources in human genetics and genomics.

The NHGRI Sample Repository for Human Genetic Research contains unique collections of samples such as the landmark International HapMap and 1000 Genomes Projects, which are known for diverse DNA and cell lines characterized by large-scale genomic data.

The future of the NHGRI Repository is exciting, said Laura Scheinfeldt, PhD, Coriells Director of Repository Science and Principal Investigator of the collection. This important collection has supported the human genetics community for many years and will be an important resource to promote the inclusion of global genetic and genomic variation in studies of human health and disease for years to come.

In 2019, the NHGRI Repository joined the Human Pangenome Reference Consortium with Coriells contribution being led by Dr. Matthew W. Mitchell, the Co-Principal Investigator of this collection. This nationwide collaboration was formed in 2019 by distinguished researchers in the field of human genomics to improve the human genome reference sequence and continues to be an important collaborative effort for the NHGRI Repository team at Coriell moving forward.

Over the past five years, the NHGRI Repository has distributed tens of thousands of biospecimens to 47 countries around the world.

About the Coriell Institute for Medical Research

Founded in 1953, the Coriell Institute for Medical Research is a nonprofit research institute dedicated to improving human health through biomedical research. Coriell scientists lead research in personalized medicine, cancer biology, epigenetics, and the genomics of opioid use disorder. Coriell also hosts one of the world's leading biobankscomprising collections for the National Institutes of Health, disease foundations and private clientsand distributes biological samples and offers research and biobanking services to scientists around the globe. To facilitate drug discovery and disease study, the Institute also develops and distributes collections of induced pluripotent stem cells. For more information, visit Coriell.org.

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Coriell Institute Awarded $4.6 Million from National Human Genome Research Institute to Maintain Biobank - Newswise

NEW YORK Long-read sequencing can successfully provide diagnoses in previously intractable hereditary disease cases, according to recent studies, suggesting that long-read, whole-genome sequencing is on track to become the first-line genetic test of choice.

Last month, researchers led by Danny Miller and Evan Eichler of the University of Washington described the use of adaptive sampling on the Oxford Nanopore Technologies GridIon platform to identify previously undetected, disease-causing genomic variation in individuals who remained undiagnosed after a complete clinical genetics work-up. In some cases, this included exome sequencing or short-read whole-genome sequencing.

The team used a targeted approach to find pathogenic or "likely pathogenic" variants in six out of 10individuals with suspected Mendelian conditions and variants of unknown significance in two more.They also were able to identify previously known single-nucleotide variants, copy number changes, repeat expansions, and even methylation differences seen in prior testing of 40 patients, providing more detail on structural changes in about 20 cases.

"There's a cost in genetics of running multiple tests and bringing the patient back," Miller said. "This tech can simplify that process and make the analysis a lot more straightforward. It's beneficial for patients and families and for the healthcare system."

Their results, published in the American Journal of Human Genetics, are congruous with similar studies at the HudsonAlpha Institute for Biotechnology and Children's Mercy Hospital, each using long-read technology from Pacific Biosciences.

"We do find thatas presented here, too, that there is clinically significant genetic variation that is undetectable by short-read sequencing," said Tomi Pastinen, director of the Genomic Medicine Center at Children's Mercy. His team is working on a study of more than 200 cases and presented data on 100 patients at this year's American College of Medical Genetics and Genomics virtual conference. The data out so far are evidence that current methods of genetic testing for rare diseases, whether by short-read sequencing or microarrays, are incomplete, he said.

Pastinen suggested that the targeted approach used in the UW-led paper could be used as "a follow-up tool" for other tests or strong clinical hypotheses. "It's not aquantumleap," he said. "But they testeda number ofpositive controls,which isa nice feature."

Miller said the targeted method used by his team was more proof of concept and that long-read WGS "will eventually be theonly clinical genetic test we do," he said. "Because it's a single dataset, you can query multiple times."

Yet many challenges remain, including developing bioinformatics tools andreference datasetsand building a case for reimbursement.

As the name implies, long-read sequencing provides the ability to analyze longer stretches of the genome without having to piece them together from smaller parts, including regions where short reads crap out, such as repetitive regions. Those regions often contain so-called structural variants and many studies have shown that they are associated with disease, including cancers.

Long reads have been effective in detecting SVs but they have their drawbacks. Generally speaking, they offer lower throughput than short-read platforms and, until recently, had significantly lower single-read accuracy.

And they're not without blind spots. A recent study from the Human Genome Structural Variation Consortium published in the American Journal for Human Genetics analyzed SVs in samples from the 1000 Genomes Project. The study found that assembly-based methods of sequencing, which often are based on long reads, missed some large copy number variants that are detected with other methods.

Still, many researchers, like Miller, believe long read WGS is the future of clinical genetic testing, and the companies that make the technologies, namely PacBio and Oxford Nanopore, are driving proof-of-concept studies. In addition to its collaborationwith Children's Mercy, PacBio is working with Rady Children's Hospital in San Diego on a similar study. It has also partnered with Invitae to build an instrument for clinical long-read WGS. Oxford Nanopore, over in the UK, is developing its "Q Line" of instruments intended for clinical use.

Miller, a resident physician in the UW division of medical genetics with a doctorate in physiology, said he developed his chops on the Oxford Nanopore platform sequencing fruit fly genomes but "always had an eye on what I could do with humans, eventually."

The low barrier to entry made his study an "easier pitch, from the perspective of me, at my training level," he said. While Oxford Nanopore also offers ultra-long reads of up to 4 Mb, Miller said he was fine working with 50 kb to 60 kb reads. "They're very useful and I think they will be useful clinically."

For the study, Miller and his team used a special feature of the nanopore platform: the ability to preselect genomic targets and have the device spit out any reads that don't match. This "read-until" feature was introduced in 2014 but unlocked last year for targeted sequencing.

Miller said it's a fast and "straightforward" way of targeting sequences without using hybridization or amplification chemistries. "You just go to a genome browser, type in a gene, get the coordinates, and put it in a BED file," he said. "Then you're done." Moreover, it's pretty cheap. When purchasing reagents at scale, nanopore sequencing costs about $650 per sample, he said, compared to about $1,000 for short-read sequencing.

Pastinen said he wished the authors had compared the "real-life benefits of targeting reads versus doing Oxford Nanopore whole-genome sequencing."

One advantage of WGS is that it's unbiased, said Susan Hiatt, first author of the HudsonAlpha study, published in April in Human Genetics and Genomics Advances. "Whole-genome long-read sequencingis the best way to go for sure. You cando this targeted sequencing, too, if you know where to look."

In the study, her team found disease-causing structural variants in two out of six cases. "We had a guess there was some sort of structural variant, but we weren't looking for a particular gene or set of genes," she said.

"It's only six cases, so we don't know if that's the real diagnostic rate," Hiatt noted. Establishing a diagnostic yield will be a critical next step for the technology. Her team will be looking at another 200 probands over the course of the year using PacBio's platform. Already, they're seeing results. "It's showing us that we are going to find a significant number of variants," she said.

Finding variants is one thing, but putting them in context will be its own challenge. In the UW study, Miller said they were allowed to tell patients and their providers the study resultsif they wanted to receive them. "We clinically validated some of these findings, but in all cases, the institutional review board did not allow us to interpret the results," he said. "It's going to get even more challenging when we dowhole-genome sequencingand find novelstructural variants. How do you explaina complexexpansion of a repeat that altersmethylation? There will bea lot of interesting genetic counseling with long-read sequencing."

Improving the amount and availability of reference data will be key to making calls about clinical significance, Pastinen said. "In principle, you need reference data on similarly targeted but nonaffected samples," he said. "The data resources are not there yet for a robust rollout of all variants. Most of our reference data is our own data of a very small number of individuals. It's insufficient for high production level analysis."

But WGS had the benefit of generating reference data across the genome, which can be used for future cases. The All of Us project will be generating some long-read data from a "normal" population, but Pastinen said there needs to be more data sharing.

Bioinformatics tools are yet another resource the field still needs to develop. In addition to providing more data, HudsonAlpha's additional cases are giving the researchers a chance to experiment with different bioinformatics pipelines.

"There's a lot of different options out there. This will get us comfortable enough to say, 'This is the way we're going to go, so now we can scale it up,'" Hiatt said. So far, a lot of their pipeline comes directly from PacBio, including their SV caller.

And, of course, the field needs to do the ultimate head-to-head comparison with short reads, which would be a start to solving the problem of reimbursement.

"There hasnt, to my knowledge, been a systematic study comparing the incremental diagnostic rate of long reads over short reads," Miller said. "Thats probably what we really need to get payors to reimburse for the test."

"I don't know how insurance will respond," he added. "Justshowingwe can solve rare disease cases, I don'tknow if that's enough."

Excerpt from:
Studies Show Benefits of Long-Read Sequencing in Toughest Rare Disease Cases - GenomeWeb