Category Archives: Human Genetics

Three exceptional scholars at the University of Connecticut have been selected for the highest honor the university bestows on its faculty, the Board of Trustees Distinguished Professor.

Each year, the Office of the Provost seeks nominations from across UConn for the newest cohort of Board of Trustees Distinguished Professors. Candidates must excel in all three areas of research, teaching, and public engagement. A committee of faculty is charged by the Provosts Office to review and select each years honorees from among a competitive pool of nominees.

Honorees retain the title of Board of Trustees Distinguished Professor throughout their career at UConn and receive a $2,500 one-year stipend to be used by each recipient to further their professional activities. The number of available professorships each year is determined by the University by-laws. The Board of Trustees approved the latest cohort of honorees at its April 27 meeting.

The recipients for 2022-23 are as follows, with more detailed biographical information below.

The selection of each new class of Board of Trustees Distinguished Professors highlights how exceptional our faculty are at UConn. These are outstanding scholars who have made significant advancements in their fields, as well as in scientific discovery and community impact within and far beyond our university campuses. I am pleased to honor them with this recognition and congratulate them on this distinction, said Carl Lejuez, provost at UConn.

Laurinda Jaffe

In her research, Jaffe has repeatedly made discoveries that have been key to moving forward our understanding of the physiological mechanisms that produce a fertilization-competent egg and initiate embryonic development upon fertilization. Another major focus in her lab has been how membrane receptors and cyclic nucleotides function in the signaling pathways by which the cells that surround the oocyte in the mammalian ovarian follicle control meiosis. These discoveries have contributed greatly to our understanding of fertility mechanisms. They also provide important paradigms for understanding how cyclic nucleotides can coordinate intercellular communication in multicellular systems.

Over her career, Jaffe has published over 100 scientific papers and book chapters, including five single author or senior author original research papers in Nature and Science. In 2021, she was elected a member of the prestigious National Academy of Sciences in 2021, one of only three members at UConn.

Jaffe has actively participated in formal and informal teaching of graduate, medical and dental students at UConn Health as well as in the mentoring and laboratory teaching of doctoral students and postdoctoral fellows. She came to UConn Health in 1981 and has served UConn and the community for over 40 years. Early in her career, she developed and directed the medical and dental school curriculum in Tissue Biology, which was recognized by the 1988 Loeser Award for Outstanding Teaching. She has also contributed to the summer program for incoming medical students with disadvantaged backgrounds, a program designed to improve diversity in education at UConn Health. In 2018, she was honored with the Excellence in Research Mentoring award given by the UConn School of Medicine. Jaffe also serves on the Graduate Women in Medicine and Science steering committee and has led an initiative to advocate for an increase in endowed chairs for female faculty. For the past 14 years, she has chaired the organizing committee for the annual Richard D. Berlin Lectureship, a campus wide event that brings together many departments. In 2015, she helped to organize an event that brought author Rebecca Skloot and the family of Henrietta Lacks to the Storrs campus.

Rachel ONeill

ONeills work centers on how genomes function and evolve. She uses cutting-edge genomic, computational and imaging approaches to gain fundamental insights into chromosome biology and genome evolution in a wide variety of organisms. Her studies on the structure and function of chromosome centromeres, essential for proper chromosome segregation during cell division, have shaped the field of centromere biology. She is highly sought-after as a collaborator on large-scale national and international projects that require a high-level expertise in genome assembly curation.

ONeills work on repetitive DNA, which makes up about 50% of the human genome but is frequently dismissed as junk DNA, has had far-reaching impact, including on normal fetal and placental development, the discovery of novel retroelements, evolutionary breakpoints and chromosome evolution, and continuing challenges to the centromere paradox. She is part of the team that released the first complete human genome sequence, published in a series of papers in Science. Her 2010 publication titled Chromosomes, Conflict, and Epigenetics: Chromosomal Speciation Revisited, remains one of the most cited reviews from the Annual Review of Genomics and Human Genetics. Collectively, ONeill has published more than 100 peer-reviewed articles and led or contributed to projects that have brought over $23 million in extramural funding to UConn.

ONeill is also the director of the Institute for Systems Genomics (ISG). As Director of the ISG, she has developed multiple new degree programs, initiated core facilities and programs (including the SARS-COV2 Surveillance Program) and established the iGEM and Genome Ambassadors outreach programs. Most recently, ONeill organized and hosted Nobel Laureate Dr. Jennifer Doudna for the ISG Distinguished Lecture series, an event that attracted about 1,800 attendees for the live virtual presentation.

ONeill also is part of the team that spearheaded the COVID-19 testing efforts at UConn that have helped UConn remain safe, efforts that were widely praised throughout the country including by White House Coronavirus Response Coordinator (2020-2021), Dr. Deborah Birx.

ONeill has been recognized with several honors for her teaching, research and service, including a UConn Excellence in Teaching award, a Connecticut Women of Innovation Academic Leadership Award, and is an elected member of the Connecticut Academy of Science and Engineering.

Richard Pomp

Pomp has dedicated his career to promoting fair, efficient, and progressive taxation. States, cities, and countries have valued his guidance on building ethical and sound tax regimes. He is sought after both nationally and globally as a visiting scholar, advisor, and expert witness, counseling cities, states, Indian tribes, the U.S. Congress, the U.S. Treasury, the White House, the Department of Justice, the IRS, the United Nations, the IMF, the World Bank, and numerous foreign countries, including Zambia, Indonesia, Gambia, Mexico, the Philippines, India, the Peoples Republic of China, Vietnam, and the Republic of China.

He served as the hearing officer for the Multistate Tax Commission, revising the existing rules on state corporate income taxation and drafting alternative solutions. He helped design or draft the Navajo tax code, the Connecticut income tax, the Alaska personal income tax (adoption pending), and the federal Internet Tax Freedom Act. He was Director of the NY Tax Study Commission, and was described by the then-governor as the father of fundamental tax reform in NY. He was the only non-resident appointed to the California Commission on the 21st Century Economy. He participates in various capacities in Supreme Court litigation.

Pomp is a remarkably prolific author with 13 books and monographs and more than 140 publications in total. Pomps interdisciplinary work has been relied on by judges to justify their decisions in high-profile cases. His casebook, now in its ninth edition, has been translated in part into seven languages. His work has been described as challenging orthodoxy, exposing fallacies and myths, connecting seemingly disparate concepts, and fundamentally changing the professions views of classical problems.

He has won two awards for his teaching. His classes have been consistently described as transformative, inspirational, innovative, and creative, the reason for coming to UConn Law School.

His views are regularly sought by the media, including CNN, NPR, Bloomberg Radio, Sirius Radio, KCBS, The New York Times, The Wall Street Journal, The Washington Post, the Christian Science Monitor, the Los Angeles Times, the Minneapolis Star Tribune, The International Herald Tribune, and the Hill.

Pomp has received every major award in his field, including NYUs Outstanding Achievement in State and Local Taxation, the Bureau of National Affairs Lifetime Achievement Award, Tax Analysts State Tax Lawyer and Academic of the Year, the Council on State Taxations Excellence in State Taxation Award, and the Connecticut Law Tribunes Professional Excellence Award.

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Three Faculty Selected for Board of Trustees Distinguished Professorship - UConn Today - UConn

Eleven UCLA faculty members were elected today to the American Academy of Arts and Sciences, one of the nations most prestigious honorary societies. A total of 261 artists, scholars, scientists and leaders in the public, nonprofit and private sectors were elected, including honorary members from 16 countries.

UCLA had the second most honorees among colleges and universities, preceded only by Harvard. Stanford was third, UC Berkeley fourth, and MIT and Yale tied for fifth.

In February,UCLA was No. 1 in the number ofprofessors selected for2022 Sloan Research Fellowships, an honor widely seen as evidence of the quality of an institutions science, math and economics faculty.

UCLAs 2022 American Academy of Arts and Sciences honorees are:

John AgnewDistinguished professor of geographyAgnews research focuses on political geography, international political economy, European urbanization and modern Italy. Among his many awards is the2019Vautrin Lud Prize, one of the highest honors in the field of geography. In 2017, Agnew was selected to deliver UCLAs Faculty Research Lecture.

Walter AllenDistinguished professor ofeducation, sociology and African American studiesAllen, UCLAs Allan Murray Cartter Professor of Higher Education, is the director of UCLAs Capacity Building Center and the UCLA Choices Project.His expertise includesthe comparative study of race, ethnicity and inequality; diversity in higher education; family studies; and thestatus of Black males in American society.

Patricia GandaraResearch professor of educationGandara is co-director of the Civil Rights Project/Proyecto Derechos Civiles at UCLA and chair of the working group on education for the UCMexico Initiative. Her publications include the 2021 books Schools Under Siege:Immigration Enforcement and Educational Equity and The Students We Share: Preparing U.S. and Mexican Teachers for Our Transnational Future.

Wilfrid Gangbo Professor of mathematicsGangbos expertise includes the calculus of variations, nonlinear analysis, partial differential equations and fluid mechanics. He is the founder of EcoAfrica, an association of scientists involved in projects in support of African countries, and is one of the UC and Stanford University faculty members who launched the David Harold Blackwell Summer Research Institute.

Haruzo HidaDistinguished research professor of mathematicsHida is an expert onnumber theory and modular forms. A highly honored mathematician, he has spoken about his research at numerous international conferences and was the recipient of a Guggenheim Fellowship in 1991 and the Leroy P. Steele Prize for Seminal Contribution to Research from the American Mathematical Society in 2019.

Leonid KruglyakDistinguished professor of human genetics and biological chemistryDavid Geffen School of Medicine at UCLAKruglyak is UCLAs Diller-von Furstenberg Professor of Human Genetics, chair of the department of human genetics and a Howard Hughes Medical Institute investigator. He studies the complex genetic basis of heritable traits, which involves many genes that interact with one another and the environment, and his laboratory conducts experiments using computational analysis and model organisms.He has been the recipient ofmany awards, includingthe Burroughs Wellcome Fund Innovation Award in Functional Genomics, the Curt Stern Award from the American Society of Human Geneticsand the Edward Novitski Prize from the Genetics Society of America.

Peter NarinsDistinguished research professor of integrative biology and physiology, and ofecology and evolutionary biologyNarins research focuses on how animals extract relevant sounds from the often noisy environments in which they live. His numerous honors and awards include a Guggenheim Fellowship, theAcoustical Society of Americas2021 silver medal in animal bioacoustics and election to four scientific societies: the Acoustical Society of America, the Animal Behavior Society, the American Association for the Advancement of Science and the International Society for Neuroethology.

Bradley ShafferDistinguished professor of ecology and evolutionarybiologyShaffer, the director of theUCLA La Kretz CenterforCalifornia ConservationScience, is an expert onevolutionary biology, ecology and the conservation biology of amphibians and reptiles. His recent work has focused on conservation genomics of endangered and ecologically important plants and animals of California, global conservation of freshwater turtles and tortoises, and the application of genomics to the protection of endangered California amphibians and reptiles.

Blaire Van ValkenburghDistinguished research professor emeritus of ecology and evolutionary biologyVan Valkenburgh, UCLAs Donald R. Dickey Professor of Vertebrate Biology, focuses on the biology and paleontology of carnivorous mammals such as hyenas, wolves, lions and sabertooth cats. She is a leading expert on the evolutionary biology of large carnivores, past and present, and analyzes the fossil record of carnivores from both ecological and evolutionary perspectives.

George VargheseProfessor of computer scienceUCLA Samueli School of EngineeringVarghese, UCLAs Jonathan B. Postel Professor of Networking,devotedthefirst part of his career tomaking the internet fastera field he calls network algorithmics for which he was elected to theNational Academy of Engineeringin 2017, theNational Academy of Inventorsin 2020 and theInternet Hall of Fame in 2021. He is now working to jump-start an area he calls network design automation to provide a set of tools for operating and debugging networks.

Min ZhouDistinguished professor of sociology and Asian American studiesZhou, UCLAs Walter and Shirley Wang Professor of U.S.China Relations and Communications, is director of UCLAs Asia Pacific Center.Her research interests include migration and development,Chinese diasporas,race and ethnicity, and urban sociology.

These individuals excel in ways that excite us and inspire us at a time when recognizing excellence, commending expertise and working toward the common good is absolutely essential to realizing a better future, David Oxtoby, president of the American Academy of Arts and Sciences, said of this years honorees.

Membership is an honor, and also an opportunity toshape ideas and influence policy in areas as diverse as the arts, democracy, education, global affairs and science, said Nancy C. Andrews, chair of the academys board of directors.

The American Academy of Arts and Scienceswas founded in 1780 by John Adams, John Hancock and others who believed the new republic should honor exceptionally accomplished individuals. Previous fellows have included George Washington, Benjamin Franklin, Alexander Hamilton, Ralph Waldo Emerson, Albert Einstein, Charles Darwin, Winston Churchill, Martin Luther King Jr., Nelson Mandela and UCLA astrophysicistAndrea Ghez.

The academy also serves as an independent policy research center engaged in studies of complex and emerging problems. Its current membership represents some of todays most innovative thinkers across a variety of fields and professions and includes more than 250 Nobel and Pulitzer prize winners.

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11 UCLA faculty members elected to American Academy of Arts and Sciences | UCLA - UCLA Newsroom

The Roma people have long held a special fascination for population geneticists who study the frequencies of genetic diseases. The largest minority in Europe, the Roma number 10 to 12 million and live in scattered groups, mostly in central and southeastern Europe. A recent Comment in Nature, from a team at the University of Freiburg, explores how Europes Roma people are vulnerable to poor practice in genetics.A tragic history

TheRoma, once called gypsies, likely originated in the Punjab region of northwest India about 1,500 years ago. They traveled to Persia (Iran), then through Armenia to the Balkan peninsula, and reached the Iberian peninsula by the 15th century. Their genomes diversified as people joined along the way. After their arrival in Portugal and Spain, persecution began. It was the beginning of extreme discrimination and isolation that would unfold over the years.

The Roma and the Jews became the targets of the Nazi goal of racial hygiene. In1936, investigators at The Race Hygiene and Population Biology Research Centre drew pedigrees of these groups to form the rationale of a scientific basis for the final solution. German geneticists studied the Roma. Ferdinand Sauerbruch, nominated for a Nobel, submitted a grant proposal to conduct genetic and medical research in Auschwitz, which the Deutsche Forschungsgemeinschaft funded. Hundreds of thousands of Roma died in experiments.

The ending of enslavement of the Roma across eastern Europe beginning in the mid nineteenth century and economic and political changes in eastern Europe in the twentieth century also left their marks on gene frequencies.

Discrimination continued. In the 1970s, the Slovakian government began sending Roma children to schools for those with mild mental disabilities due to genetically determined disorders from inbreeding, according to government documents. Not until 2020 did investigation begin. Said one geneticist,

The slip from genetics to eugenics can happen quite easily.

Today in some nations in eastern Europe the Roma still live in ghettos, with low incomes and little access to quality health care and education. Some do not even have electricity or fresh water to drink.

Thetwisted history of the Roma has left marks on their genomes. In the parlance of DNA science, the Roma experienced a series of Founder effects as they migrated west, while their numbers winnowed through population bottlenecks fueled by discrimination. Even with others joining, reproduction stayed mostly among the descendants of those from India.

Over time, due to continual social isolation, the Roma genome came to include sections that were identical in DNA sequence on both chromosomes of a pair. This is a telltale sign, called runs of homozygosity, that shout endogamy relatives having children together, often without knowing it. Roma genomes today are about 80 percent European and 20 percent Indian.

The complex undulations of Roma movements across Europe and ostracism led to variations of single-gene conditions that are more prevalent, or even unique, among them. Nine disorders are caused by novel private Roma mutations, including forms of glaucoma, polycystic kidney disease, limb-girdle muscular dystrophy, and a few neuropathies.

The frequency of one disease in particular across Europe, galactokinase deficiency, recapitulates the journey of the Roma. I have a figure of it in my human genetics textbook to illustrate the effects of migration on a gene pool.

Galactokinase deficiency is very rare and causes serious symptoms among people in most of Europe, but a mild form in the Roma causes only cataracts in infants. It affects 1 in 1,600 to 2,500 of the Vlax Roma in Bulgaria, where 5% are carriers. But among all Roma people in Bulgaria, which includes several groups, the incidence is 1 in 52,000. Farther west in Austria, 1 in 153,000 people have it, and in Switzerland, even farther west, it is 1 in more than 2 million.

Carrier rates in some Roma groups for various conditions range from 5% to 15%. Thats high enough to justify newborn screening programs linked to early treatment, or education and carrier testing for conditions with no treatments, so people can lower their risks of having an affected child using prenatal diagnosis or other strategies. But that hasnt happened. By comparison, 4% of northern Europeans carry cystic fibrosis, for which newborn screening is routine.

The Roma have been ignored, marginalized.

A few geneticists have long recognized the plight of the Roma.

As a result of traditionally low socio-economic status and limited access of the Roma to health care, their unique genetic heritage has long escaped the attention of European medicine and is now being randomly discovered,

wrote Luba Kalaydjieva, professor of molecular genetics at the Western Australian Institute of Medical Research, and colleagues in a 2001 paper,Genetic Studies of the Roma (Gypsies): A Review. She is a Roma guru with an MD and PhD with nearly 200 publications. Medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe, she and her co-authors write. Genetic studies should consider cultural anthropology and social organization against the backdrop of population substructure and demographic history of the Roma to develop public health programs.

In BioEssays in2005, Kalaydjieva calls the Roma the invisible minority. Yet their DNA is valuable. Researchers have sampled it since the 1990s, often not informing the people of the purpose.

In many cases, particularly in the late twentieth century, data and samples were collected from people, including prisoners, without adequate consent or record of consent, and then given to research groups or placed in public databases,

said Veronika Lipphardt, from the University of Freiburg.

In 2022, Lipphardt and colleagues analyzed hundreds of published reports of research that used DNA from Roma people. They also probed five public DNA databases. Bioethical breaches were rampant:

DNA samples were collected without adequate or any consent, and the DNA sequence and other personal information deposited in public databases or shared with other researchers.

Some researchers told the people theyd get feedback on whether they were carriers for certain genetic diseases. That didnt happen.

Published papers persisted in using the term gypsies.

Some studies sampled only the most isolated people or the sickest, skewing conclusions about the general health of the Roma people.

Privacy was compromised. It was easy to cross-reference DNA information in public databases with disease-based databases to identify patients.

Roma people are overrepresented in forensic databases. More than half of entries in a Bulgarian database used to hunt criminals are from Roma, yet they are only 5% of the population.

No projects aimed to help the Roma people who gave DNA.

But change is coming.

Journals are retracting papers that used DNA from vulnerable people without consent. Vulnerable populations include Indigenous peoples, migrants, displaced people, and groups that are considered foreign in their home countries, such as the Kurds in Turkey and Uyghurs in China.

Projects using DNA information from vulnerable groups now have international oversight boards that include bioethicists, social scientists, forensic specialists, and most importantly, community members. They consider consent; DNA collection, analysis, and interpretation; sharing findings; benefits or harms to donors; and ability to opt-out.

Several other vulnerable peoples participate in projects that use their DNA.

TheNative BioData Consortium, founded in 2018, is composed of the nations leading Indigenous geneticists, including tribal experts in precision health, technology, law, policy, business, ethics, and cultural matters. DNA sequencer manufacturerIllumina helps build datasets that encompass all aspects of health; not just genes, but social determinants of health too.

The San, one of the oldest Indigenous groups, live in southern Africa. In 2017 they published a detailedcode of ethicssummarized inScience. They ask that respectful researchers engage with us in advance of carrying out research. There should be no assumption that San will automatically approve of any research projects that are brought to us. We have encountered lack of respect in many instances in the past. For example, researchers photographed young children and breastfeeding mothers, without consent.

The San also ask for clear communication of study results. We require an open and clear exchange between the researchers and our leaders. The language must be clear, not academic. Complex issues must be carefully and correctly described, not simply assuming the San cannot understand.

Transparency, of risks and benefits, is key. In the past, researchers have changed the course or goals of an investigation, didnt show the San papers before publication, and the work yielded no benefits to them, they write.

TheAustralia National Centre for Indigenous Genomicssums up their situation, which is universal. Their goal is harnessing the science of DNA to improve the health and well-being of Australias First Peoples.Our DNA. Our people. Our stories. Our way.

Thanks to Diana Fredriksson for the suggestion to write this article.

Ricki Lewis, PH.D is a writer for PLOS and author of the book The Forever Fix: Gene Therapy and the Boy Who Saved It. Check out Rickiswebsiteand follow Ricki on Twitter@rickilewis

A version of this article was originally posted atPLOSand is reposted here with permission. Find PLOS on Twitter@PLOS

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Roma 'gypsy' people of Europe have long held a fascination for geneticists. Here's why - Genetic Literacy Project

SANTA CRUZ After nearly 40 years of work, scientists have finally completed sequencing the human genome and UC Santa Cruz was at the center of it all.

The completion of the sequence gives an idea for the baseline of all human genetics. Humans are 99.9% identical genetically, according to UCSC Genomics Institute Director David Haussler. Therefore, while scientists have only sequenced the DNA of a human once, anyone can look at it and get a near indistinguishable snapshot of their own genetic code.

UCSC Chancellor Emeritus Robert Sinsheimer embarked on the quest in 1985. Karen Miga, an assistant professor in biomolecular engineering, completed the task at the end of March.

Its the greatest honor of my life, she said. What it turned out to be was this amazing walking with a whole group of people towards a historic moment. I feel lucky to be a part of that legacy.

The former chancellor had just finished sequencing the genome of a virus, which inspired him to gather a team to sequence the human genome in the mid-80s. However, that task would be much harder than the one he just completed.

The virus Sinsheimer sequenced only has a sequence of a few thousand DNA patterns, which is miniscule compared to the genome of human, according to Haussler. The human genome is comprised of 3 billion DNA sequences.

Haussler likened the task to a jigsaw puzzle, except this puzzle has 3 billion pieces and a corner piece is not as easy to find.

It gives you a feel for how hard this problem of putting together all the little snippets of DNA into the right orientation and figure out what the actual chromosome looks like how hard that problem is, said Haussler, who worked on the original Human Genome Project.

In fact, the puzzle is so complex that scientists from 20 different countries joined forces to sequence the human genome. That team became known as the Human Genome Project, and it officially launched in 1990.

Those scientists spent the next 10 years working on sequencing the human genome. Along the way, the Human Genome Project even faced competition against a private company, Solara Genomics, that sought to accomplish the same task but also find a way to monetize it.

That competition lead to further innovations in technology, which gave researchers the power to sequence the genome faster. While technology advanced, the task at hand still remained daunting.

That work was incredibly difficult because the genome was so huge and the technology could only read 1,000 bases at a time, Haussler said.

To put that into perspective, the first chromosome in the human genome is 250 million bases long, Haussler noted. Subsequent chromosomes continue to get smaller, but there are still an additional 22 chromosomes adding up to more than 3 billion bases.

However, in July 2000, researchers at UCSC accomplished what seemed unachievable. A student at the university wrote a program that helped the Human Genome project complete a first draft of the sequence by July 7, 2000.

That was incredibly important to us because now scientists got a glimpse of our human heritage, Haussler said. In fact, regular people got a glimpse at our human heritage without having to pay a subscription.

That first draft displayed roughly 90% of the complete human genome. The remaining 10% of the human genome was just out of grasp with the state of technology at the time. As a result, many people in the project gave up, conceding that there is plenty of information for modern medicine in the 90% of the genome sequenced.

Technological advancements and perseverance would later help Miga, who was a grad researcher during the original project, catalogue the remaining 10% of the human genome.

Miga formally launched her international consortium in 2019, co-led by Evan Eichler from the University of Washington and Adam Phillippy from the National Institute of Health. Unlike the Human Genome Project, this consortium was independently funded and achieved its success on the free time of each of the associates.

Its completely grassroots. This is just a bunch of scientists from around the world using their spare time, using their own money that decided that this was something that needed to happen, Miga said.

The team really leaned into their research as the COVID-19 pandemic gripped the world.

While many people were learning to make banana bread, Miga and her team were completing the jigsaw puzzle of human genomics. However, what was left over from the Human Genome Project were some of the hardest pieces of the puzzle.

It was really difficult to sequence these, put them together or just reconstruct the puzzle, Miga said. When youre putting a puzzle together and you have all the blue-sky pieces that look the same, thats what we were up against.

But of course, the hardest pieces to solve were some of the most important parts of human genetics. The parts of the human genome that Miga cataloged are some of the fastest-changing genetics through history, Haussler said. They are also parts of genetics that are vital to human life.

The parts of the genome Miga focused on focused on the centromere of cells, which makes sure cells separate properly during mitosis. When this part of the cell does not function properly, it leads to cancer and birth defects.

With this portion of the genome sequenced, scientists can begin to work on sequencing cancer genomes, which will lead to further advancements in cancer research.

This is the first time we can study the sequences in these important regions, Miga said.

But that is not where this project ends. With the complete sequencing of the human genome which Miga and her finished in roughly three years scientists now look towards the pangenome project.

That project aims to further diversify the information in the sequenced genome. The idea is to represent at least 350 diverse people from around the world, Miga said. While scientists are celebrating the completion of a single human genome, it does not capture the full diversity of human genetics, she added.

We all have our own ties to human history. These variants distributed around the world give us an indication of how humans have migrated for the past 1,000 years, she said. Were hoping this project will identify even more of those complicated regions we know are present but havent been able to study in the past.

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UCSC researcher completes human genome sequencing - The Mercury News

This article was originally published here

Philos Trans R Soc Lond B Biol Sci. 2022 Jun 6;377(1852):20200427. doi: 10.1098/rstb.2020.0427. Epub 2022 Apr 18.

ABSTRACT

The Apportionment of Human Diversity stands as a noteworthy intervention, both for the field of human population genetics as well as in the annals of public communication of science. Despite the widespread uptake of Lewontins conclusion that racial classification is of virtually no genetic or taxonomic significance, the biomedical research community continues to grapple with whether and how best to account for race in its work. Nowhere is this struggle more apparent than in the latest attempts to translate genetic associations with complex disease risk to clinical use in the form of polygenic risk scores, or PRS. In this perspective piece, we trace current challenges surrounding the appropriate development and clinical application of PRS in diverse patient cohorts to ongoing difficulties deciding which facets of population structure matter, and for what reasons, to human health. Despite numerous analytical innovations, there are reasons that emerge from Lewontins work to remain sceptical that accounting for population structure in the context of polygenic risk estimation will allow us to more effectively identify and intervene on the significant health disparities which plague marginalized populations around the world. This article is part of the theme issue Celebrating 50 years since Lewontins apportionment of human diversity.

PMID:35430888 | DOI:10.1098/rstb.2020.0427

Originally posted here:
Polygenic risk, population structure and ongoing difficulties with race in human genetics - DocWire News

April 13, 2022

In genomic studies, researchers examine the DNA of a population to understand the influence of genetics on health and disease. Though genomic studies have been common for more than a decade, most participants in these studies have been of European descent.

Dr. Lindsay Fernndez-Rhodes

Dr. Misa Graff

A new study led by Lindsay Fernndez-Rhodes, PhD, assistant professor of biobehavioral health at Penn State and 2016 doctoral graduate of the UNC Gillings School of Global Public Health, and Mariaelisa Graff, PhD, associate professor of epidemiology at the Gillings School, has shown that increasing the diversity of genomic samples can improve researchers ability to identify important genetic markers for health conditions.

One of the goals of conducting genomic studies is to develop precision medicine, which is the delivery of the exact treatment or medication that a person needs exactly when they need it.

Precision medicine is a great idea, but it only works if we study the full diversity of the populations that we may see in the clinic, Fernndez-Rhodes explained. We cannot treat people with precision if we do not have the relevant data. Previous large-scale genomic studies have largely overlooked Hispanic/Latino people. Since the United States is becoming increasingly diverse, our ability to provide appropriate medical treatment will suffer if the gaps in our genomic data are not addressed.

Fernndez-Rhodes and Graff were joined by more than 100 researchers from around the world to form the Hispanic/Latino Anthropometry Consortium. The consortium pools research expertise and genetic data on people of Hispanic/Latino ethnicity in order to bolster the diversity in genomic studies.

Dr. Kari North

Our consortium fills a major research gap in genomic studies. Inclusion of individuals of diverse ancestral backgrounds is imperative, both from the perspective of scientific necessity and equity, said Kari E. North, PhD, professor of epidemiology at the Gillings School, one of the consortiums multiple principal investigators, and co-author of this research. By embracing diversity, we are discovering novel genomic associations and moving the field forward.

In anew article in Human Genetics and Genomics Advances, Fernndez-Rhodes and Graff led the examination of genomic data from more than 70,000 Hispanic/Latino individuals. The data were compiled from 18 smaller studies and combined with two other consortia to bring the total sample to over 470,000 adults. To date, the article is the largest published genomic study of body measures in Hispanic/Latino individuals.

The researchers identified regions of the genome that are associated with three body measurements: body mass index (BMI), height, and waste-to-hip ratio. BMI, a ratio of weight to height, is the most common assessment of obesity used by physicians. Waist-to-hip ratio indicates where on their bodies people are carrying excess weight.

Consortium researchers identified 42 previously unidentified regions of the human genome related to BMI, height and waist-to-hip ratio. These traits have been examined in previous genomic studies, but the unique ancestry and experiences of Hispanic/Latino people made the regions easier to identify using the consortiums combined data.

The newly identified regions of the genome may help scientists understand how people grow, develop and perhaps most importantly for human health develop obesity. Significantly, the regions appear to be relevant to the health and development of all people, regardless of their ancestry. The researchers say that the results indicate a widespread need to build larger, more diverse data sources.

There is a very large gap between who is experiencing obesity and who is being included in genomic studies. The consortium is working to close one part of that gap. Hopefully, this is the first step of many toward increased diversity in genomic studies, said Fernndez-Rhodes. Researchers need to ensure that all people are represented in our scientific knowledge base. We need to harness the power of diversity to uncover the genes that pattern human health and disease.

Read the original release from Penn State.

Contact the UNC Gillings School of Global Public Health communications team at sphcomm@unc.edu.

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Greater diversity in genetic studies helps researchers uncover new insights - UNC Gillings School of Global Public Health

Advances in genomic technologies continue to expand the possibilities of PGT. In a preclinical research study recently published in Nature Medicine, scientists from Silicon Valley-based genetic testing companies have examined the potential of using PGT to predict complex polygenically inherited conditions in human embryos. While the authors present interesting data, Mina Popovic and Susana Chuva de Sousa Lopes from ESHREs SIG Stem Cells here report that the study raises profound medical, technical and ethical concerns.

Coupled to technical developments in embryo genomic sequencing, advances in complex trait genetics and computational genomics have now enabled the introduction of PGT-P for embryo selection. Nevertheless, the predictive value, clinical utility and ethical implications of this test remain highly controversial. Given the lack of compelling evidence for its clinical application, several scientific societies, including ESHRE and the European Society of Human Genetics, have recently released statements against the use of PGT-P in clinical practice.(1,2)

Despite these concerns, commercial genetic testing companies, including Genomic Prediction (https://www.lifeview.com), Orchid Health (https://www.orchidhealth.com) and MyOme (https://myome.com), have already introduced the technology to the market, offering PGT-P to prospective parents for a variety of complex diseases all in one test. Marketed as the most comprehensive preimplantation genetic test available today, PGT-P is now being used to screen embryos for their genetic predisposition to cancers, diabetes, heart conditions, schizophrenia, Alzheimers, as well as other adult-onset diseases. Remarkably, the selection of embryos based on non-medical conditions - such as cognitive ability, education and household income - have also been proposed, with a tenuous health benefit already assigned to some of these traits.

The technology behind PGT-P draws on polygenic risk scores, derived from large-scale genome-wide association studies.(3) These studies employ high-throughput genomic technologies to scan thousands of genomes obtained from different individuals to uncover genetic variants, predominantly single nucleotide polymorphisms (SNPs), that are significantly associated with a particular complex trait. Such data can be used to generate polygenic risk scores which summarise a set of genetic variants in an individual to evaluate their risk of developing a certain condition. Polygenic risk scores have inherently gained intense interest for preventative medicine, to improve diagnoses and select optimal treatment for a variety of common diseases. Applying this concept in the context of preimplantation genetics has thus enabled PGT-P. Nevertheless, very few studies have examined the utility of polygenic risk scores for embryo selection and ultimately the extrapolation of such data to an IVF embryo cohort remains problematic.(4)

In their recent study, Kumar and colleagues from MyOme combined molecular and statistical techniques to infer the whole genome sequence of 110 embryos, using parental genome sequencing and embryo genotyping.(5) They suggest that this method, known as whole genome reconstruction, can be used to more accurately predict susceptibility to 12 common polygenic conditions in human embryos, including cancers, cardiometabolic and autoimmune diseases. The study used samples from couples who had previously had PGT-A or PGT-M, while DNA was also available from ten children who had prior PGT. The authors validated their technique by comparing the reconstructed genome and polygenic predictions for the embryos to those of the corresponding children. Genome-wide prediction accuracy ranged from 98-99%.

The findings suggest that whole genome reconstruction improves the accuracy of risk predictions by comprehensively profiling embryo genomes, whilst overcoming known technical limitations associated with the genetic analysis of small amounts of embryonic DNA. The paper touches on challenges regarding the statistical validity of polygenic risk scores for evaluating embryos in this setting, and discusses some ethical aspects of the procedure. Nevertheless, many questions remain unanswered.

Alongside the paper, Nature Medicine published two commentaries highlighting the technical, clinical and ethical dilemmas associated with PGT-P.(6,7) These questions are complex and wide-ranging, and while it is not possible to give them full justice in this report, they certainly deserve serious attention.(8)

Despite the growing interest in polygenic risk scores in biomedical research, limited guidelines for performing such analyses have ultimately led to inconsistent data and misinterpretations of results. Accordingly, several methodological limitations in prediction accuracy hinder the clinical utility of PGT-P. Ultimately, polygenic risk scores only capture parts of the relevant genetic component of a condition. Indeed, predicting the risk of adult-onset diseases cannot account for changes in environmental or lifestyle factors which might occur over time. Moreover, predictions only provide a relative risk compared to the specific study population they were generated in. As justly mentioned by Kumar and colleagues, polygenic risk scores exhibit limited predictive accuracy when extended to different populations, as they have been largely developed using genome-wide association studies of European ancestry.

Studies have further shown that the potential gain of quantitative traits, such as height or cognitive ability, remains relatively small.(9) In addition, a substantial number of embryos per cycle (>10) is required to increase the prediction accuracy of PGT-P. This is largely unfeasible for many couples undergoing IVF. Moreover, as PGT-P screens for multiple polygenic conditions simultaneously, it vastly complicates embryo selection.

Currently, the complex relationships between genetic variants and traits are not well understood, and it is uncertain whether a lower risk for one condition may in fact increase susceptibility to others. Indeed, PGT-P creates enormous challenges for clinical management and patient counselling. Prospective parents will face difficult decisions as they try to balance risks for multiple conditions. Complicated decision-making surrounding embryo selection may dimmish procreative autonomy, lead to additional cycles of ovarian stimulation, and ultimately elicit unwarranted disposal of viable embryos.

Adequate ethical oversight and societal discussion also remain imperative. Accessibility to the technology, the opportunity for using PGT-P for non-medical individual traits, discrimination and stigmatisation of certain conditions, and drawing attention away from individual responsibilities for managing disease risk, all present legitimate concerns. Yet, research on the perceptions and attitudes towards PGT-P, including those of its consumers, is sorely lacking. In this increasingly complex industry, clinical decision-making must rely on preclinical and clinical studies, controlled trials, as well as longterm followup. Such studies inherently demand time, and remain challenging to perform, particularly in the context of assisted reproduction. Nevertheless, balancing innovation with robust evidence surrounding the effectiveness, safety and ethical implications of newly emerging technologies is becoming more relevant than ever.

1. See https://www.focusonreproduction.eu/article/ESHRE-News-PRS and https://www.eshre.eu/Europe/Position-statements/PRS2. Forzano F, Antonova O, Clarke A, et al. The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice. Eur J Hum Genet 2021; doi.org/10.1038/s41431-021-01000-x3. Tam V, Patel N, Turcotte M, et al. Benefits and limitations of genome-wide association studies. Nat Rev Genet 2019; 20: 46784. doi.org/10.1038/s41576-019-0127-14. Turley P, Meyer MN, Wang N, et al. Problems with using polygenic scores to select embryos. N Eng J Med 2021; 385: 7886. doi.org/10.1056/NEJMsr21050655. Kumar A, Im K, Banjevic M, et al. Whole-genome risk prediction of common diseases in human preimplantation embryos. Nat Med 2022; 28: 513516.doi.org/10.1038/s41591-022-01735-06. Gleicher N, Albertini DF, Patrizio P, Orvieto R, Adashi EY. The uncertain science of preimplantation and prenatal genetic testing. Nat Med 2022; 28: 442444. doi.org/10.1038/s41591-022-01712-77. Johnston J, Matthews LJ. Polygenic embryo testing: understated ethics, unclear utility. Nat Med 2022; 28(3): 446448. doi.org/10.1038/s41591-022-01743-08. Siermann M, Tuiko O, Vermeesch JR, et al. A review of normative documents on preimplantation genetic testing: Recommendations for PGT-P. Genet Med 2022: S1098-3600(22)00678-5. doi.org/10.1016/j.gim.2022.03.0019. Karavani E, Zuk O, Zeevi D, et al. Screening human embryos for polygenic traits has limited utility. Cell 2019; 179: 1424-1435.e8. doi.org/10.1016/j.cell.2019.10.033

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Still doubts over embryo selection based on PGT for polygenic conditions - ESHRE

Did Edward O. Wilson Harvard professor, iconic biologist, champion of global biodiversity promote racist ideas? For years, some scientists have suggested the very question is rooted in smear campaigns and misreadings of Wilsons work. Other scholars have argued that racism and sexism are apparent in Wilsons writing on human evolution.

Since Wilsons death in late December 2021, at the age of 92, the question has been subject to renewed debate, after an opinion piece in Scientific AmericandescribingWilsons dangerous ideas set off a backlash from some scientists.

Now, two separate pairs of researchers, drawing from Wilsons papers at the Library of Congress, have published details of correspondence in which Wilson privately supports a psychologist known for his racist work. It doesnt surprise me at all, said Joseph Graves, Jr., an evolutionary biologist at North Carolina Agricultural and Technical State University who haswrittenextensivelyabout scientific racism, and who reviewed some of the new archival work before it was published. Whats important about the new research, he added, was coming up with the smoking gun.

Not everyone agrees the new evidence is so definitive, but the revelations promise to prolong the reckoning over Wilsons legacy and to add to an ongoing discussion about how racism and sexism may have shaped entire fields of study.

Wilson may be best known for his widely praised research on ants, and for his push to protect biodiversity. But the scientists work on human evolution has been contested since 1975, when he published Sociobiology: The New Synthesis, a sweeping study of the evolution of social behavior in animals. The books final chapter, which aims to consider man in the free spirit of natural history, as though we were zoologists from another planet, touches on the evolutionary origins of language, territoriality, and other behaviors. In the chapter, Wilson wonders whether there could be marked genetic differences between socioeconomic classes. (He concludes theres little evidence thats the case.) And he speculates that some of the differences between human cultures could be rooted in genetic differences, calling for a discipline of anthropological genetics to explore the question further.

Wilson was touching on questions that remain deeply polarizing: To what extent are certain features of human societies, like xenophobia, altruism, or inequality, dictated by our genes? And can some of the complex variation among human groups, from IQ scores to incarceration rates, be explained by genetic differences, rather than by environmental and social forces? Many racist projects from the eugenics movement to Nazism to present-day White nationalism have argued that racial differences have deep genetic roots. Such pseudoscientific ideas continue to fuel popular racist canards, such as theideathat Black people have genes predisposing them to violence.

Today, theres a broad consensus among experts in human evolution that that race is a social construct, not a biological category, and that it is extraordinarily difficult to link specific genes to complex human behaviors. And some researchers and advocates warn that, absent better data, explorations of those questions often just reproduce old stereotypes or offer thin cover for bigoted ideas.

After the publication of Sociobiology, Wilson was subject to fierce criticism, including from some of his Harvard colleagues, who argued he had gotten out ahead of the scientific evidence and that his conclusions about the way biology shapes human behavior veered into dangerous territory.

Wilson pushed back against those charges, arguing that his work had been misunderstood and, in some cases, distorted. (To keep the record straight, I am happy to point out that no justification for racism is to be found in the truly scientific study of the biological basis of social behavior, he wrote in 1981, stressing his belief in a single human nature.) Despite the criticisms, Sociobiology was enormously influential: The book helped launch the field of evolutionary psychology, and it had a profound influence on the study of animal behavior and biological anthropology.

Less than a week after Wilson died, Monica McLemore, a health researcher at the University of California, San Francisco, published the op-ed in Scientific American describing Wilsons work as problematic, and calling on scientists to reckon with his legacy. In response, the science blogger Razib Khan wrote anopen letterchallenging the way McLemores piece characterized Wilsons work, including baseless accusations of racism. Dozens of prominent scientists signed the letter.

The open letter pitted a group of mostly White scientists against a Black colleague who had raised concerns about racism. McLemore, who has received threats and hate mail since her piece was published, questioned the judgment of the researchers who signed it. That reputable scientists would be sloppy enough to sign a letter that would bring that kind of hate to my stance in this current moment to me the naivete is huge, she told Undark in a recent Zoom conversation. (Khan did not reply to requests for comment.)

Some of the letters initial signatories retracted their names after learning of Khanspast connectionswith figures associated with white nationalism, including alt-right figurehead Richard Spencer and publisher Ron Unz.

Soon after, Wilsons own connections to the right-wing fringe upended the conversation again.

One pair ofresearchers who surfaced those connections, Howard University evolutionary biologist Stacy Farina and her husband, Matthew Gibbons, began reading sections of Sociobiology while stuck at home during the Covid-19 pandemic. They were taken aback by what they found.

I had read some chapters of Sociobiology as a grad student, said Farina. And theres a lot of really great science in there. Its a very interesting book. And I had no idea that the last chapter had any of that stuff in it. Part of her motivation for digging into Wilsons work, she continued, was a sense of gaps in her own training. I am frustrated with the lack of education about these issues in evolutionary biology.

Later, during a Library of Congress workshop for Howard faculty, Farina asked if the Library had archival material on Wilson. Sure enough, the institution holds his personal papers including boxes of documents related to the sociobiology wars. When she and Gibbons perused the collection, they were drawn to four folders labeled with the name of J. Philippe Rushton, a Canadian psychologist who, starting in the 1980s, published studies arguing that substantial genetic differences existed between racial groups.

Population differences exist in personality and sexual behavior such that, in terms of restraint, Orientals > whites > blacks, begins one 1987 Rushton paperpublished in the Journal of Research in Personality. His work would eventually be dogged by accusations of statistical flaws and ethics violations, and key papers were retracted.

In 2002, Rushton took the helm of the Pioneer Fund, an organization founded in the 1930s to promote eugenics, the idea that humanity can be improved by manipulating which people reproduce. He led the nonprofit until his death in 2012.

On weekends, Farina and Gibbons began returning to the Library of Congress. It was a nice little escape during the pandemic, said Gibbons, who works as a business development specialist for a public health organization. Head out in the morning, go to an early session, grab some lunch, and sort of freak out over what the morning session revealed, race the clock and try to document as much as we could before they kicked us out at the end.

The letters, Farina said, demonstrate a warm relationship between Wilson and the psychologist. In the correspondence, which dates from the 1980s and 90s, Wilson expressed support for Rushtons work, and lamented a stifling culture that, he suggested, had prevented him from speaking more freely, referring in one note to a leftward revival of McCarthyism. When Rushtons university seemed poised to sanction him for academic misconduct, Wilson sent letters in his defense. He also sent letters to drum up support for Rushton from colleagues at Harvard and at the conservativeNational Association of Scholars.

Unbeknownst to Farina and Gibbons, a pair of historians were also exploring the Wilson archive. In 2018, University of Illinois historian of science David Sepkoski began working with Wilsons papers while researching abookon biodiversity. Like Farina and Gibbons, he noticed and gravitated toward the Rushton folders.

Struck by what he was reading, Sepkoski began dropping scanned images of letters into a Dropbox folder he shares with Mark Borrello, a historian of biology at the University of Minnesota. Im sure I called you from the archives, and was like, Youre not gonna believe this, Sepkoski told Borrello during a recent Zoom conversation with Undark. The two began sketching out a book project on Wilson.

The correspondence, Sepkoski and Borrello now say, suggests that Wilson was carefully managing his public persona even as he quietly continued his dispute with his left-wing critics.

Providing comments on one Rushton paper which applied a famous Wilson theory, meant to examine reproductive differences between different species, to argue that Black and non-Black people pursue different reproductive strategies Wilson was effusive. This is a brilliant paper, he wrote, one of the most original and heuristic written on human biology in recent years.

Whether it can even be published in this or some other journal devoted to human sociobiology, Wilson wrote later in his comments, will be a test of our courage and fidelity to objectivity in science.

Earlier this month, spurred by the backlash against McLemore, Farina and Gibbonspublishedtheir findings in Science for the People Magazine, a left-wing outlet linked to the activist group thatprominently opposedWilsons work in the 1970s.

Days later, Sepkoski and Borrello published their ownessayin The New York Review of Books, with more details from the Wilson archives.

The reaction to the letters among the scientific community has been mixed. Some researchers suggested the revelations do not necessitate a substantial reevaluation of Wilsons legacy. Asked about the new letters, sociologist Ullica Segerstrale referred back to her influential 2000 book, Defenders of the Truth, which covers the dispute between Wilson and his antagonists. In thebook, Segerstrale challenges characterizations of Wilson as a racist thinker, and argues that his critics often failed to engage with the actual substance of his work. I stand by my general analysis in that book regarding the thinking and behavior of both E.O. Wilson and Science for the People, she wrote in an email to Undark.

At the blog Why Evolution is True, biostatistician Gregory MayerdescribedFarina and Gibbons findings as small beer. Wilson, he wrote, appeared to be primarily defending Rushtons academic freedom, not endorsing his ideas. To do so does not imply an identity of views, Mayer wrote. In a phone interview, he suggested that historians should focus on more pressing historical topics, such as Wilsons role in the development of a key concept in ecology, rather than his correspondence with a discredited Canadian psychologist.

For other scientists, though, the letters felt significant. Writing for Small Pond Science, a science and teaching blog, biologist Terry McGlynnreflectedon the letters impact. When navigating the whiter parts of the cultural landscape of biology, the general party line has often been that Ed was mostly right about sociobiology, but his ideas had been twisted by racists, and there wasnt anything he could do about that, he wrote.

But, he continued, its indubitable that the party line I have passively received over the decades simply does not comport with reality.

Not everyone found the content of the letters especially surprising. Indeed, close attention to Wilsons work and public statements, some scholars said, already provided ample evidence that he was sympathetic to ideas that most biologists now consider not just morally questionable, but scientifically unfounded.

In 2014, Wilson gave a warm blurb to then-New York Times science journalist Nicholas Wades book A Troublesome Inheritance. The book argues that Black people may be, on average, more impulsive and less hardworking than White or East Asian people, and that basic differences in human society why Haiti is poor, for example, and European countries wealthy are attributable to genetic differences among groups. Inreviews,debates, andpublic statements, experts in human evolution pilloried the book for misrepresenting the science. A notable exception was Wilson, who, in his blurb, praised Wade for exemplifying the virtues of truth without fear and celebrating human genetic diversity.

Thats pretty much out in the open, said Princeton University biological anthropologist Agustn Fuentes, who describes A Troublesome Inheritance as awful, racist, horribly unscientific. What has changed, he said, is the scientific community itself. The field, he said, is really hitting a peak moment of reflection, of engagement with the complexities of racism and sexism, and how its structured some of the basic ideas.

Indeed, a recentpaperin the journal Nature Ecology and Evolution, authored by faculty, staff, and graduate students in the Department of Ecology and Evolutionary Biology at UC-Santa Cruz, is titled Anti-racist interventions to transform ecology, evolution, and conservation biology departments. Recently, biologists have mobilized to change species names that honorConfederate officersand other figures with troubling histories.

Even just in the last two or three years, it feels like something has shifted, said Ambika Kamath, a behavioral and evolutionary ecologist at the University of Colorado-Boulder. Among other factors driving that change, she said, is that biologists from more diverse backgrounds are coming into the field.

Kamath is hopeful that the conversation around Wilson will spark broader introspection among her colleagues. The problem, she and some other researchers argue, goes far beyond Wilson. I dont really care that Wilson had racist ideas, because I know pretty much all of the people that I dealt with, when I was coming up through the science system, had racist ideas, said Graves, who in 1988 became the first Black American to receive a Ph.D. in evolutionary biology. Wilson was just one of many.

For now, more work from the archives may continue to flesh out a fuller picture of Wilsons life and thought. Speaking last week, McLemore, the author of the Scientific American op-ed on Wilson, said she was still getting hate mail and threats. All I wanted to do, she said, was to have a more nuanced discussion about the work.

Michael Schulson is a contributing editor for Undark. His work has also been published by Aeon, NPR, Pacific Standard, Scientific American, Slate, and Wired, among other publications.

A version of this article was originally posted at Undark and is reposted here with permission. Undark can be found on Twitter @undarkmag

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Viewpoint: E.O. Wilson's legacy under fire in some quarters after donated papers underscore fascination with racial differences and human diversity -...

There are many people who have never gotten COVID-19, despite repeated exposure. At the other extreme, there are lots whove gotten sick from the coronavirus more than once, despite being vaccinated and even boosted.

A lot of factors are at play, experts said, including genetics and variations in immune response. Scientists are working towards finding a clear answer.

Theres a difference between people who can never catch COVID, despite exposure, and those who are able to clear it out of their systems without ever knowing they had it. If this second category of people tested regularly, they might show positive for a day or two. Different factors are likely at play between the two groups.

Its so messy, Dr. Julie Parsonnet, an infectious disease specialist at Stanford University. We dont know how to differentiate between whether youre just lucky, really careful or if genetically something is different.

In one study, conducted in early 2021 and known as the human challenge study, 36 healthy young adult volunteers none of whom had been vaccinated or previously infected were deliberately given the virus that causes COVID-19 in their noses and tested frequently afterward to track infection. Remarkably, nearly half never got infected at all.

Researchers dont yet know why some of those participants didnt get COVID, and it remains to be seen whether the pattern holds for more infectious but milder variants like omicron.

People have different immune responses to COVID: Despite exposure, some dont seem to catch the coronavirus at all, while others, even vaccinated people, are getting infected several times. A Yale New Haven Health nurse administers a COVID-19 vaccine in this file photo.

Dr. Monica Gandhi, an infectious disease expert at UCSF, said its important to note that with many infectious diseases, including HIV, which she studies and treats, there are instances where people are exposed over and over but never get the virus.

In the case of HIV, this is because these people lack the receptors for the virus. That means no matter how much they are exposed, theyll never become infected because its physically impossible. Scientists say this is likely true with COVID, as well.

But for those who seem to be able to clear the virus so quickly they never knew they had it, differences in the behavior of the immune system could be the reason.

One study on health care workers who repeatedly tested negative found that these people had high levels of memory T cells the long-lasting cells of the immune system that remember a virus and protect against severe disease from previous, non-COVID coronavirus infections, which may have helped them fight off infection more quickly. But another study found that, especially in older patients, high levels of memory T cells can actually be a risk factor for severe COVID-19, as they can trigger a more severe immune response to the virus that overwhelms their systems.

Both situations could be true, and scientists dont yet know exactly why cross-reactive T cells may be helpful for some and detrimental for others, Gandhi said, though this mechanism is less important for people who are vaccinated, as vaccines generate COVID-specific T cells.

Part of what makes COVID so weird is our own immune system, Gandhi said. Were all just really different.

A prominent example of that is the way the virus behaves in children, she said. Children tend to have a different immune response to new pathogens than adults, she said, which means their lungs and immune system are less likely to get inflamed.

Another mystery, she said, is that only some people, especially children, seem to be able to produce effective cross-immunity T cells from other, non-COVID coronavirus infections. Doctors still dont know why some peoples systems do this and others dont.

We need to still look for other genetic factors, Gandhi said.

There also could be physiological factors, like the shape of the nose, how people breathe and what kind of mucus they produce, Parsonnet said, which have not yet been widely studied.

On the flip side, scientists dont yet understand why some people end up getting COVID several times, even after being vaccinated. Some people may have never fully cleared the virus, even if symptoms go away, causing them to test positive repeatedly. Others may just have more reactive immune systems.

Gandhi said that outside factors such as stress or pregnancy can play a role in how likely you are to become infected and sick from the virus, in much the same way that college students get ill around the time of stressful final exams.

People have different immune responses to COVID: Despite exposure, some dont seem to catch the coronavirus at all, while others, even vaccinated people, are getting infected several times.New Haven Fire Department Chief John Alston, Jr., gets the first dose of a Moderna COVID-19 vaccine from APRN Grace Grajales in front of the New Haven Health Department in this file photo.

We can be more or less susceptible throughout our lives, she said. Its multifactorial. All of these reasons could be at play.

But really understanding the nuances between whats genetic, whats a quickly cleared virus and whats just lucky will take intensive scientific studies, Parsonnet said. One such effort to discover exactly how genes affect the severity of COVID infection or whether you get it at all is underway, through a collaborative project called the COVID Human Genetic Effort. But the research is still in its early stages.

Right now, we just dont know the answer, she said. But people are really interested in looking at it.

Danielle Echeverria is a San Francisco Chronicle staff writer. Email: danielle.echeverria@sfchronicle.com Twitter: @DanielleEchev

Excerpt from:
COVID immunity: Why some people are never infected - Torrington Register Citizen

By Dennis Thompson HealthDay Reporter

MONDAY, April 18, 2022 (HealthDay News) -- COVID-19 is mainly known as a respiratory ailment, but a new study suggests the coronavirus can infect your intestinal tract for weeks and months after you've cleared the bug from your lungs.

In the study about 1 out of 7 COVID patients continued to shed the virus' genetic remnants in their feces at least four months after their initial diagnosis, long after they've stopped shedding the virus from their respiratory tract, researchers found.

This could explain why some COVID patients develop GI symptoms like abdominal pain, nausea, vomiting and diarrhea, said senior researcher Dr. Ami Bhatt, an associate professor of medicine and genetics at Stanford University.

"We found that people who had cleared their respiratory infection -- meaning they were no longer testing positive for SARS-CoV-2 in their respiratory tract -- were continuing to shed SARS-CoV-2 RNA in their feces," Bhatt said. "And those people in particular had a high incidence of GI symptoms."

A long-term infection of the gut also might contribute to long COVID symptoms in some people, Bhatt and her colleagues theorized.

"Long COVID could be the consequence of ongoing immune reaction to SARS-CoV-2, but it also could be that we have people who have persistent infections that are hiding out in niches other than the respiratory tract, like the GI tract," Bhatt said.

For this study, the research team took advantage of an early clinical trial launched in May 2020 at Stanford to test a possible treatment for mild COVID infection. More than 110 patients were monitored to follow the evolution of their symptoms, and regular fecal samples were collected as part of an effort to track their viral shedding.

Many other studies have focused on viral shedding in patients with severe cases of COVID, but this is the first to assess the presence of viral RNA in fecal samples collected from people with mild to moderate COVID, researchers said.

About half of the patients (49%) had COVID RNA remnants in their stool within the first week after diagnosis, researchers found.

But at four months following diagnosis, when no more COVID remained in their lungs, nearly 13% of patients continued to shed viral RNA in their feces.

About 4% still were shedding viral RNA in their feces seven months out from their initial diagnosis, researchers found.

Bhatt was quick to note that the RNA constituted genetic remnants of the coronavirus, and not actual live virus -- so it's unlikely a person's poop could be contagious.

"While there have been isolated reports of people being able to isolate live SARS-CoV-2 virus from stool, I think that that's probably much less common than being able to isolate live virus from the respiratory tract," Bhatt said. "I don't think that our study suggests that there's lots of fecal-oral transmission."

But the lingering presence of COVID in the gut does suggest one potential influence for long-haul disease, she said.

"SARS-CoV-2 might be hanging out at the gut or even other tissues for a longer period of time than it sticks around in the respiratory tract, and there it can basically continue to kind of tickle our immune system and induce some of these long-term consequences," Bhatt said.

Long COVID has become such an established problem that many major medical centers have established their own long COVID clinics to try to suss out symptoms and potential treatments, said Dr. William Schaffner, medical director of the National Foundation for Infectious Diseases.

"A very substantial proportion of individuals who recover from COVID acutely nonetheless have lingering symptoms, and they can involve an array of different organ systems," Schaffner said.

"These data add to the notion that the cells in the intestine may themselves be involved with COVID viral infection, and they could potentially be contributors to some of the symptoms -- abdominal pain, nausea, kind of just intestinal distress -- that can be one aspect of long COVID," he said.

Bhatt said the findings also have implications for public health efforts to predict emerging COVID outbreaks by testing a community's wastewater for evidence of the virus, and Schaffner agrees.

"If, as they say, about 4% of people seven or eight months later are still excreting viral remnants in their stool, it complicates the assessment of the density of new infections in a community," Schaffner said. "It's another thing we have to take into consideration and start looking at going forward."

But Dr. Amesh Adalja, a senior scholar with the Johns Hopkins Center for Health Security, doesn't agree that such long-term shedding in stool should affect the accuracy of wastewater COVID surveillance.

"I dont think that these findings change the value of wastewater surveillance, as weve already seen its value in real life," Adalja said. "Whats valuable about wastewater surveillance is the trend if it is increasing or decreasing, which isnt really impacted by this phenomenon."

The new study appears in the online journal Med.

More information

The U.S. Centers for Disease Control and Prevention has more about wastewater surveillance for COVID-19.

SOURCES: Ami Bhatt, MD, PhD, associate professor, medicine and genetics, Stanford University, Stanford, Calif.; William Schaffner, MD, medical director, National Foundation for Infectious Diseases; Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security; Med, April 12, 2022

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Coronavirus Found in Human Feces Up to 7 Months After Infection - WebMD