Category Archives: Human Genetics

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May 6, 2022

Another lovely day at the University of Washingtons Seattle campus.Pamela Dore/University of Washington

Four faculty members at the University of Washington have been elected to the National Academy of Sciences. The new members from the UW are:

They are among 120 new members and 30 international members to the National Academy of Sciences this year. Election recognizes achievement in science by election to membership, and with the National Academy of Engineering and the National Academy of Medicine provides science, engineering, and health policy advice to the federal government and other organizations, according to an announcement May 3 by the academy.

Buffalo is noted for her research on the neural mechanisms behind learning and remembering. She studies how a system of structures in the brain, including the hippocampus and its surrounding cortical regions, set up new memories and how this system functions during memory retrieval. These structures are the first to be affected in Alzheimers disease. Lesions within these structures are associated with profound memory deficits. Her work may help improve the understanding of what foreshadows the onset Alzheimers and other dementias. She has a particular interest in how the brain maps surroundings, because getting lost in familiar locations is a common early symptom of Alzheimers. Buffalo earned her doctoral degree at the University of California, San Diego and did postdoctoral training in neuropsychology at the National Institute of Mental Health. She received the 2011 Troland Research Award for her innovative studies from the National Academy of Sciences.

Mougous is known for his research on how bacteria interact with each other in the environment and in our bodies. Much of his work focuses on the battles that occur within communities of bacteria. He examines the arsenals they deploy to attack each other and defend themselves. Among his areas of study are antibacterial toxins that disable target cells in a variety of ways, secretion systems that mediate antagonism between bacteria, and the toxins that virulent bacteria secrete to overcome host defense strategies. His laboratory also studies the densely populated mammalian gut microbiome, where conflict rages among microbes as bacteria compete for resources and struggle to survive. His lab is hoping to harness the antimicrobial tactics of bacteria to develop new therapies for infections and other purposes. Mougous earned his doctoral degree from the University of California, Berkeley. He is a Howard Hughes Medical Institute investigator and a researcher at the UW Medicine Institute for Stem Cell and Regenerative Medicine. In 2021, he received the National Institute of Sciences Award in Molecular Biology for his pioneering studies in microbiology.

Dr. Shendures research group has pioneered a variety of genome sequencing and analysis methods, including exome sequencing and its earliest applications to gene discovery for Mendelian disorders and autism; cell-free DNA diagnostics for cancer and reproductive medicine; massively parallel reporter assays; saturation genome editing; whole organism lineage tracing; and massively parallel molecular profiling of single cells. He has received numerous awards, including the 2012 Curt Stern Award from the American Society of Human Genetics, a 2013 National Institutes of Health Directors Pioneer Award and the 2019 Richard Lounsbery Award from the National Academy of Sciences. Dr. Shendure has been an advisor to the NIH Director, the U.S. Precision Medicine Initiative, the National Human Genome Research Institute, the Chan-Zuckerberg Initiative and the Allen Institutes for Cell Science and Immunology. He received his M.D. and Ph.D. degrees in 2007 from Harvard Medical School, where he trained with geneticist and molecular biologist George Church on advancing DNA sequencing techniques. He is currently an investigator with the Howard Hughes Medical Institute, director of the Allen Discovery Center for Cell Lineage Tracing and scientific director of the Brotman Baty Institute for Precision Medicine.

Trumans studies have focused on the genes, hormones and neural architecture underlying insect development and evolution. Early in his career, he identified the key hormone in moths that induces molting, as well as the brain-based circadian rhythms that exert overall control over this process. He later studied regulation of molting in the fruit fly and genes that control metamorphosis in moths. Truman earned a doctoral degree from Harvard University in 1970, where he continued as a Harvard Junior Fellow until joining the UW faculty in 1973. He became a full professor in 1978. He retired from the UW in 2007 and became a Group Leader at the Howard Hughes Medical Institutes Janelia Research Campus, where he studied nervous system metamorphosis in fruit flies. In 2016, Truman returned to the UW as a professor emeritus, and today continues to study the evolution and development of insects and crustaceans at the UWs Friday Harbor Laboratories. In 1970, he received the American Association for the Advancement of Sciences Newcomb Cleveland Research Prize and was a Guggenheim Fellow in 1986. Truman was elected to the American Academy of Arts and Sciences in 2009.

With this years addition, the National Academy of Sciences now has 2,512 active members and 517 nonvoting international members, who hold citizenship outside of the U.S.

Excerpt from:
Four UW researchers elected to the National Academy of Sciences for 2022 - University of Washington

SAN FRANCISCO, CA (IANS) Vineeta Agarwala, the wife of Twitter CEO Parag Agrawal, is now making headlines amid Elon Musks $44 billion takeover deal.

Her role as general partner at Andreessen Horowitz a VC firm which has agreed to pay $400 million as part of Musks new $7.1 billion financing commitments is set to create a conflict of interest.

As a general partner at Andreessen Horowitz, she leads investments for the firms bio and health fund across therapeutics, life sciences tools/diagnostics, and digital health, with a focus on companies leveraging unique datasets to improve drug development and patient care delivery.

Andreessen Horowitz is also one of the biggest backers of Meta.

Prior to joining a16z, Vineeta held many different roles in the healthcare space.

She was a physician, an operator at healthtech startups and investor at the Google Ventures life sciences team.

She was an early data scientist at Kyruus, a management consultant for biotech, pharmaceutical, and medical device clients at McKinsey & Co, and a director of product management at Flatiron Health.

She has collaborated with academic researchers at Cold Spring Harbor Laboratory, Lawrence Livermore National Laboratory, and the Broad Institute, where she did graduate work in computational biology and human genetics.

Vineeta holds a Bachelor of Science in biophysics from Stanford University, and MD and PhD degrees from Harvard Medical School/MIT.

She continues to see patients at Stanford as an adjunct clinical professor in the Division of Primary Care and Population Health.

Vineeta serves on several portfolio company boards, including BigHat Biosciences, GC Therapeutics, Memora Health, Thyme Care, Pearl Health, and Waymark.

Meanwhile, there are doubts over Parags future once Musk takes over, as the Tesla CEO himself can become a temporary CEO of the platform. According to reports, Musk may have also lined up a new Twitter CEO.

Parag is likely to receive nearly $39 million due to a clause in his contract once he leaves Twitter. His total compensation for 2021 was $30.4 million, largely in stocks.

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Parag Agrawal's Wife Vineeta Linked to Musk's Twitter Takeover - India West

When it comes to dog breeds, you may think you know your pups, but a study released this week confirmed what dog trainers and pit bull advocates have known all along: every dogs personality is special and unique!

If you live on this planet, youre likely to have encountered an enthusiastic dog owner oversharing all of the amazing things about their most loyal companion. While were totally on board with the concept that every child is exceptional, this specific breed of enthusiasm got University of Massachusetts geneticist Elinor Karlsson thinking just how much of a dogs personality is actually an inherited trait?

Karlsson and her stacked team of researchers from MIT, Harvard, and the Darwins Ark Foundation interviewed 18,385 dog owners about their canines behavior, including if theyre friendly with strangers, whether theyre possessive, if they enjoy retrieving objects, and even whether they circle before taking a poo.

No Toxic Traits Here!

After comparing the survey results to the DNA of 2,155 purebred and mixed breed dogs, the researchers found that while some breeds may show a greater tendency to howl, retrieve, or respond to human direction, only 9% of all personality traits were directly related to genetics or breed.

Considering there was zero evidence linking any breed with aggression, this study is great news for advocates of breeds like pit bulls and rottweilers, who are often banned by apartments, homeowners associations, and even entire cities.

Its a major advance on how we think about dog behavior, said Elaine Ostrander, who was not involved with the study but is a canine genetics expert at the U.S. National Human Genome Research Institute.

Much like humans, multiple factors come into play to influence a dogs personality, including its environment. So keep on snuggling!

From Wild Animal to Mans Best Friend

The history of dog domestication is lengthy, with evidence placing the beginning of the practice at around 20,000 years ago and some estimates going back more than 100,000 years!

In that time, selective breeding was commonplace with ancient humans breeding dogs for specific tasks, such as hunting, herding, and sitting on their laps. However, it wasnt until the 19th century that people began classifying the animals outside of these generic categories, and tracking their bloodlines.

What began as noblemen and shepherds breeding to improve these individual skills and amplify physical traits like coat color and texture and ear shape ultimately expanded to create the 400-plus designer dog breeds recognized today.

Considering the intentions behind breeding, wed like to submit a request for a part two of this study. If a dogs breed doesnt dictate its personality, does its owners personality dictate the breed of dog they get?

Well be waiting.

By Meghan Yani, contributor for Ripleys.com

FIND AN ATTRACTION NEAR YOU

Source: Research Shows Dog Behaviors Are Largely Unrelated to Breed

by Ripley's Believe It or Not!

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Research Shows Dog Behaviors Are Largely Unrelated to Breed - EverythingGP

Photo: Richard Dawkins, by Anders Hesselbom, Public domain, via Wikimedia Commons.

Editors note: We are delighted to present a series by geologist Casey Luskin on The Positive Case for Intelligent Design. This is the ninth entry in the series, a modified excerpt from the new bookThe Comprehensive Guide to Science and Faith: Exploring the Ultimate Questions About Life and the Cosmos.Find the full series so far here.

One potential objection to the positive case for intelligent design, developed in this series, is that Darwinian evolution might make some of the same predictions as ID, making it difficult to tell which theory has better explanatory power. For example, in systematics, ID predicted reuse of parts in different organisms, but neo-Darwinism also predicts different species may share similar traits either due to inheritance from a common ancestor, convergent evolution, or loss of function. Likewise, in genetics, ID predicted functionality for junk DNA, but evolutionists might argue noncoding DNA could evolve useful functions by mutation and selection. If neo-Darwinism makes the same predictions as ID, can we still make a positive argument for design? The answer is yes, and there are multiple responses to these objections.

First, not all the predictions generated by positive arguments for design are also made by Darwinian theory. For example, Michael Behe explains that irreducible complexity is predicted under design but predictednotto exist by Darwinism:

[I]rreducibly complex systems such as mousetraps and flagella serve both as negative arguments against gradualistic explanations like Darwins and as positive arguments for design. The negative argument is that such interactive systems resist explanation by the tiny steps that a Darwinian path would be expected to take. The positive argument is that their parts appear arranged to serve a purpose, which is exactly how we detect design.1

The same could be said of high-CSI features like protein sequences, which require rare and finely tuned sequences of amino acids to function. These are predicted by ID but are not expected under a blind trial-and-error process of mutation and selection.2

Second, the fact that a different theory can explain some data does not negate IDs ability to successfully make positive predictions. After all, a positive case means that the arguments for design stand on their own and do not depend merely on refuting other theories. While refuting competing hypotheses can certainly help solidify a theorys status as the best explanation, a positive argument must be able to stand on its own. IDs fulfilled predictions show there is positive evidence for design, regardless of what other models may or may not say.

Third, its not clear that in any of these cases neo-Darwinian evolution (or other materialistic models) makesexactlythe same predictions as ID. For example, in systematics, neo-Darwinism may predict the reuse of parts in different organisms, but it predicts that the distribution of parts will generally conform to a treelike pattern (or a nested hierarchy). Intelligent agents are not bound to distribute parts in a tree, and thus reuse of similar parts may be found even among very distantly related organisms. We can test among these different models. A 2018 paper by software engineer Winston Ewert in the journalBIO-Complexityproposed a model of common design called adependency graph, which was based on the technique used by software developers to reuse code among different software projects.3He compared the distribution of gene families reused in different organisms to a treelike pattern predicted by neo-Darwinismversusa dependency graph distribution used by computer programmers and predicted by ID. After analyzing the distribution of gene families in nine diverse types of animals, Ewerts preliminary analysis found that a common design-based dependency graph model fit the data 103000times better than a traditional Darwinian phylogenetic tree.4His ID-based dependency graph model predicted reuse of parts much better than neo-Darwinism.

Ewert tested the data against common descent. But even convergent evolution struggles to explain reuse of parts. Richard Dawkins acknowledges it is vanishingly improbable that exactly the same evolutionary pathway should ever be traveled twice,5yet we often find striking similarities across distantly related organisms, such as the camera-like structure of the vertebrate eye and the octopus (cephalopod) eye. What evolutionary biology calls extreme convergence is better explained by common design.

With junk DNA, its true that neo-Darwinian evolution predicts that functionality could sometimes evolve for noncoding DNA, and that finding function in a given case does not necessarily refute that model. Yet a major prediction of modern evolutionary theory is that neutral (neither harmful nor beneficial) mutations occur frequently and accumulate as useless genetic junk in genomes. For example, in 1972 the pioneering molecular evolutionary biologist Susumu Ohno published an article titled So much junk DNA in our genome. Writing in a volume titledEvolution of Genetic Systems,he argued that at the most, only 6% of our DNA is functional genes, with the rest being untranscribable and/or untranslatable DNA representing extinct genes or natures experiments which failed akin to fossil remains of extinct species.6

Biologists soon envisioned additional evolutionary mechanisms for filling our genomes with junk. In his influential 1976 bookThe Selfish Gene,Richard Dawkins predicted that a large fraction of our genomes has no function, because, The true purpose of DNA is to survive, no more and no less. The simplest way to explain the surplus DNA is to suppose that it is a parasite, or at best a harmless but useless passenger, hitching a ride in the survival machines created by the other DNA.7In 1980,Naturepublished two papers by influential biologists furthering the concept of selfish junk DNA. The first article, Selfish Genes, the Phenotype Paradigm and Genome Evolution, by W. Ford Doolittle and Carmen Sapienza, maintained, Natural selection operating within genomes will inevitably result in the appearance of DNAs with no phenotypic expression whose only function is survival within genomes.8A second paper, Selfish DNA: the ultimate parasite, was by Francis Crick, who won the Nobel Prize for determining the structure of DNA, and the eminent origin-of-life theorist Leslie Orgel. They concluded that much DNA in higher organisms is little better than junk, and it would be folly in such cases to hunt obsessively for its function.9Since that time, Darwinian thinkers have been seduced by the idea that parasitic DNA and random mutations will spread junk throughout our genomes. In 1994,Kenneth Miller published an article claiming that the human genome is littered with pseudogenes, gene fragments, orphaned genes, junk DNA, and so many repeated copies of pointless DNA sequences that it cannot be attributed to anything that resembles intelligent design.10Many similar quotes could be given showing that the idea of junk DNA was born, bred, and flourished from within an evolutionary paradigm.

As might be expected from such statements, the literature admits that evolutionary thinking has hindered research into functions for junk DNA.A 2003 article inScientific Americannoted that introns, a type of noncoding DNA found within genes, were immediately assumed to be evolutionary junk a view that the article later called one of the biggest mistakes in the history of molecular biology.11That same year, a paper in the journalScience observed that [a]lthough catchy, the term junk DNA for many years repelled mainstream researchers from studying noncoding DNA.12A striking admission came in a 2020 paper inNature Reviews Geneticstitled Overcoming challenges and dogmas to understand the functions of pseudogenes, which argues that dogma in biology causes demotivation into exploring pseudogene function by the a priori assumption that they are functionless. According to the paper, [t]he dominant limitation in advancing the investigation of pseudogenes now lies in the trappings of the prevailing mindset that pseudogenic regions are intrinsically non-functional and there is an emerging risk that these regions of the genome areprematurely dismissedas pseudogenic and therefore regarded as void of function.13

The ID communitys view of junk DNA stands in stark contrast to the typical evolutionary view. Going back to some of ID theorys early days in the 1990s, ID theorists have been predicting that noncoding DNA would turn out to have functions. In 1994, pro-ID scientist Forrest Mims submitted a letter toSciencethat warned against assuming that junk DNA was useless.14In 1998,William Dembski wrote that on an evolutionary view we expect a lot of useless DNA. If, on the other hand, organisms are designed, we expect DNA, as much as possible, to exhibit functionDesign encourages scientists to look for function where evolution discourages it.15Many other ID theorists have made similar predictions over the years. What might have happened if their predictions had been heeded?

In 2021, the journalNatureacknowledged that prior to the Human Genome Project (HGP), which was completed in 2003, there was great debate over whether it was worth mapping the vast non-coding regions of genome that were called junk DNA, or the dark matter of the genome. The article noted that over 130,000 genomic elements, previously called junk DNA have now been discovered, and highlighted how important these junk segments have turned out to be:

[I]t is now appreciated that the majority of functional sequences in the human genome do not encode proteins. Rather, elements such as long non-coding RNAs, promoters, enhancers and countless gene-regulatory motifs work together to bring the genome to life. Variation in these regions does not alter proteins, but it can perturb the networks governing protein expression With the HGP draft in hand, the discovery of non-protein-coding elements exploded. So far, that growth has outstripped the discovery of protein-coding genes by a factor of five, and shows no signs of slowing. Likewise, the number of publications about such elements also grew in the period covered by our data set. For example, there are thousands of papers on non-coding RNAs, which regulate gene expression.

Under an ID paradigm, debates over whether to investigate junk DNA would have ended much sooner with an emphatic Yes!, furthering our knowledge of genetics and medicine. When it comes to junk DNA, ID has made superior predictions.

Next, Does Intelligent Design Make Predictions or Retrodictions?

Originally posted here:
Does Darwinism Make the Same Predictions as ID? - Discovery Institute

It could be in their genes, posits Tangye. Genetic influences are either making people vulnerable to really severe disease but may also contribute to resistance there are populations of people who probably should have been infected and sick but werent.

Exactly which genes have a protective effect is part of an international research project called the COVID Human Genetic Effort, that Christodoulou is involved with.

We are collecting information and DNA from individuals who have been hyperexposed to COVID but who dont seem to contract COVID for example, living in a household where multiple family members were infected, but one member of the household wasnt to see if genetic factors can be identified that might offer protection against COVID infection, says Christodoulou, who is also the chair of Genomic Medicine at the University of Melbourne.

While researchers keep searching for the genetic clues, a new study published at the end of April, found booster shots can increase the range of immune cells, called memory B cells, making them more effective at neutralising COVID.

With any infection or vaccination, our body responds and then forgets the virus, explains Tangye, but becomes better at responding with repeated exposure. The first and second doses are like the training, getting your immune system into good shape and ready to take off and the third really gives you the protection you are primed and ready to go.

So if someone who has recently been vaccinated is exposed to COVID, they may be protected. If they have been boosted, this may provide even more protection, at least for a time.

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The degree of exposure how long we were in contact with someone and whether we were inside or out will also make a difference, as will our behaviour.

People have become much more cognisant of social distancing and washing their hands and wearing masks. There are those non-pharmaceutical interventions people have embraced, Tangye says.

As for how healthy you are generally, that unfortunately wont make us resistant to catching COVID.

We regularly hear of otherwise young, fit and healthy individuals contracting very severe COVID, says Christodoulou. For those otherwise healthy people we know that there are some factors that are associated with this, e.g., having so-called auto-antibodies to type 1 interferons (type 1 interferons are the first line of defence against COVID) or having mutations in genes that are involved in production and function of type 1 interferons.

Being healthy is good. But healthy people are still getting sick. Its not a panacea.

Interestingly, Tangye adds that there are people who naturally have this type 1 interferon pathway turned up a little bit: That can be pathogenic they can get these inflammatory diseases that dont have a defined triggerthese non-infectious, spontaneous flares for no good reason but people with those conditions may well have some resistance to COVID just because they have that innate immune response primed.

These people account for only a fraction of never COVIDs. For the rest, it seems to come down to a combination of immunity, genetics, environment and luck.

Being healthy all round puts you in better shape against infectious diseases and lifestyle disease, says Tangye. Being healthy is good. But healthy people are still getting sick. Its not a panacea.

Most of us may not be able to do much to avoid the virus, but we can still look to never COVIDs for some answers.

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If we can identify genetic reasons why people dont get COVID, it may help inform ways by which SARS COV2 enters or attacks our cells remember viruses are hopeless on their own. They need all the machinery of our cells to be disease-causing, explains Tangye.

So if we can disrupt the human cell processes without too many adverse events we could be better at stopping viral infection.

Make the most of your health, relationships, fitness and nutrition with our Live Well newsletter. Get it in your inbox every Monday.

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Havent had COVID yet? Its got to do with more than your T cells - Sydney Morning Herald

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Functional divergence of the pigmentation gene melanocortin-1 receptor (MC1R) in six endemic Macaca species on Sulawesi Island | Scientific Reports -...

Investigating the phenotypic and genetic associations between personality traits and suicidal behavior across major mental health diagnoses.

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Link:
The genetics of human personality - PubMed

The UCLA Science Hub for Humanity and Artificial Intelligence, a collaboration with Amazon, announced today its first cohort of 12 Amazon fellowships and six gift-funded research projects.

Funded by Amazon and housed at the UCLA Samueli School of Engineering, the UCLA Science Hub was launched last October, marking Amazons first such alliance with a public university. The hub was established to facilitate synthesis between industry and academic research on artificial intelligence to address societys most pressing challenges and develop solutions that will ultimately benefit humanity.

Twelve fellows were selected from a group of 25 UCLA Samueli doctoral students, and six research projects were chosen from 55 proposals by faculty across UCLA.

I am excited to see the mission of the hub, harnessing the power of AI for the good of humanity, being carried out through collaborations among UCLA faculty, graduate students and Amazon scientists, said UCLA Science Hub faculty director and computer science professor Jens Palsberg. Together, we will break new ground in addressing the societal impact of AI and find real technological solutions to improve humanity.

The Amazon fellows doctoral students in computer science, electrical and computer engineering, and mechanical and aerospace engineering will each receive up to two quarters of funding during the academic year to pursue independent research projects. They will also be invited to apply to intern at Amazon.

The inaugural cohort of UCLA Science Hub for Humanity and Artificial Intelligence Amazon Fellows and their research interests consists of:

See more here:
UCLA and Amazon Announce Inaugural Recipients of Research Gifts and Amazon Fellowships - UCLA Samueli School of Engineering Newsroom

On June 13, 2013, the U.S. Supreme Court unanimously ruled that human genes cannot be patented, in a case against Myriad Genetics brought on behalf of the ACLU and a group of interested parties, including Columbia University geneticist Dr. Wendy Chung. Dr. Chung saw the negative impact exclusive testing with a single lab had on patients, sometimes barring them access to genetic testing that could arm them with decision-making information about their diagnosis, treatment and care. Myriad held the exclusive licenses to the patents on the BRCA1 and BRCA2 genes, the most commonly affected genes in hereditary breast and ovarian cancer.

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At the time of the ruling, Dr. Chung said, This decision means we are not going to be impeded in giving full information to our patients about all of their genes. Reflecting on past progress and what is to come, Dr. Chung discusses the ever-evolving field of genetic testing and research, zeroing in on cancer.

Over the course of my career, the changes weve seen are profound, because when we started doing this, we didn't know about any cancer susceptibility genes, like BRCA1 or BRCA2. We knew that they must exist because we'd see families that seemed to have very strong family histories of cancer, and usually these were particular types of cancers, such as breast cancer running in the family or colon cancer, but we didnt know the exact genes or genetic variants. In my lifetime, I've seen first, the identification of those genes, and then second, the clinical implementation of genetic testing.

Most people are familiar with BRCA1 and BRCA2 genes, whether it's because they've heard of the Angelina Jolie story or they themselves know of someone with an increased cancer risk due to these genes. They were somewhat of a misnomer at the beginning, because they were named BRCA1 and BRCA2 for breast cancer 1 and 2, but they truly are breast and ovarian cancer genes. A lot of the infrastructure that was built around clinical implementation was built around those two genes, because those were the genes we knew about first and it was clear from a clinical standpoint what to do with that information. There were women who thought about having surgeries to reduce their cancer risk, whether that was a mastectomy [the surgical removal of one or both breasts] or oophorectomy [the removal of one or both ovaries]. Weve since developed programs to help those women make important decisions based on knowledge of their cancer risk profile. This ability really can be life-changing and lifesaving.

But those with mutated BRCA1 or BRCA2 genes arent in fact the majority of people who either get breast cancer or who are at risk for breast cancer. They're the peak of risk; having one of these genes puts you at the highest risk. We've since identified other genes that instead of increasing cancer risk by ten-fold, they might increase risk by two-fold. There's quite a different decision that patients make when you're at a two-fold increased risk rather than ten-fold. We've started building tailored care models, ways of educating people and thinking about different treatment and care management options based on a persons individual risk.

Yes, the second big wave in the clinical implementation of genetic testing was thinking about how you start to then integrate that information into clinical care, into routinization in terms of being able to provide a comprehensive genomic assessment for each patient diagnosed with cancer or at risk for cancer to tailor their treatment and care. For me, this second wave has really been for two different clinical use cases. One is people diagnosed with cancer and trying to think about their cancer management specifically. The other clinical use cases are people who don't yet have cancer, and hopefully, never will have cancer, but where we use this information in risk stratification to think about how to either reduce risk or screen for cancer and tailor that plan based on the individual and specific factors, everything from gender to stage in life to genetic and non-genetic risk factors and putting that all together.

For instance, within the Jewish community, we know that 1 in 40 people has a mutation in either the BRCA1 or BRCA2 genes. We have a very accurate understanding of the cancer risk profiles for this population. We even have curves to know over the life course when that risk starts becoming higher. So, this first wave of progress has been powerful, where we identified the BRCA1 and BRCA2 genes, knowing the cancers associated with them, knowing that in particular, Jewish communities were at higher risk. The same storyline has happened for colon cancer. Realizing that there are genes for colon cancer, weve routinized screening to identify which individuals with colon cancer may have genes that increase their risk of other types of gastrointestinal cancer, or uterine or ovarian cancer for the women. Were able to really understand the full cancer risk for them and their families.

We're just starting to get into a brand-new era, where historically we've done genetic testing for genes, like BRCA1 and BRCA2, that have a remarkably high penetrance, or in other words, very high likelihood that someone will get cancer. Were now getting to the point where we can use genetic and non-genetic information to come up with better cancer risk stratification for a larger number of people. That's a new concept in terms of thinking about not just individual genes or variants, but looking at something like 500 different genes or variants, and in a mathematical way, being able to look at the combination of those in an individual. We can take all of that data and apply algorithms to understand the cancer risk of that individual based on all those unique genetic contributions. We can now see not just one tree, but the entire forest.

Yes, this is precision prevention. Its information about your individual risk profile in sufficient detail so you can come up with a strategy to mitigate your risk and/or detect cancer at an early treatable stage. We can model the effect of various interventions including exercise, diet, smoking, and show someone how they can bend their personal curve to reduce their cancer risk.

One of my core beliefs is that people should be empowered to get information they need and to be able to make rational decisions about their health. The problem is that some of the direct-to-consumer products may not be clear in what they're providing. You might think you're getting something about your breast cancer risk stratification, but there's little scientific or medical information content in there. I worry about people who think they might have clean genes after taking a home-based genetics test and think they dont have to worry about going for their annual mammogram or having a colonoscopy. If you want to find your long-lost relatives or if youre adopted and you don't know your familys origin, then some of these consumer DNA products might be a good way to do that. Using these products to trace your ancestry and your roots can be useful, but dont depend on them for medical guidance.

The Human Genome Project. Im smiling because we just had a virtual session with President Clinton, [former NIH directors] Francis Collins and Harold Varmus, and Donna Shalala [former U.S. Secretary of Health and Human Services]. We had a whole session, thinking back to the Clinton era and reflecting on this major accomplishment. Bill Clinton was a strong advocate for the Human Genome Project, and it was during his administration that the first draft was completed.

The Human Genome Project fueled everything that I've talked about being able to find genes, identify genes, and being able to do better cancer risk stratification. That was one of the best investments we made as a scientific community and has been hugely impactful.

Weve taken a few baby steps, but I want to emphasize that right now my field is not fair and is not equitable. What I mean by that is we serve a wonderfully rich and diverse community here at the Herbert Irving Comprehensive Cancer Center and with the genetic testing that we do I cannot give equally useful information to all the patients who come to see me. If you happen to be of European ancestry, I can give you much better information than if you come to me and your roots are from Nigeria. The fundamental problem is that we don't have equal representation in the genetic data that we have to interpret what the DNA means. Right now, 80% of the genetic data we have on average people comes from individuals that represent 20% of the world's population. We should have 80% from 80%. Anyone other than individuals of European ancestry are underrepresented. To me, that is fundamentally not fair and not equitable. We have a lot of work to do there.

Originally posted here:
Seeing the Forest Through the Trees: Dr. Wendy Chung on Genetics and Cancer - Columbia University

A collection of human DNA variants tied to more severe cases of COVID-19 are also associated with other serious medical conditions such as those dealing with blood clots and faulty inflammatory responses, according to a new study. A summary of this analysis, which comes from stored genetic data from 600,000 people, is published in PLOS Genetics.

This work provides invaluable insights into the genetic architecture of COVID-19 risk factors and disease complications, a pressing need as the pandemic continues, says the studys lead author, Anurag Verma, an instructor in translational medicine and human genetics at the Perelman School of Medicine. The balance between the associations that we uncovered will be important as more therapies for COVID-19 are considered.

Data used in this study comes from the Million Veteran Program, which was established by the U.S. Department of Veterans Affairs. It is among the largest and most diverse biobanks (repositories of genetic information used for research) in the world, making it ideal for examining the various pieces of DNA that could be exploited by COVID-19.

With the variants associated with severe COVID-19 in hand, the researchers examined whether any other health conditions were more likely to be associated with them. To do this, they analyzed roughly 1,500 phenotypes, meaning the identifiable traits of a disease, which could be gleaned from an electronic health record.

Variants that had been associated with more severe COVID-19 in the ABO locus, a term meaning a genes position on a chromosome, were found to also be associated with the most other conditions. Patients with these variants were 33% more likely to have conditions like venous embolism and thrombosis, which both involve blood clots.

Some differences in association were seen when genetic ancestry was taken into account. The odds of someone having neutropeniaa condition in which a patient has a low count of the white blood cells used by the bodys immune systemwere 29% higher in those with African genetic ancestry who had variants in the LMNA locus. Those with European genetic ancestry who had the same variants did not share a higher association.

This story is by Frank Otto. Read more at Penn Medicine News.

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DNA analysis finds links between severe COVID and other conditions | Penn Today - Penn Today