Category Archives: Human Genetics

Since the human genome was first mapped, scientists have discovered hundreds of genes influencing illnesses like breast cancer, heart disease and Alzheimers disease. Unfortunately, Black people, Indigenous people and other people of color are underrepresented in most genetic studies. This has resulted in a skewed and incomplete understanding of the genetics of many diseases.

We are two researchers who have been working to find genes that affect peoples risk for various diseases. Our team recently found a genetic region that appears to be protective against Alzheimers disease. To do this, we used a method called admixture mapping that uses data from people with mixed ancestry to find genetic causes of disease.

In 2005, researchers first used a groundbreaking method called a genomewide association study. Such studies comb through huge datasets of genomes and medical histories to see if people with certain diseases tend to share the same version of DNA called a genetic marker at specific spots.

Using this approach, researchers have identified many genes involved in Alzheimers disease. But this method can find genetic markers only for diseases that are common in the genomes of the study participants. If, for example, 90% of participants in an Alzheimers disease study have European ancestry and 10% have Asian ancestry, a genome-wide association study isnt likely to detect genetic risks for Alzheimers disease that are present only in individuals with Asian ancestry.

All peoples genetics reflect where their ancestors came from. But ancestry manifests as both genetic variation and social and cultural experiences. All of these factors can influence risk for certain diseases, and this can create problems. When socially caused disparities in disease prevalence appear across racial groups, the genetic markers of ancestry can be mistaken for genetic markers of disease.

African Americans, for example, are up to twice as likely as white Americans to develop Alzheimers disease. Research shows that much of this disparity is likely due to structural racism causing differences in nutrition, socioeconomic status and other social risk factors. A genome-wide association study looking for genes associated with Alzheimers might mistake genetic variations associated with African descent for genetic causes of the disease.

While researchers can use a number of statistical methods to avoid such mistakes, these methods can miss important findings because they are often unable to overcome the overall lack of diversity in genetic datasets.

Disentangling race, ancestry and health disparities can be a challenge in genome-wide association studies. Admixture mapping, on the other hand, is able to make better use of even relatively small datasets of underrepresented people. This method specifically gets its power from studying people who have mixed ancestry.

Admixture mapping relies on a quirk of human genetics you inherit DNA in chunks, not in a smooth blend. So if you have ancestors from different parts of the world, your genome is made of chunks of DNA from different ancestries. This process of chunked inheritance is called admixture.

Imagine color-coding a genome by ancestry. A person who has mixed European, Native American and African ancestry might have striped chromosomes that alternate among green, blue and red, with each color representing a certain region. A different person with similar ancestry would also have a genome of green, blue and red chunks, but the order and size of the stripes would be different.

Even two biological siblings will have locations in their genomes where their DNA comes from different ancestries. These ancestry stripes are how companies like Ancestry.com and 23andMe generate ancestry reports.

Because genome-wide association studies have to compare huge numbers of tiny individual genetic markers, it is much harder to find rare genetic markers for a disease. In contrast, admixture mapping tests whether the color of a certain ancestry chunk is associated with disease risk.

The statistics are fairly complicated, but essentially, because there are a smaller number of much larger ancestral chunks, it is easier to separate the signal from the noise. Admixture mapping is more sensitive, but it does sacrifice specificity, as it cant point to the individual genetic marker associated with disease risk.

Another important aspect of admixture mapping is that it looks at individuals with mixed ancestry. Since two people who have similar socioeconomic experiences can have different ancestry at certain parts of their genomes, admixture mapping can look at the association between this ancestry chunk and disease without mistaking social causes of disease for genetic causes.

Researchers estimate that 58% to 79% of Alzheimers disease risk is caused by genetic difference, but only about a third of these genetic differences have been discovered. Few studies have looked for genetic links to Alzheimers risk among people with mixed ancestry.

Our team applied admixture mapping to a genetic dataset of Caribbean Hispanic people who have a mix of European, Native American and African ancestry. We found a part of the genome where Native American ancestry made people less likely to have Alzheimers disease. Essentially, we found that if you have the color blue in this certain part of your genome, you are less likely to develop Alzheimers disease. We believe that with further research we can find the specific gene responsible within the blue chunk and have already identified possible candidates.

One important note is that the genetic diversity that plays a role in disease risk is not visible to the naked eye. Anyone with Native American ancestry at this particular spot in the genome not just a person who identifies as or looks Native American may have some protection against Alzheimers disease.

Our paper illustrates that gaining a more complete understanding of Alzheimers disease risk requires using methods that can make better use of the limited datasets that exist for people of non-European ancestry. There is still a lot to learn about Alzheimers disease, but every new gene linked to this disease is a step toward better understanding its causes and finding potential treatments.

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Mixed-ancestry genetic research shows a bit of Native American DNA could reduce risk of Alzheimer's disease - The Conversation US

This Virus Will Evolve: Concerns Grow Over Variants, New Surge Among the Unvaccinated

Just as public health officials feared, the combination of too many unvaccinated people and the more contagious delta strain of the coronavirus has led to new COVID-19 surges across the nation.

The vast majority of patients being hospitalized now for COVID-19 are unvaccinated, explains Sergio Segarra, M.D., the chief medical officer with Baptist Hospital, part of Baptist Health South Florida. And many of them are young adults in their 20s and 30s who are getting extremely sick.

Sergio Segarra, M.D., chief medical officer with Baptist Hospital, part of Baptist Health South Florida.

From the very beginning, that was a concern of mine that we do not get a substantial portion of the population vaccinated, said Dr. Segarra, who was interviewed by CNN this week on the latest surge in COVID-19 hospitalizations in Florida and nationwide.

The latest update from the Florida Health Department shows that 58 percent of the states population over the age of 12 has been vaccinated. Among the most populated South Florida counties, Miami-Dade registered a 73 percent vaccination rate; Broward 66 percent, and Palm Beach 62 percent, according to the latest data.

But there is a persistent group of people who, for whatever reason, are not getting vaccinated. The more people that get infected, the greater the likelihood that the virus evolves into more variants, said Dr. Segarra.

On Thursday, U.S. Surgeon General Vivek Murthy, M.D, released the first surgeon generals advisory of his time with the Biden administration, describing the urgent threat posed by the rise of false information about COVID-19 and vaccines. Misinformation has caused confusion and led people to decline COVID-19 vaccines, reject public health measures such as masking and physical distancing, and use unproven treatments, states the advisory.

The U.S. Centers for Disease Control and Prevention said this week that the delta variant is responsible for 58 percent of newly confirmed cases nationwide from June 20 through July 3. The COVID-19 vaccines approved for use in the U.S. effectively protects people from severe illness if they are infected with the delta strain of the virus, the CDC says.

With more people getting the virus, whether they get minor symptoms or get significantly ill and end up in the hospital, theres a greater chance that a variant is going to occur, explains Dr. Segarra. The virus will evolve.

The worse-case scenario, which fortunately has not occurred, says Dr. Segarra, is the emergence of a variant that is resistant to the currently available vaccines.

That hasnt happened yet, but thats something that does keep me up, says Dr. Segarra. Thats something that makes me worry. And I would hate to think that 10 years from now theyre going to say, Wow, those people back in 2021 could have gotten the vaccine, but they didnt. And now theres some terrible variant out there that is creating all kinds of havoc. So, that does worry me.

For more than a year since the beginning of the pandemic, researchers and clinicians have been trying to understand why some people develop severe COVID-19 illness, while others show few if any symptoms. Risk factors have included age and underlying medical conditions.

However, variations in the human genome have not been thoroughly investigated as a possible risk factor that determines a mild or severe response to a COVID-19 infection. That is, until now.

A new study published in Nature, led by the COVID-19 Host Genomics Initiative (HGI), confirms or newly identifies 13 genes that appear to play a role in susceptibility to the coronavirus, or that have an affect on the severity of illness. The researchers established international collaboration when the pandemic started to focus on genetics. This collaboration included about 3,000 researchers and clinicians and data from 46 studies involving more than 49,000 individuals with COVID-19.

HGI teams involved in the analysis include both academic laboratories and private firms from two dozen countries, including the U.S. Several of the 13 significant genes identified by researchers had previously been linked to other illnesses, including autoimmune diseases.

One example is the gene TYK2. Variants of this gene can increase susceptibility to infections by other viruses, bacteria and fungi, the studys authors write. Individuals who carry certain mutations in TYK2 are at increased risk of being hospitalized or developing critical illness from COVID-19. Another example is the gene DPP9. The authors found a variant in this gene that increases the risk of becoming critically ill with COVID-19. It is the same variant that can increase the risk of a rare pulmonary disease characterized by scarring of the lung tissue.

This study is important not only for advancing our understanding of human susceptibility to COVID-19; it also underlines the value of global collaborations for clarifying the human genetic basis of variability in susceptibility to infectious diseases, states a supplemental article to the study published in Nature.

Children represent a growing share of COVID-19 infections in the United States, while severe illness from the coronavirus remains rare among young kids and adolescents. Researchers caution, however, that studies are needed to determine long-term health effects of COVID-19 on children.

According to the American Academy of Pediatrics (AAP), children accounted for about 2 percent of infections at the onset of the pandemic last year. By the end of May of this year, kids accounted for 24 percent of new weekly infections, the AAP said. The cummulative percentage of COVID-19 cases involving children is about 14 percent, the organization states.

More than 4 million children have tested positive for COVID-19 in the U.S., 18,500 were hospitalized and 336 have died from the disease, according to the latest update from the AAP.

At this time, it still appears that severe illness due to COVID-19 is rare among children, the AAP states. However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.

The U.S. Centers for Disease Control and Prevention (CDC) recommends everyone 12 years and older should get a COVID-19 vaccination to help protect against COVID-19. At this time, children 12 years and older are able to get the Pfizer-BioNTech COVID-19 vaccine. In May, the CDC and U.S. Food and Drug Administration approved the use of the Pfizer vaccine for adolescents after a clinical trial involving 2,260 12-to-15-year-olds found that the Pfizer-BioNTEch vaccines efficacy was 100 percent. This official CDC action opens vaccination to approximately 17 million adolescents in the United States and strengthens our nations efforts to protect even more people from the effects of COVID-19, stated CDC Director Rochelle Walensky in a statement.

Tags: COVID-19, COVID-19 vaccines

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COVID-19 Roundup: The Unvaccinated Fuel Hospitalizations; Genetic Link to Severe Illness; and Children's Infection Rate - Baptist Health South Florida

Philipp Koellinger| Milwaukee Journal Sentinel

Here is a thought experiment for you. How much praise do you deserve for the good things that have happened in your life? And how much blame do you deserve for the bad? As a scientist who specializes in social genomics the study of how the interplay of genetics and social environments influences our lives I argue that much of what happens to us in life is really a matter of luck.

Many types of luck affect our lives: who our parents are; when and where we are born; whether the tornado that passed through our hometown hit our house or not. All of these types of luck are beyond our control. And yet, they shape who we are and what happens to us throughout our lives.

One fundamental example of luck is the set of genes we get from our parents. Everyone starts with a random combination of their parents genes that are fixed at conception and remain unchanged from that day forward. In other words, we get our start in life through a genetic lottery in which many outcomes are possible, but only one materializes.

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The results of this lottery have a big effect on your life. But they dont control everything. The relationship between our genes and the shape of our lives is far more complicated than that.

Lets start with what our approximately 22,000 genes do control. Among other things, they determine whether were born in a male or female body, if our eyes are blue or brown, and if we have freckles.

Genes also influence other things, such as how tall well grow and whether were prone to obesity, cancer, dementia, or other health conditions much later in life. We say genes influence rather than control these outcomes, because other factors like the quality of healthcare we receive in childhood and whether we eat enough good food in our early years also play a part.

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The influence of genes also extends to the human brain, which is probably the most complex organ that exists in any living creature on our planet. More than half of our genes seem to influence the brain in one way or another. They pre-wire the brain, and then our experiences and activities throughout childhood and adulthood rewire and adapt this amazing organ to our circumstances.

A useful analogy is to think of the brain as a book with thousands of pages. When were born, the book has chapter names and preliminary notes and themes scribbled throughout. As we grow up, we fill in the blanks with what weve learned and experienced. Sometimes, an entire chapter of the book may be erased or rewritten (perhaps because of a stroke or injury). But, for the most part, the main themes of the original book continue to develop throughout our lives.

The partial influence of genes on virtually every aspect of who we are is so well-known that scientists started referring to it as the first law of behavioral genetics. In the past few years, tremendous technological progress has made it possible to read a persons genetic code reliably, quickly, and inexpensively. This allowed scientists around the globe to collect samples of genetic data from millions of people. My team and our colleagues used that data to look for associations between genes and the many behavioral and socioeconomic outcomes such as educational attainment, risk-taking, happiness, or alcohol consumption.

Our results reliably show that genes seem to influence all of these outcomes. And yet, there is no single gene that makes a person smart, or start a business, or reach for a bottle of wine the moment they get a chance to do so. My teams research tells us that the real story is more complex and subtle than anyone would have thought just a few years ago.

It turns out that most outcomes are influenced by thousands of genetic variants, each of which has only a tiny effect by itself. But adding up all these tiny effects begins to explain a substantial part of the differences among the people we observed. We call some of these differences such as whether people go to college or are willing to take risks genetically complex traits because they are linked to a large number of genes and because the biological function of those genes is often still unknown.

Adding to the complexity, most genes influence more than one outcome. We found that some of the genes associated with educational attainment are also related to health outcomes such as dementia, cancer, and cardiovascular diseases, but we dont know why exactly. It could be that some genes that make us perform well in school early in life also protect our brains later in life from cognitive decline. It also may be that the protective effect of these genes actually works via schooling. Maybe a better education helps you afford a healthier lifestyle and also leads to a challenging job that requires you to exercise your brain constantly, which in turn may reduce the chance of being diagnosed with dementia later in life.

We still have a lot to learn. For example, how do genes and environments interact to give rise to the behaviors and traits we observe in people later in life? But one thing we already know for sure is that behavior and health are tightly related, and that these links can often be traced back to the specific genes we were born with, at least to some extent.

My long experience studying how life outcomes are affected by the random results of our individual genetic lottery makes me feel humbled by the good things that have happened to me. It also makes me skeptical when others claim that they deserve something or when they blame bad fortune on the person unlucky enough to be its victim. Instead, I find that modesty and sympathy for others are the most natural responses to the lessons that modern genetics continues to teach us.

Philipp Koellinger is a professor of public affairs at theLa Follette School of Public Affairs, University of Wisconsin-Madison.

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Luck of the draw: How the random results of the genetic lottery can influence a host of your life's outcomes - Milwaukee Journal Sentinel

We are rapidly approaching the day when scientists will have the technology to alter the genome of embryos to cure genetic diseases such as Huntingtons disease, sickle cell anemia, and cystic fibrosis before they take their painful toll. For good or ill, Chinese researcher He Jiankui has shown that it is possible to safely make simple edits to a babys genome in vitro.

A friend of mine has cystic fibrosis. Shes spent more time in the hospital than anyone I know. But her health battles, agonizing as they are, have also made her deeply empathetic, kind, artistic, and persevering. Would I spare her a life of pain by making a genetic correction at conception knowing that it might take from her some of what makes her special? Yes. Am making a judgment call that health is of greater value than depth of character? Also yes.

Perhaps Im wrong.

But the ability to make multiple, complex edits to enhance a childs DNA rather than to cure a disease is the next scientific frontier. Scientists will be able to edit a babys genetics to make her smarter, more athletic, prettier, whatever her parents value most.

Most people would agree it is better to be healthy than sick. Is being taller better than being short? Will 10 IQ points make someone happier? Which physical characteristics are most beautiful? Should we make these choices for someone else? What happens to those who arent upgraded?

The creation of a class of improved humans through genetic modification isnt much different than similar efforts attempted through eugenics in the last century. It will most certainly widen the gulf between the haves and have-nots. Only those who afford in vitro fertilization with genetic enhancement treatment would have access.

While genetic engineering has great potential to solve significant health, environmental, and agricultural challenges, it also has the potential for harm. Can the harms be mitigated? Time will tell. In the meanwhile, we have an obligation to examine the potential benefits and unintended consequences.

If you read one book this summer, make it Walter Isaacsons The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race. You dont have to know anything about genetic modification to dive.

Isaacson paints a vivid picture of the process of scientific discovery, the people who discovered CRISPR and harnessed it for gene modification, and the potential costs and benefits of this revolutionary biotechnology. By the end of the book, youll wish you could meet Jennifer Doudna, the scientist who, along with Emmanuelle Charpentier won the 2020 Nobel Prize in chemistry and the other scientists responsible for this discovery.

Beginning in the 1990s, scientists began to note an oddity in bacterial DNA. All DNA is made up of four different molecules called nucleotides: adenine, thymine, guanine, and cytosine. Think of them as an alphabet of four letters A, T, G, and C. From the smallest bacteria to the largest whale, the DNA of all living organisms and viruses contain anywhere from thousands to billions of base pairs of these same four nucleotides. They spell out, like a recipe book, how to make and maintain every living thing.

Scientists noticed that bacterial DNA contained segments of repeated letters which they called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). In between these repeated clusters are segments of DNA that match the DNA of the viruses that attack bacteria. Were not the only creatures to catch a virus; bacteria get infected by viruses, too. One would think that a tiny, one-celled bacterium would be defenseless against a virus but its not. Because of these special DNA sequences, bacteria can locate and slice up viral DNA that has invaded the cell.

Having made this discovery, scientists asked themselves: if bacteria can use this bio-mechanism to alter viral DNA, can we use it to alter DNA?

Turns out we can and CRISPR is faster and in many cases better than existing biotechnology used for this purpose. Scientists can snip out segments in the DNA of living cells. The process of adding DNA, however, requires additional steps.

The most promising use of CRISPR biotechnology, in my opinion, is in agriculture where there are fewer ethical concerns and extraordinary potential benefits for human health and the environment. By 2050, the world population will be 9 billion and genetic modification will provide the key to ensuring there is enough food to go around. Scientists are using CRISPR biotechnology to increase food production, to make plants and animals naturally resistant to disease (thereby decreasing pesticides and antibiotics), and to bolster plant resistance to adverse environmental factors such as hotter temperatures, drought, and flooding which are likely to increase due to global warming.

While those benefits certainly outweigh the potential for harm, some questions remain: Should we bring back extinct animals and plants? How will they impact other animals and plants?

These questions, however, are easier to answer than the heavier questions regarding editing the human genome, which must be addressed if the scientific community is going to reach an international consensus on limits.

Krista L. Kafer is a weekly Denver Post columnist. Follow her on Twitter: @kristakafer.

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Kafer: The scary, promising and not too distant future of gene editing technology - The Denver Post

In absorbing new popular science title The Genome Odyssey, Stanford University Professor of Medicine and Genetics Dr Euan Angus Ashley reveals how our understanding of the human genome is revolutionizing medicine, finally unlocking the answers to mystery illnesses and leading to exciting new treatments for many of todays most devastating diseases.

In 2003, an international project to sequence the entire human genomeall thegenetic instructions found within thehuman bodywas finally completed.

It had taken a decadeof research,and had costseveral billion dollars to realise, but the effort was rightly recognised as one of the greatest scientific achievements in history, on a par with the first Moon landing.

It was nothing short of a giant leap in our understanding of genetics and came with theexpectationthat this knowledge couldone daybe used to treat or even prevent thousands of diseasesfrom the most common killers to the rarest conditions, affecting only a handful of people across the planet.

AsThe Genome Odyssey: Medical Mysteries and the Incredible Quest to Solve Themreveals, that early promise is now fast becoming reality, opening up a bold, exciting new era of genomic-based medicine that willtotallytransformsociety and our quality of life.

And who better to provide a guided tour to thisunfoldingmedical revolution than one of the worlds leading experts on genetic-based medicine: Dr Euan Ashley.

Dr Ashley, who was born in Scotland but who is now based in the United States,is recognised as apioneerin the application of gene sequencing in medicineandis right at the forefront of the field, beingProfessor of Medicine and Genetics at Stanford University, the Head of Stanford Center for Undiagnosed Diseases,andthe founding director of the Center for Inherited Cardiovascular Disease as well as Stanfords Clinical Genomics Program.

He joinedStanford totrain as a cardiologist in 2006, after completinga Ph.D. at Oxford University in cardiovascular biology, and has witnessed first-hand how rapidly genomic medicine has become integrated into healthcare.

Early on in the book, which has just been published through St. Martins Press, Dr Ashley observes through analogy that the growth of the sector has all been made possible thanks to the huge drop in the cost of sequencing an individuals DNA. He writes

My commute, at the time, took me past the Ferrari-Maseratidealership near Athertonbillionaire territory inthe heart of Silicon Valley. I would oftencast a sideways glance at thosecars as I waited in traffic. One day, I wassitting at the stoplight doingrandom math in my head, as one does, and realized that if the Ferrariin the window had dropped in priceas much as human sequencing haddropped in price in the eight years since the Human Genome Projectsdraft sequence was released, instead of $350,000 it would cost less than forty cents. A forty-centFerrari! A millionfold reduction in price.

He goes on to say that this incredible reduction in cost has fuelled a tsunami of scientific discovery which has given the medical profession an unparalleledopportunityto change lives for the better.

The Genome Odysseyunderlines just how dramatic that change has been, bringingnewfound hopeto people around the world.

Running to around 400 pages in length, the book is divided into four sectionswith the first,The Early Genomes, introducing the readerto the medical team that Dr Ashley leads and providing an account of their first steps into genomic-based diagnosis.

In anothers hands the subject could easily have become complex, dry,and off-putting but Dr Ashley wisely makes the patient the focusfrom the get-go , presenting thepersonal stories ofthosewho have benefitted from thisnew era of medical treatments to illustrate clearly how genomic medicine is actually making aprofounddifference to peoples lives.

Take, for instance, Parkera young boy who hadseemingly been a healthy babyupon deliverybut who, asthe weeks and months progressed,began to showclearand worryingsigns of developmental delay.

By the time his parents met with Dr Ashley and his teamfive years laterthey had gone from pillar to post to try to find out what was wrong with their son, who was alsonowsuffering alarming seizures. Despite numerous and often painful tests, all the medical professionals had drawn a complete blank.

Dr Ashleys team sequenced Parkers DNA from a blood sample and from this were finally able to give his parents the answers they had desperately been seeking.It turned out that he had a new type of genetic mutationdisruptingagene called FOXG1.

With this diagnosis, which would never have been possible before the Human Genome Project, Parkers parentscould tap intoa small yet international support network offamilies suffering fromFOXG1 syndromeand, more importantly, have his medication modified, resulting in their childs symptoms beingdramatically reduced.

As quickly becomes clear,the dedicated teams at the forefront of genetic medicine are akin to detectives, finding the culprits behind diseases within our genes.

Fittingly, then, the second section ofThe Genome Odysseyis entitled Disease Detectives and covers the fascinating procedural work involved in solving rare, mysterious diseases and, by so doing, ending the agonising diagnostic odysseysthat these patients have been sent on, such as was the case with Parker.

Here, we meet other families such as theparents of Carson and Chase Miller, whose two young sons had been losing their mobility yet the reason for this was unclear. They were referred to Dr AshleysCenter for Undiagnosed Diseases, which is itself part of a wider Undiagnosed Diseases Network in America, whereboth children and parents had their DNA sequenced.

From this they found that Carson and Chase had both inherited one faulty copy of geneMECRfrom each of their parents. That, in itself, did not solve the crime but this swiftly followed as the team interrogated the evidence, working out that this gene was essential to the smooth running of mitochondriathe energy-producingpowerhouses of the celland, with other possible causes for the boys condition being ruled out, the wrongdoer in question.

The case closed, attention could turn to treatment. Remarkably, it was deduced that a cheap over-the-counter supplementcould compensate for the missing protein that MECR would normally produce. The boys were placed on this and, as Dr Ashley writes with delight, they have sincestabilisedand even shown signs of improvement.

When not working on unsolved diseases, Dr Ashley deals with patients with genetic-based heart problems. This is the focus of the third part ofThe Genome Odyssey, Affairs of the Heart and, again, presents many moving patient stories, such as that of a baby girl,Jazlene,whose dangerously abnormal heart rhythm was rapidly traced to a genetic cause.

Thanks to the advent of cheap, fast genetic testing, new and fine-tuned treatments can now be provided to patientsbut this is only the beginning.

The final section ofThe Genome Odyssey, Precisely Accurate Medicine,projects forward, examining where genomic medicine will progress from here.

While gene therapy, replacing missing or faulty genes, is already available for a very limited number of conditions, ongoing research and refinements looks set to expand the scope for this treatment significantly in the coming years, potentially finding new, more effective ways to deal with a host of diseases including heart disease, multiple sclerosis, and certain types of cancer.

Key to this, it turns out, will be sequencing the DNA of genetic superhumans whose unique genomeprotects them from certain diseases or provides other physiological advantages.

Dr Ashley recounts, for instance,he story ofFinnishcross-country skier Eero Mantyranta, whose blood contained far moreoxygen-carrying red blood cells than the average person, allowing far greater levels of endurance.

We also learn about American womanSharlayne Tracy, who was found to have a superhuman ability to remove bad cholesterol from her body. Her genetic code has, in turn, led to new drugsfor treatingthose who are genetically prone tohigh cholesterol.

And in a very timely section, Dr Ashley reveals how genome sequencing can also be used on viruses to help us track and avoid future pandemics, just as it has been crucial in the development of vaccines for Covid-19.

Its amazing to discover just how far-reaching the unlocking of our genetic secrets will be for 21stcentury medicine, allowing doctors to move fromreactive disease care to proactive preventive health carethat will undoubtedly save many lives and allow us all to stay healthy for much longer.

The Genome Odysseytells this story in such an engaging way that the chapters just fly by. This is all helped by Dr Ashleys personable, almost conversational style, his passion for the subject, and his admiration for the heroes of this book, as he describes themhis patients and their families.

You come away from thishighlyinformative, entertaining, and unforgettable scientific journeywith the sense that we are heading into brighterdaysand all thanks to figures such as Dr Ashley who are tirelessly peeling back the mysteries of our DNA to overcome the diseases that have plagued us as long as mankind has existed.

The Genome Odyssey: Medical Mysteries and the Incredible Quest to Solve Them(St. Martin's Press)by DrEuan Angus Ashleyis out now onAmazon in hardcover, eBook, and audiobook formats, priced 22.99, 9.49, and 20.47 respectively. For more information visitwww.genomebook.info.

Q&A INTERVIEW WITH DR EUANANGUSASHLEY

We speak with Dr EuanAngusAshley,Associate Dean and Professor of Cardiology andGenetics at Stanford University,to find out more about his new work of popular science,The Genome Odyssey, and the genomic medicine revolution taking place right now.

Q. Why was the decoding of the human genome essential for the development of genetic medicine?

Its hard to think of a time in the history of biomedical science whena technology has moved so fast,from requiring multiple countries, hundreds of people, and billions of dollars to something that can be routinely ordered by a physician in clinic for $500.

But while the scientific narrative is exciting, its the human impact that made me want to write the book. I get to see every day how this technology can solve medical mysteries for kids and adults afflicted with devastating genetic diseases. I see how it can provide answersand provide a path to treatment (or if not, at least towards support groups and help). These are the medical odysseys of thetitle, a word derived from the epic Greek poem of the same name where the lead character takes 10 years and multiple shipwrecks and battles with, among others, one-eyed giants to get back to his home and his wife.

Q. Why was the decoding of the human genome essentialfor the development of geneticmedicine?

The genome is where it starts and ends. The genome connects us to every living organism on the planet. It contains the history of the human race. The history of your family. And yet each one is unique. Not even your identical twin has the same genome (though its very similar). Decoding the genome was a monumental feat in history akin to the Moon landing. Butlittle-known factit didnt truly get finished until this year when many of the complicated regions and holes from 20 years ago got filled in.

Q. Why does genetic-based medicine provide a better approach to curing diseases thanour current models?

All diseases have a genetic component, but some diseases are mostly genetic. These are often referred to asMendelianafterthe Austrian monk Gregor Mendel,who discovered the fundamental laws of genetics while cultivating pea plants. For these Mendelian diseaseswith minimal environmental component (mostly nature, very little nurture) to understandunderstandingthe genetic basis of the disease isfinallytounderstand, at the deepest level,how the disease comes about. It also has to be the starting point of finding truly effective medicines, something we refer to as precision medicine.

Q. Are there any limits to how far genetic medicine can take us in the quest to eradicatehuman diseases?

Absolutely. For example, all diseases have an environmental component. Heart disease,for example,is half nature and half nurture. We have to pay attention to both. Also, somediseases are caused by pathogens and some by our immune system. Fortunately, for these diseases, genetic sequencingof the pathogen or the immunecellscan also be very useful.

Q. There have been numerous false starts in the field gene therapy. Do you think weshould remain cautious for now about the futureprospect of a genomic medicinerevolution?

The false starts have mostly been with genetic therapy,where the early promise of the 1990sgave way after one or two high-profile deaths to 20 yearsof introspection and hard work;a time where our community really addressed the challenges head on. As a result, we are now in a golden age of genetic therapy. We still need to be cautiousthis is powerful technologybut every day more and more diseases become susceptible to genetic approaches.

Q. Some people get worried about the advent of genetic medicine, just as some were at one time concerned about genetically-modified crops. Is there any justification for such fears?

A. I think a better way to think about genetic therapy is like a more long-lasting form of a traditional medicine. Traditional medicines reprogram towards health how our cells work from the surface or through changing signals inside the cell. They work as long as the medicine is still present. Genetic therapy, on the other hand works, at the level of the genetic code (DNA) or its messenger (RNA). So therapies can be given perhaps every few months, or even like a vaccine, just once. That is very convenient! However, it also means we have to be very careful that we have tested the process thoroughly before testing it in humans. It is important to note that genetic therapy today is not about designer babies. Our community is universally opposed to this sort of genetic modification of our inheritance line. The current therapies are delivered to certain cells in one person at a time and those changes are never passed on to future generations.

Q. How has genetic medicine been instrumental in the fight against Covid-19?

A. Genetic sequencing has been the most fundamental technology in our fight against Covid-19. All the diagnostic tests we have are based at some level on knowledge of the genome of SARS-CoV-2. Also, all the vaccines approved to date are genomic vaccines, based upon the sequence of the virus. Sequencing also allows us to track the virus and its evolution to new variants around the globe. Most importantly, sequencing the virus will allow us to prevent the next pandemic by helping us understand which pathogens are most likely to cause disease and even perhaps allowing us to develop vaccines before the diseases the pathogens might cause ever come to light.

Q. The Genome Odyssey talks of ongoing studies into genetic superhumans and how their rare genes could result in all manners of new treatments in the coming years. In some respects, it sounds similar to the rush to find new medicinal plants in the Amazon rainforest. Is that a fair comparison, and what do you think will be the fruits of these ongoing investigations, in terms of future treatments?

A. Its a great question. In so many ways, the answer to many of our medical conundrums is likely out there in the world, whether in the rainforest or in the genomes of our fellow humans. Large-scale studies where altruistic individuals share their medical and genetic data for the good of the world allow us to identify a small number who are resistant to disease. By understanding why and how they are resistant we can start to design new medications that mimic these superhuman qualities. With immune (antibody)-based and genetic-based therapies we can go from human genome to human medicine even faster than ever.

Q. Still on the topic of superhumans, do you think that we could one day all receive a simple jab that would give us the strength and stamina of an Olympic-medal athlete?

A. Well, just because something is possible doesnt mean we should do it! In reality, however, we are so far away from knowing enough about the genetics of what makes our Olympians jump higher and run faster that even if someone wanted to genetically engineer superhumans, we simply dont have the knowledge to do that. I think a much better idea is to focus on how to prevent devastating diseases and improve quality of life for everyone around the globe. Realising that some people are resistant to disease and dedicating ourselves to understanding that would be a far bigger service to humanity than making a few lucky (?) people run faster.

Q. Your book is full of incredible medical success stories that you have been involved with. If you were asked to single out just one, which one would it be, and why?

A. I think that the little baby, Astrea, whose heart stopped multiple times on the first day of her life was among the most memorable adventures Ive ever been involved in. And not just for the fact we were able to sequence and analyse her genome faster than anyone had previously donethat was just the start. It was memorable because a whole village of scientists, entrepreneurs, geneticists, cardiologists, surgeons, and computer scientists from academia and industry came together to find answers for a little baby in distress. People simply dropped what they were doing and dedicated themselves to this. It really took my breath away.

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MUST READ OF THE WEEK: THE GENOME ODYSSEY BY DR EUAN ANGUS ASHLEY - Blackpool Gazette

On May 17, NHGRI announced plans to appoint Vence Bonham Jr., J.D. as acting deputy director. Vence, who joined NHGRI in 2003, is currently senior advisor to the NHGRI director on genomics and health disparities as well as head of the Health Disparities Unit in NHGRIs Social and Behavioral Research Branch. His appointment as acting deputy director will expand on his current roles, in which he has made major contributions to the Institutes research on diversity, inclusion, and health equity. In this new role, Vence will assume a more elevated position at the Institute, helping the NHGRI leadership advance NHGRIs mission and priorities.

The NHGRI deputy director position has been vacant since Mark Guyer, Ph.D., retired in 2014. The upcoming appointment of Vence as the NHGRI acting deputy director reflects the Institutes desire to have a leader at the highest possible level to guide programmatic activities to advance work related to diversity, inclusion, and health equity at the national level, but also lead NIH and NHGRIs efforts to address anti-racism and social justice. These are significant priority areas for NHGRI, and Vences leadership will be invaluable.

One of Vences first responsibilities as acting deputy director will be to create a new Office of Workforce Diversity and Health Equity within the NHGRI Office of the Director. The new office will work towards NHGRIs goals Vence will work closely with other NHGRI leaders to develop the offices mission and vision, establish a staffing plan, and lead efforts to recruit its first director.

Vence is familiar with NHGRIs long-standing leadership on issues related to diversity in genomics. Most recently, he led the NHGRI Genomic Workforce Diversity Working Group that established an action agenda for enhancing the diversity of the genomics workforce, which was published earlier this year. Vence and NHGRIs Director, Dr. Eric Green, also co-authored a commentary in the American Journal of Human Genetics, which described the imperative to enhance the diversity of the genomics workforce for achieving the promise of genomics. In his new role, Vence will focus on implementing this action agenda and will continue to be one of three NHGRI leaders serving on key NIH-wide committees as part of the NIH UNITE Initiative, which aims to end structural racism in biomedical research.

Vence also has a long history of starting successful initiatives at NHGRI. He established the Education and Community Involvement Branch and served as its inaugural chief. The branch thrived under his leadership, including the creation of the Smithsonian-NHGRI exhibition, Genome: Unlocking Lifes Code.

His research program focuses primarily on the social implications of new scientific knowledge, particularly in communities of color. He and his group study how genomics influences the use of the constructs of race and ethnicity in biomedical research and clinical care, as well as how genomics worsens or improves health inequities. They also study sickle cell disease, a condition that is affected by emerging curative genomic technologies and that faces significant health disparities both in the US and worldwide.

Vences appointment as the NHGRI acting deputy director is anticipated to begin in early summer.

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Vence Bonham to be appointed acting NHGRI deputy director - National Human Genome Research Institute

In a new study, University of Maine researchers found that culture helps humans adapt to their environment and overcome challenges better and faster than genetics.

After conducting an extensive review of the literature and evidence of long-term human evolution, scientists Tim Waring and Zach Wood concluded that humans are experiencing a special evolutionary transition in which the importance of culture, such as learned knowledge, practices and skills, is surpassing the value of genes as the primary driver of human evolution.

Culture is an under-appreciated factor in human evolution, Waring says. Like genes, culture helps people adjust to their environment and meet the challenges of survival and reproduction. Culture, however, does so more effectively than genes because the transfer of knowledge is faster and more flexible than the inheritance of genes, according to Waring and Wood.

Culture is a stronger mechanism of adaptation for a couple of reasons, Waring says. Its faster: gene transfer occurs only once a generation, while cultural practices can be rapidly learned and frequently updated. Culture is also more flexible than genes: gene transfer is rigid and limited to the genetic information of two parents, while cultural transmission is based on flexible human learning and effectively unlimited with the ability to make use of information from peers and experts far beyond parents. As a result, cultural evolution is a stronger type of adaptation than old genetics.

Waring, an associate professor of social-ecological systems modeling, and Wood, a postdoctoral research associate with the School of Biology and Ecology, have just published their findings in a literature review in the Proceedings of the Royal Society B, the flagship biological research journal of The Royal Society in London.

This research explains why humans are such a unique species. We evolve both genetically and culturally over time, but we are slowly becoming ever more cultural and ever less genetic, Waring says.

Culture has influenced how humans survive and evolve for millenia. According to Waring and Wood, the combination of both culture and genes has fueled several key adaptations in humans such as reduced aggression, cooperative inclinations, collaborative abilities and the capacity for social learning. Increasingly, the researchers suggest, human adaptations are steered by culture, and require genes to accommodate.

Waring and Wood say culture is also special in one important way: it is strongly group-oriented. Factors like conformity, social identity and shared norms and institutions factors that have no genetic equivalent make cultural evolution very group-oriented, according to researchers. Therefore, competition between culturally organized groups propels adaptations such as new cooperative norms and social systems that help groups survive better together.

According to researchers, culturally organized groups appear to solve adaptive problems more readily than individuals, through the compounding value of social learning and cultural transmission in groups. Cultural adaptations may also occur faster in larger groups than in small ones.

With groups primarily driving culture and culture now fueling human evolution more than genetics, Waring and Wood found that evolution itself has become more group-oriented.

In the very long term, we suggest that humans are evolving from individual genetic organisms to cultural groups which function as superorganisms, similar to ant colonies and beehives, Waring says. The society as organism metaphor is not so metaphorical after all. This insight can help society better understand how individuals can fit into a well-organized and mutually beneficial system. Take the coronavirus pandemic, for example. An effective national epidemic response program is truly a national immune system, and we can therefore learn directly from how immune systems work to improve our COVID response.

Waring is a member of the Cultural Evolution Society, an international research network that studies the evolution of culture in all species. He applies cultural evolution to the study of sustainability in social-ecological systems and cooperation in organizational evolution.

Wood works in the UMaine Evolutionary Applications Laboratory managed by Michael Kinnison, a professor of evolutionary applications. His research focuses on eco-evolutionary dynamics, particularly rapid evolution during trophic cascades.

Contact: Marcus Wolf, 207.581.3721; marcus.wolf@maine.edu

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UMaine researchers: Culture drives human evolution more than genetics - UMaine News - University of Maine - University of Maine

NEW YORK Myriad Genetics unveiled data at the American Society of Clinical Oncology's virtual annual meeting demonstrating that its polygenic score for assessing breast cancer risk can provide accurate estimates for women regardless of their ancestry.

The company launched riskScore three years ago initially as a test for estimating the five-year and lifetime risk of breast cancer for women who had never had the disease and who do not have a mutation in breast cancer-associated genes detected by its next-generation sequencing myRisk Hereditary Cancer test. However, the availability of the around 86-SNP polygenic risk score to date has been restricted to women who self-identified as having European and Ashkenazi Jewish ancestry.

Now, having recalibrated riskScore to provide more accurate breast cancer risk estimates for women in the US, regardless of their genetic ancestry, Myriad is planning to launch this version of the test later this year for women who qualify for myRisk, which gauges mutations in multiple genes conferring high or moderate risk for breast cancer. In 2022, the company will offer riskScore as a standalone, direct-to-consumer (DTC) test for women who aren't eligible for the myRisk test based on their personal and family history of breast cancer.

Polygenic risk scores rely on the combinatorial power of many SNPs associated with disease risk, but these SNPs have largely been identified in genome-wide association studies done in patients of European ancestry. As such, these scores tend to overestimate disease risk and are less accurate in discerning between high- and low-risk groups in those of non-European ancestry.

For example, studies have shown that Black women have similar incidence of breast cancer compared to white women in the US. But Myriad's 86-SNP riskScore developed for women of European ancestry overestimates the breast cancer risk in Black women by nearly twofold, said Holly Pederson, who was involved in the effort to recalibrate riskScore and directs medical breast services at the Cleveland Clinic.

Myriad wanted to address this limitation within its test and has been refining riskScore in Hispanic, African American, and other racial groups for several years. Pederson presented the culmination of those efforts at ASCO's annual meeting and unveiled a new 93-SNP riskScore, re-engineered for all ancestries using data from more than 275,000 women.

The new iteration of riskScore will not only test women for 93 breast cancer-associated SNPs, but also for 56 ancestry-associated genes, in order to calculate an ancestry-specific result that corresponds to their chances of developing breast cancer in the next five years and over their lifetime. This will preclude women from having to self-report their ancestry, which can be inaccurate, especially for non-European women. "What I found during my years of seeing patients is that many patients weren't entirely sure of their ancestry, and this will no longer be a barrier for care," said Nicole Lambert, president of Myriad Genetic Laboratories.

Weighted by genetic ancestry

The 93-SNP riskScore is weighted according to 56 SNPs associated with ancestral lineage from Africa, East Asia, and Europe, the three places that account for most of the genetic diversity in the US. "There are multiple sub-clusters within each of those [continental] clusters, so using three ancestries is a simplification of the full diversity of human populations," Pederson acknowledged during her presentation at the meeting. "However, these three ancestries together should reasonably represent most of US human genetic diversity."

Data from more than 189,000 women were used to develop the score, and it was validated in data from more than 89,000 women. In these cohorts, 23 percent of women had breast cancer and around 30 percent had a first-degree relative with the disease. Roughly 10 percent of women in these cohorts self-reported as Black or African, around the same proportion self-reported as Hispanic, and around 2 percent self-reported as Asian.

To develop the score, researchers led by Myriad CSO Jerry Lanchbury and Elisha Hughes, the company's director of research biostatistics, first developed polygenic risk scores specific to people of African, Asian, and European descent using data from its own hereditary cancer testing customers with self-reported race, as well as from large consortia and genome-wide association studies. For each of the patients in the development cohort, researchers determined their "fractional ancestry" from the three continents using the 56 SNPs, which then allowed for the ancestry-adjusted calculation of their risk for developing breast cancer based on the 93 SNPs.

"The different alleles found for each SNP in an individual woman are interpreted not only as a function of her ancestral composition, but also on the frequency of that allele's presence in one of the three continental ancestries because they are each different," Pederson said. "An individual woman's polygenic risk score therefore depends not only on her genotype, but also on her ancestral derivation and the frequency of an allele in a given ancestry."

In the validation cohort, researchers wanted to see how well the re-engineered riskScore distinguished between women at high and low-risk of developing breast cancer across ancestries and how the new score compared to the 86-SNP test for women of European descent. The study showed that the 93-SNP test was generally an improvement over the 86-SNP test in terms of breast cancer risk predictions for women of all ancestries. In their abstract, the authors noted that the Asian cohort was too small to demonstrate that either score was superior.

Furthermore, the validation study showed that the women with the recalibrated riskScore placed in the highest risk category the top 1 percent in fact had a two to threefold greater chance of developing breast cancer compared to average-risk women. For women of all self-reported ancestries, except Black women, if the test placed them in the top decile in terms of risk, they were twice as likely to develop breast cancer compared to average-risk women.

Self-reported African or Black women who were deemed by riskScore to be in the top decile in terms of risk had a 44 percent greater chance of developing breast cancer risk. Pederson said during her presentation that the re-engineered riskScore's ability to assess self-reported Black women's breast cancer risk was "significantly improved" compared to the earlier test but still "sub-optimal." She added that the new score's risk discrimination in Black women will likely become more precise with additional data.

"We have known for some time that genomically-based breast cancer risk stratification was biased towards SNPs from women with European ancestry and did not perform as well in women ofother ancestries," said Corey Speers, assistant professor of radiation oncology at the University of Michigan Rogel Cancer Center. "This study represents an important step to 'level the field' for women of disparate ancestries and more accurately estimate breast cancer risk in these women," Speers, who researches the biology of aggressive breast cancers and wasn't involved in the riskScore study, added.

More definitive guidance

Cleveland Clinic, where Pederson works, hasn't yet incorporated polygenic risk scores into standard disease risk estimation workflows. The academic medical center is participating in a prospective study, called GENRE-2, using a 300-SNP breast cancer polygenic risk score developed by Fergus Couch at the Mayo Clinic. In that study, researchers are tracking if this score helps patients make decisions about breast cancer prevention, such as whether to take endocrine therapy. https://clinicaltrials.gov/ct2/show/NCT04474834?term=GENRE-2&draw=2&rank

Outside of the research setting, however, the lack of validation in non-European populations has been a big reason holding up adoption of polygenic risk scores for breast cancer and other diseases. "Clinically, the polygenic risk score is really in its infancy," Pederson said. "Previous to this, really due to concerns over applicability in non-European populations and interpretation and communication of the results, we have not utilized polygenic risk scores at Cleveland Clinic."

Even though Myriad has been offering the 86-SNP riskScore for European women as part of myRisk at no additional cost, Cleveland Clinic has been opting out of that information, according to Pederson. This study, she believes, may very well change that, since to the best of her knowledge Myriad's test is the only breast cancer polygenic risk score that has been calibrated to be informative for all ancestries.

Speers noted as a positive that the training and validation cohorts in the study presented at ASCO included tens of thousands of women and were well balanced in terms of the factors that are most likely to influence breast cancer risk. He is eagerly awaiting peer-reviewed publication of the data, upon which he expects that riskScore will represent "an important step forward for providing equitable and accurate test results for women of all ancestral backgrounds."

With the increasing use of multi-gene tests, like myRisk, which look for pathogenic variants in moderate-risk genes alongside well-known high-risk genes like BRCA1/2, more patients are receiving results where the management implications aren't well established. This can be particularly difficult when women's personal or family history of cancer doesn't offer straightforward clues as to their future cancer risks.

Myriad and others developing polygenic risk scores are betting that these tests will providerisk information when large NGS panels turn up negative or even refine risk estimates when considered alongside mutations in moderate-penetrance genes, and relieve uncertainties around patient management. "If patients have a genetic mutation in CHEK2, which is a moderate-risk gene, we tell them they have an estimated lifetime [breast cancer] risk of about 30 percent," Pederson said. "But when you look at the risk stratification that can be achieved by a polygenic risk score, patients may have a risk as low as 6.6 percent over the course of her life or a 70 percent risk, which is similar to a patient with a BRCA1/2 [high-risk] mutation."

Women she treats overwhelmingly want to know this information, Pederson said.

Although she believes that Myriad's new riskScore is "sufficiently validated and calibrated" in all ancestries, she would like to see the test factor in patients' clinical features that also increase their chances of developing breast cancer. At her own practice, patients' decisions about having preventive mastectomies or oophorectomies to mitigate their cancer risk isn't just based on genetic testing but also on a variety of other clinical factors, as well as patients' own priorities for their health and family planning.

The genetic test result is "just one piece of information," she said. "While it is useful in and of itself, it'll be even more useful for a woman to get an estimate in combination with those other [clinical] factors. It just allows for more precise estimates and better conversations."

Myriad's 86-SNP score for European women incorporates the Tyrer-Cuzick risk model, which evaluates breast cancer risk based on features like age, body mass index, age of first period, and family history of cancer. Myriad is working on integrating clinical risk features into the recalibrated riskScore, Pederson said, adding that this work will likely be presented at a medical meeting by year end.

Access to all

Myriad is planning to launch the recalibrated riskScore for all ancestries later this year, but in the near-term will maintain it as a physician-ordered test offered alongside myRisk. Next year, however, the company wants to launch riskScore as a standalone test through a DTC model for the estimated 93 million women who don't qualify for testing for high- or moderate-penetrance breast cancer risk genes based on stringent personal and family cancer history criteria, as well as the National Comprehensive Cancer Network's guidelines. "This will allow us to provide a precise risk estimate to all women: myRisk for those who qualify, standalone riskScore for those who dont," said Lambert.

Myriad's DTC plans for riskScore also raises questions about how the company will navigate the regulatory landscape. The US Food and Drug Administration has been clear about its intent to regulate labs marketing genetic tests for assessing disease risk directly to consumers.

23andMe is the only company that currently sells FDA-authorized genetic tests for gauging disease risk, including for cancer, which people can order online without any physician involvement. Other companies offering testing in CLIA-certified labs have found ways around FDA oversight by using third-party physician networks to review and approve customer's online orders. However, this is a controversial model because often the physicians approving test orders don't have much interaction with the patients.

Myriad demurred on its specific regulatory plans, saying that it is still ironing out the specific DTC model it will employ when it launches riskScore as a standalone test next year. "We are currently assessing the regulatory requirements, talking with stakeholders, and creating the specific launch plans," Lambert said.

Pederson backed efforts to broaden access to cancer risk testing, recognizing that using current testing guidelines, largely based on personal and family history of cancer, the healthcare system has identified only a minority of patients with mutations in high-risk genes. At the same time, the rapid introduction of broad NGS panels has made it difficult for physicians lacking genetic expertise to accurately interpret test reports.

As such, a broad marketing strategy for polygenic risk scores must include a robust education plan for patients and providers, Pederson said, including genetic counseling support and resources to help primary care providers interpret test reports and relay nuanced risk information to patients.

Lambert assured that Myriad currently makes genetic counselors available to any doctor or patient ordering germline genetic testing and that these resources would also be available in the consumer-facing service. "We are in the process of evaluating what other services would be desirable as we prepare for the launch of the consumer version in 2022," she said.

Ultimately, given the popularity of DTC genetic testing, "something real like this, if it is priced right and marketed correctly, would really provide women with information that they really want," Pederson said.

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Myriad Genetics Recalibrates Breast Cancer PRS for All Ancestries in Anticipation of Broader Launch - Precision Oncology News

Sergi Beltran and Leslie Matalonga pictured in front of a supercomputer and servers that hosts the RD-Connect GPAP platform. The platform is located at the CNAG-CRG facilities in the Parc Cientific de Barcelona. Credit: Centro Nacional de Anlisis Genmico (CNAG-CRG)

Rare disease experts detail the first results of an unprecedented collaboration to diagnose people living with unsolved cases of rare diseases across Europe. The findings are published today in a series of six papers in theEuropean Journal of Human Genetics.

In the main publication, an international consortium, known as Solve-RD, explains how the periodic reanalysis of genomic and phenotypic information from people living with a rare disease can boost the chance of diagnosis when combined with data sharing across European borders on a massive scale. Using this new approach, a preliminary reanalysis of data from 8,393 individuals resulted in 255 new diagnoses, some with atypical manifestations of known diseases.

A complementary study describes the method in more detail and four accompanying case studies showcase the advantages of the approach. In one case study, researchers used the method to identify a new genetic form of pontocerebellar hypoplasia type 1 (PCH1), a genetic disease that affects the development of the brain. PCH1 is normally linked to mutations in four known genes. The researchers used the method to identify a new variant in a fifth gene.

In another case study, researchers used the method on an individual with a complex neurodevelopmental disorder and found the disease was caused by a new genetic variant in mitochondrial DNA. This went previously undetected because the patient did not present typical symptoms of a mitochondrial disorder. The diagnosis will help tailor treatment for the individual, as well as inform their family members on the possibility of passing it on to future generations.

Key to the reanalysis of unsolved cases is theRD-Connect Genome-Phenome Analysis Platform, which is developed, hosted and coordinated by the Centro Nacional de Analisis Genomico (CNAG-CRG), part of the Centre for Genomic Regulation (CRG), based in Barcelona.

Recognized officially by the International Rare Diseases Research Consortium and funded by the EU, Spanish and Catalan governments, the RD-Connect GPAP provides authorised clinicians and researchers with secure and controlled access to pseudonymized genomic data and clinical information from patients with rare diseases. The platform enables the secure, fast and cost-effective automated re-analysis of the thousands of undiagnosed patients and relatives entering the Solve-RD project.

According to Sergi Beltran, co-leader of Solve-RD data analysis and Head of the Bioinformatics Unit at CNAG-CRG, Solve-RD has shown that it is possible to securely share large amounts of genomics data internationally for the benefit of the patients. The work we are publishing today is just the tip of the iceberg, since many more patients are being diagnosed thanks to the innovative methods developed and applied within Solve-RD.

An estimated 30 million people in Europe are affected by a rare disease during their lifetime. More than 70% of rare diseases have a genetic cause. However, around 50% of patients with a rare disease remain undiagnosed even in advanced expert clinical settings that use techniques such as genome sequencing.

At the same time, scientists around the world are finding an average of 250 new gene-disease associations and 9,200 variant-disease associations per year. As scientific understanding expands, reanalyzing data periodically can help people receive a diagnosis.

The consortium, which consists of more than 300 researchers and clinicians in fifteen countries, and who collectively see more than 270,000 rare disease patients each year, aims to eventually diagnose more than 19,000 unsolved cases of rare diseases with an unknown molecular cause. Their preliminary findings are an important first step for the development of a European-wide system to facilitate the diagnosis rare diseases, which can be a long and arduous process.

About Solve-RD

Solve-RD solving the unsolved rare diseases is a research project funded by the European Commission for five years (2018-2022). The consortium, which consists of 21 European academic institutions and 1 academic partner from the United States, is jointly coordinated by the University of Tbingen in Germany, Radboud University Medical Centre in the Netherlands and the University of Leicester in the UK. The Centro Nacional de Anlisis Genmico (CNAG-CRG) in Barcelona is the main partner in Spain.

About CNAG-CRG

The Centro Nacional de Anlisis Genmico is one of the largest European centers in terms of sequencing capacity. It was created in 2009 with the mission to carry out projects in nucleic acid analysis in collaboration with the national and international research community. It is a non-profit organization funded by the Spanish Ministry of Economy and Competitiveness, and the Catalan Government through the Economy and Knowledge Department and the Health Department. Since 2015 it is part of the Centre for Genomic Regulation (CRG).

The center focuses on sequencing and analysis projects in areas such as cancer genetics, rare disorders, host-pathogen interactions, de novo assembly and genome annotation, evolutionary studies and improvement of species of agricultural interest, in collaboration with universities, hospitals, research centers and companies in the sector of biotechnology and pharma.

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Unprecedented Data Sharing Drives New Rare Disease Diagnoses Just Tip of the Iceberg - SciTechDaily

THOUSAND OAKS, Calif., June 4, 2021 /PRNewswire/ -- Amgen (NASDAQ:AMGN) will present at the Goldman Sachs 42nd Annual Global Healthcare Conference at 4:40 p.m. ET on Wednesday, June 9, 2021. David M. Reese, M.D., executive vice president of Research and Development and Peter H. Griffith, executive vice president and chief financial officer at Amgen will present at the conference. Live audio of the conference call will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

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

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

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

For more information, visit http://www.amgen.com and follow us on http://www.twitter.com/amgen.

CONTACT: Amgen, Thousand Oaks Megan Fox, 805-447-1423 (media)Michael Strapazon, 805-313-5553 (media) Arvind Sood, 805-447-1060 (investors)

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