American Society of Human Genetics
American Society of Human Genetics
News Article | April 26, 2017
Each year in honor of National DNA Day, celebrated April 25, the American Society of Human Genetics (ASHG) hosts an essay contest that aims to inspire high school students to delve deeper into human genetics concepts than the standard curriculum and flex their creativity by writing original essays. This year the essay topic asked students to pick one example of gene therapy since 2005, explain the disease scientists are trying to treat, and describe how the therapy or technique might address the underlying cause of the condition. “Recent advances in biology have made gene therapy, the focus of this year’s contest, more promising than ever, and have expanded the field beyond its original concept,” Michael Dougherty, Ph.D., Director of Education for ASHG said in a prepared statement. “We were interested to see students’ perspectives on these advances and their potential effects in the clinic.” Entries were submitted from 38 U.S. states and 21 international countries this year. The essays were evaluated by human genetics experts belonging to ASHG and were critiqued based on three factors: scientific accuracy, creativity and overall writing. Here are this year’s top three winners: In addition, 11 students were awarded honorable mentions and will each receive a $100 prize. Grants for genetics laboratory equipment are also awarded to eligible teachers. “This year’s essays continue the tradition of high-quality submissions by high school students from the U.S. and abroad that we have seen for the past 12 years, and their enthusiasm for science reflects the excitement that our members feel about their work,” Joseph D. McInerney, Executive Vice President of ASHG said in a statement. “Through this contest and our other K-12 initiatives, we hope to encourage young people to explore and enjoy genetics.” National DNA Day commemorates the discovery of the double helix of DNA in 1953 as well as the completion of the Human Genome Project in April 2003. To see the 11 honorable mentions and learn more about the contest winners, including excerpts from winning essays, click here.
News Article | April 26, 2017
The Howard Hughes Medical Institute's (HHMI) Medical Research Fellows Program has selected 79 talented medical and veterinary students to conduct in-depth, mentored biomedical research. Fifty-three percent of the awardees are female, the greatest representation of women in the program to date. Starting this summer, each fellow will spend a year pursuing basic, translational, or applied biomedical research at one of 32 academic or nonprofit research institutions across the United States. "The Med Fellows Program allows exceptional MD, DVM, and DDS students to effectively shift course and conduct rigorous research at top institutions throughout the country," says David Asai, senior director in science education at HHMI. "It's an extraordinary opportunity for future physicians, veterinarians, and dentists to explore the intersection of medicine and scientific discovery, and we hope that each student comes away further empowered to pursue a career as a physician-scientist." Now, 28 years after the Med Fellows Program was first launched, it has helped more than 1,700 medical, veterinary, and dental students establish a foothold in the research world. In this year's group, 18% of the fellows are from minority groups typically underrepresented in the biomedical sciences, and seven fellows will continue their research for another year. Tolu Rosanwo, a second-year fellow and medical student at Case Western Reserve University School of Medicine, says the program is a gift, but for Rosanwo, it was a gift that left her wanting more. "I couldn't leave just as my research was starting to show promise," she says. "I'm still intrigued by my initial question, and I want to see it through." That initial question dates back to Rosanwo's childhood, growing up with two siblings with sickle cell anemia. Her curiosity about what caused them to be sick turned into a committed desire to understand and contribute to a treatment for the disorder. Now, in the laboratory of George Daley, Dean of Harvard Medical School and an alumnus of the HHMI Investigator Program, she's trying to tackle that question. "An important and profound place to be is in between science and patients," she says. "I want to be a physician whose patient care is informed by research, and vice versa." Anna Cheng, a first-year fellow and current medical student at University of South Florida Morsani College of Medicine, started dabbling in the scientific method as a high school student. Science had always interested her, but when her best friend and her godmother found themselves in a fight against cancer, Cheng decided to narrow her scientific focus. "My best friend was diagnosed with leukemia and my godmother with ovarian cancer. I wanted to understand why - to figure it out," she says. "Yes, I was interested in cancer research, but I had personal factors that really drove me." During her undergraduate studies at Duke University, Cheng continued to make time for lab research, fitting it in over summers and in between coursework. And though she valued the experiences, the fleeting glimpses of bench time only whet her appetite for more. The Med Fellows Program, she says, provided her the opportunity for more sustained exposure to research. "I feel so fortunate, because now I get to pursue a project for an entire year," she says. After a thoughtful pause, she amends her statement. "But the program's experience isn't really just a year. It's something that will serve me well for the rest of my career." The Med Fellows Program takes a multilevel mentoring approach to help incoming fellows get off to a strong start, make new connections, and access a network of support throughout their fellowship year. Various meetings bring the fellows together to connect with newly minted Med Fellow alumni, early-career faculty, and senior investigators to participate in seminars and learn from physician-scientists at various career stages. The most direct form of support comes from each fellow's mentor. Cathy Wu, an alumna from the early days of the Med Fellows Program and associate professor at the Dana-Farber Cancer Institute, will be mentoring her third med fellow this fall. "The fellows are such a terrific bunch - they're brimming with enthusiasm, super smart, and eager to learn," Wu says. As someone who took great inspiration from her own mentors as a student in the program, Wu emphasizes that the mentor-mentee relationship is a crucial part in learning how to approach investigation. "Part of the Med Fellows Program is getting a sense of the opportunities and resources available - having the latitude to explore and learn about the investigative process. When I was a fellow, the program helped me cement research as part of my medical career," she says. "I'm eager for these students to have their year, too." In collaboration with HHMI, five partners - the American Society of Human Genetics, Burroughs Wellcome Fund, Citizens United for Research in Epilepsy, Foundation Fighting Blindness, and Parkinson's Foundation - will fund 8 of the 79 aspiring physician- and veterinarian- scientists, bringing the program's total investment to $3.4 million. The Howard Hughes Medical Institute plays an important role in advancing scientific research and education in the United States. Its scientists, located across the country and around the world, have made important discoveries that advance both human health and our fundamental understanding of biology. The Institute also aims to transform science education into a creative, interdisciplinary endeavor that reflects the excitement of real research. HHMI's headquarters are located in Chevy Chase, Maryland, just outside Washington, D.C.
News Article | October 12, 2016
Lurking in the genes of the average person are about 54 mutations that look as if they should sicken or even kill their bearer. But they don't. Sonia Vallabh hoped that D178N was one such mutation. In 2010, Vallabh had watched her mother die from a mysterious illness called fatal familial insomnia, in which misfolded prion proteins cluster together and destroy the brain. The following year, Sonia was tested and found that she had a copy of the prion-protein gene, PRNP, with the same genetic glitch — D178N — that had probably caused her mother's illness. It was a veritable death sentence: the average age of onset is 50, and the disease progresses quickly. But it was not a sentence that Vallabh, then 26, was going to accept without a fight. So she and her husband, Eric Minikel, quit their respective careers in law and transportation consulting to become graduate students in biology. They aimed to learn everything they could about fatal familial insomnia and what, if anything, might be done to stop it. One of the most important tasks was to determine whether or not the D178N mutation definitively caused the disease. Few would have thought to ask such a question in years past, but medical genetics has been going through a bit of soul-searching. The fast pace of genomic research since the start of the twenty-first century has packed the literature with thousands of gene mutations associated with disease and disability. Many such associations are solid, but scores of mutations once suggested to be dangerous or even lethal are turning out to be innocuous. These sheep in wolves' clothing are being unmasked thanks to one of the largest genetics studies ever conducted: the Exome Aggregation Consortium, or ExAC. ExAC is a simple idea. It combines sequences for the protein-coding region of the genome — the exome — from more than 60,000 people into one database, allowing scientists to compare them and understand how variable they are. But the resource is having tremendous impacts in biomedical research. As well as helping scientists to toss out spurious disease–gene links, it is generating new discoveries. By looking more closely at the frequency of mutations in different populations, researchers can gain insight into what many genes do and how their protein products function. ExAC has turned human genetics upside down, says geneticist David Goldstein of Columbia University in New York City. Instead of starting with a disease or trait and working backwards to find its genetic underpinnings, researchers can start with mutations that look like they should have an interesting effect and investigate what might be happening in the people who harbour them. “This really is a new way of working,” he says. ExAC is also providing better information for families facing genetic diagnoses. D178N, for example, was strongly suspected of causing prion disease because it had been seen in several people with the condition and seldom elsewhere. But before ExAC, no one really had the power to see just how rare it was. If it shows up in people more frequently than prion disease does, that would mean Vallabh's risk of getting the disease is much lower than predicted. “We needed to find out if this mutation had ever been seen in a healthy population,” Minikel says. ExAC was born of frustration. In 2012, geneticist Daniel MacArthur was starting his first laboratory, at Massachusetts General Hospital (MGH) in Boston. He wanted to find genetic mutations that caused rare muscle diseases, and needed two things: genome sequences from people with these disorders, and genome sequences from people without them. If a mutation was more common in people with a disorder than in healthy controls, it stood to reason that the mutation was a likely cause. The problem was that MacArthur couldn't find enough sequences from unaffected people. He needed lots of exomes, and although researchers had been sequencing them by the thousands, existing data sets weren't large enough. No one had pulled enough together into one combined, standardized resource. So MacArthur started asking his colleagues to share their data with him. He was well suited to the task: an early adopter of social media, his lively blog posts and acerbic Twitter feed had made him unusually popular and authoritative for a young scientist. He also had a position with the Broad Institute in Cambridge, Massachusetts, a genome-sequencing powerhouse. MacArthur convinced researchers to share data from tens of thousands of exomes with him; most were in some way connected to the Broad. All that remained was to analyse the data, but that was no trivial task. Although the genes had been sequenced, the raw data had been analysed using different types of software — including some that were out of date. If one individual in the collection showed a rare mutation, it could be real — or it could be an artefact of how different programs 'called' the bases within, judging whether they were As, Cs, Ts or Gs. MacArthur needed something that would standardize this gigantic data set. The Broad had developed genome-calling software, but it wasn't up to the task of churning through the tremendous amount of data included in ExAC. So MacArthur's team worked closely with the Broad programmers to test the software and scale up its abilities. “That was a pretty horrific 18 months,” MacArthur recalls. “We ran into every obstacle imaginable and had nothing to show for it.” While this was going on, in April 2013, Vallabh was learning how to work with stem cells at MGH while Minikel studied bioinformatics. Minikel met MacArthur for lunch and explained his and Vallabh's curiosity about whether D178N existed in healthy people. He admits to being a bit star-struck by MacArthur's reputation. “I thought if I could get him to think about my problem for half an hour, that would probably be the most important thing that happened in my whole month,” Minikel says. The pair went upstairs to MacArthur's lab, where bioinformatician Monkol Lek ran a search on the ExAC data that had been analysed so far — about 20,000 exomes. They didn't see Vallabh's mutation. That wasn't good news, but, optimistic about exploring the data further, Minikel joined MacArthur's lab. By June 2014, MacArthur's team and its collaborators had a data set that they were confident in — exomes from 60,706 individuals representing various ethnic groups, who met certain thresholds for health and consent. They released ExAC that October at the annual meeting of the American Society of Human Genetics (ASHG), in San Diego, California. Immediately, researchers and physicians recognized that the data could help to recast their understanding of genetic risks. Many disease-association studies, particularly in recent years, have identified mutations as pathogenic simply because scientists performing analyses on a group of people with a disorder found mutations that looked like the culprit, but didn't see them in healthy people. But it's possible that they weren't looking hard enough, or in the right populations. Baseline 'healthy' genetic data has tended to come mainly from people of European descent, which can skew results. In August this year, MacArthur's group published1 its analysis of ExAC data in Nature, revealing that many mutations thought to be harmful are probably not. In one analysis, the group identified 192 variants that had previously been thought to be pathogenic, but turned out to be relatively common. The scientists reviewed papers about these variants, looking for plausible evidence that they actually caused disease, but could find solid evidence for only nine of them. Most are actually benign, according to standards set by the American College of Medical Genetics and Genomics, and many have now been reclassified as such. Similar work promises to have direct impacts on medical practice. In a companion paper2, geneticist Hugh Watkins of the University of Oxford, UK, looked at genes associated with certain types of cardiomyopathy that cause gradual weakening of the heart muscle. Undetected, they can lead to sudden death, and it has become fairly common to check relatives of people with the conditions for genetic mutations associated with them. Those found to have a genetic risk are sometimes counselled to get an implanted defibrillator, which delivers electrical shocks to the heart if it seems to be beating abnormally. Watkins checked the ExAC database for information on genes that have been associated with these heart conditions, and found that many mutations are much too common among healthy people to be pathogenic. About 60 genes had been implicated as harbouring pathogenic mutations that cause one form of the disease; Watkins' analysis revealed that 40 of these probably bear no link. This was troubling. “If you have a genetic risk that you believe is predicting disease but isn't, you can end up doing drastic things that can harm someone,” says Watkins. Even some of the mutations that seem to be reliably linked to disease aren't a sure bet — such as those in PRNP. There are definitely mutations in the gene that cause the disease, but some variants might not be pathogenic or might elevate the risk only slightly (see 'The deadly mutations that weren't'). To find out the status of D178N, Vallabh and Minikel gathered genetic data from more than 16,000 people who had been diagnosed with prion diseases, and compared them with data from almost 600,000 others, including the ExAC participants3. The pair found that 52 people in ExAC had PRNP mutations that have been linked to prion diseases, but based on the prevalence of the disease, they would have expected to see maybe two. Minikel calculated that some of these supposedly lethal mutations elevated a person's risk of prion disease slightly; some seemed not to be linked to prion disease at all. This work provided insight for people such as Alice Uflacker. In 2011, Uflacker's father, Renan, died from Creutzfeldt–Jakob disease, a prion illness that causes rapid mental and physical deterioration. He was 62. Alice found out that she carried a mutation in PRNP called V210I, which had been linked to her father's disease in previous studies. Three years later, she learned from Minikel that the mutation confers, at most, a small risk of disease. The information was helpful, and the result made sense; her grandmother had lived to 93 despite having the same mutation. Vallabh and Minikel would find no such relief, however. D178N was absent from the other genomes they looked at, and is still highly likely to cause prion disease. Minikel and Vallabh had already begun to suspect as much, as Minikel dug into the data. “All along the way was gradual confirmation of what we were assuming anyway,” Minikel says. “There wasn't any moment where we said, 'Ah, this is the worst news.' We'd already gotten the worst news.” ExAC is revealing a lot about genes through the frequency of mutations. MacArthur and his team found1 3,200 genes that are almost never severely mutated in any of the ExAC genomes — a signal that these genes are important. And yet 72% of them have never before been linked to disease. Researchers are eager to study whether some of these genes play unappreciated parts in illness. Conversely, the group has found nearly 180,000 instances of mutations so severe that they should render their protein products completely inactive. Scientists have long studied genes by knocking them out in animals such as mice, so that they don't work. By looking at the symptoms that develop, they can study what the genes do. But that has never been possible in humans. Now, researchers are eager to study these natural human knockouts to understand what they can reveal about how diseases develop or may be cured. MacArthur and other researchers are gearing up to prioritize which human knockout genes to study and how best to contact the people carrying them for further study. But it will have to wait until he completes the second phase of ExAC. Due to be unveiled at the ASHG meeting in Vancouver, Canada, this month, it will double the data set's size to 135,000 exomes and include some 15,000 whole-genome sequences, which should allow researchers to explore mutations in regulatory regions of the genome that are not captured by exome sequencing. ExAC is quietly becoming a standard tool in medical genetics. Clinical labs around the world now check it before telling a patient that a particular glitch in their genome might be making them ill. If the mutation is common in ExAC, it's unlikely to be harmful. Geneticist Leslie Biesecker at the US National Human Genome Research Institute in Bethesda, Maryland, says that his lab uses ExAC daily in patient care. “It's a critical factor that we take into consideration for every variant,” he says. He and other geneticists are now embarking on a painstaking reckoning with the genetics literature that will probably take years. ExAC has also driven home a point that Goldstein and other researchers have made repeatedly: that failing to include people from Asian, African, Latino and other non-European ancestries is holding back understanding of how genes influence disease by limiting the view of human genetic diversity. There is now a fresh impetus to include under-represented groups in planned studies linking genetics and health information on large numbers of people, such as the US Precision Medicine Initiative. For Vallabh and Minikel, ExAC provided a disheartening confirmation, but also some promising insight. Minikel's studies have identified3 three people in ExAC with mutations that should silence one of the two copies of the prion protein gene. If they can live with a limited amount of functioning protein, perhaps a drug could be made that would silence the defective protein in Vallabh, preventing prion aggregation and disease progression without dangerous side effects. Minikel got in touch with one of the individuals, a man in Sweden, who agreed to donate some cells for research. Minikel and Vallabh have now joined the lab of biochemist Stuart Schreiber at the Broad Institute, where they are working full-time to find candidate drugs to treat prion disease. The couple exemplifies the challenge of translating ExAC data into real medical benefits. “We can't go back from this,” Vallabh says. “We have to go through it.” Their situation couldn't be more illustrative of what is at stake: Vallabh is now 32 — just 20 years younger than her mother was when she died. She has no time to waste.
News Article | November 3, 2016
DETROIT - Scientists at the Wayne State University School of Medicine's Center for Molecular Medicine and Genetics have shown for the first time the extent by which interactions between environmental exposures and genetic variation across individuals have a significant impact on human traits and diseases like diabetes, heart disease and obesity, strengthening the case for precision medicine initiatives. The discovery is particularly important when considering communities with different ancestries sharing the same risk environment -- the case for many urban communities, including Detroit, the researchers said. Generally, people may share the same genetic risk factors but their chances to develop a disease are increased by specific environmental exposures. Human environments are difficult to measure, especially when trying to study these complex interactions. For example, the researchers explained, it is hard to quantify the amount of stress in a person's life or the caffeine or vitamin content in their diets. "Both genes and environmental conditions are major influences on our health and who we are. For example, stress is a risk factor for cardiovascular disease; however, the actual risk to have a heart attack depends not only on the amount of stress in a person's life but also on the specific DNA sequences -- genetic variants -- that he or she inherited from their parents," said researcher Francesca Luca, Ph.D., who led the study with co-principal investigator Roger Pique-Regi, Ph.D. "The interplay between genetic variants and environments during human evolutionary history provided the driving force that shaped our genome. Today, genetic adaptations that helped us in the past to better store energy in fat, for example, can make us more likely to develop a disease like diabetes or obesity." Luca and Pique-Regi are assistant professors of molecular medicine and genetics, and of obstetrics and gynecology, and have spent three years working on the project with a dedicated team of collaborators that included several WSU students and postdoctoral fellows, including recent graduate Gregory Moyerbrailean, Ph.D.; graduate student Cynthia Kalita; postdoctoral fellow Allison Richards, Ph.D.; and third-year medical student Daniel Kurtz. Studying the interaction between genetic variants and environment is an incredibly complex problem to tackle at the organismal level. The WSU-based team explored, at the molecular level, gene expression changes across 250 different cellular environments, including caffeine, vitamins, metal ions, hormones, contaminants and common drugs. "Our cellular system simplifies the complexity of the environment, and allows us to develop robust statistical tests to identify 215 genes with an activity modulated by genetic variants that interact with our controlled environmental perturbations," Luca said. "Surprisingly, 50 percent of these interactions are in genes important for human traits and diseases. For example, one of these interactions in the GIPR gene suggests that caffeine intake in the presence of a genetic protective factor may decrease the risk to develop obesity. Similarly, low selenium intake, in the presence of a genetic risk factor in the LAMP3 gene, may further increase the risk for Parkinson's disease." This is the first time that large-scale genomic experiments have shown that an individual's personal environment and genetic makeup can directly affect and influence their health. The results of the project are presented in the open-access Genome Research article "High-throughput allele-specific expression across 250 environmental conditions," published last month. In addition to the Genome Research publication, the researchers presented two talks on their work at October's American Society of Human Genetics in Vancouver. The research team is now investigating the precise molecular mechanisms of the interactions, exploring additional environmental exposures -- including the human microbiome -- and performing similar studies in a large number of individuals of African American origin to explore a larger number of genetic variants. The work was supported by grants from the National Institutes of Health (R01 GM109215) and the American Heart Association. Founded in 1868, the Wayne State University School of Medicine educates more than 1,000 medical students in all four classes. In addition to undergraduate medical education, the school offers master's degree, Ph.D. and M.D./Ph.D. programs in 14 areas of basic science to about 400 students annually. Wayne State University is a premier urban research institution offering more than 380 academic programs through 13 schools and colleges to more than 27,000 students.
News Article | March 2, 2017
BIRMINGHAM, AL, March 02, 2017-- Dr. Wayne Finley has been included in Marquis Who's Who. As in all Marquis Who's Who biographical volumes, individuals profiled are selected on the basis of current reference value. Factors such as position, noteworthy accomplishments, visibility, and prominence in a field are all taken into account during the selection process.A medical educator with more than six decades of experience, Dr. Finley is highly regarded for mentoring, inspiring, and motivating emerging physicians and graduate students so that they are set up for success at the start of their careers. Retired since 1996, he concluded his career with the University of Alabama School of Medicine, where he dedicated more than 36 years in a variety of roles, serving as Professor; Epidemiology and Public Health; and Chairman of Faculty Council. Certified by the American Board of Medical Genetics and Genomics, Dr. Finley served on the genetic counseling committee of the Children's Bureau of the U.S. Department HEW and on the National Research Resources Council of the National Institute of Health. He was a senior scientist for the Comprehensive Cancer Center and the Cystic Fibrosis Research Center at the University of Alabama at Birmingham (UAB). In recognition of his professional excellence, Dr. Finley was recognized by the Distinguished Faculty Lecturer Award, endowment of the Sara C. and Wayne H. Finley Chair in Medical Genetics, and renaming the Reynolds-Finley Historical Library and Annual Lecture by the UAB. He received community awards including the Lifetime Achievement Award from the Birmingham Business Journal. Named to the Alabama Healthcare Hall of Fame and presented the President's Medal by UAB, Dr. Finley was also honorably selected for inclusion into Who's Who in America, Who's Who in American Education, Who's Who in Medicine and Healthcare, Who's Who in Science and Engineering, and Who's Who in the South and Southwest.Before establishing his career in medicine, Dr. Finley served his country as a member of the U.S. Army Infantry in Germany in 1946 and later in the Army Chemical Corps and ultimately achieved the rank of Lieutenant Colonel in the Reserves. After his service, he attended Jacksonville State University, where he earned a Bachelor of Science in 1948, and the University of Alabama, where he achieved a Master of Arts in 1950, a Master of Science in 1955, a Ph.D. in 1958, and an MD in 1960. A fellow of the American College of Medical Genetics and Genomics, Dr. Finley remained at the top of his field through his memberships in American Medical Association, American Association for the Advancement of Science, New York Academy of Sciences, Society for Experimental Biology and Medicine, American Institute of Chemists, American Federation for Clinical Research, American College of Medical Genetics and Genomics, American Society of Human Genetics, the Southern Medical Association, Medical Association of the State of Alabama, and Jefferson County Medical Society. As he looks to the future, Dr. Finley intends to enjoy his retirement while taking on select consulting projects as they arise.About Marquis Who's Who :Since 1899, when A. N. Marquis printed the First Edition of Who's Who in America , Marquis Who's Who has chronicled the lives of the most accomplished individuals and innovators from every significant field of endeavor, including politics, business, medicine, law, education, art, religion and entertainment. Today, Who's Who in America remains an essential biographical source for thousands of researchers, journalists, librarians and executive search firms around the world. Marquis publications may be visited at the official Marquis Who's Who website at www.marquiswhoswho.com
News Article | December 28, 2016
The first humans venturing onto the Tibetan Plateau, often called the “roof of the world,” faced one of the most brutal environments our species can endure. At an average elevation of over 4,500 meters, it is a cold and arid place with half the oxygen present at sea level. Science has long held that humans did not set foot in this alien place until 15,000 years ago, as suggested by archaeological evidence of the earliest known settlement on the northeastern fringe of the plateau 3,000 meters above sea level. But now new genetic data indicate this may have occurred much earlier—possibly as far back as the last ice age, 62,000 years ago. A better understanding of modern Tibetans’ genetic mix and diversity could help reconstruct the history of migration and population expansion in the region, and may help unravel the mystery of the ethnic origins of Tibetans—and of how humans have adapted to low-oxygen conditions at high altitudes. For the new study, researchers sequenced the entire genomes of 38 ethnic Tibetans and 39 Han Chinese (the country’s majority ethnic group), and compared the results with published genomic sequences of other ethnic groups around the world—information that allowed the team to pinpoint the common genetic origin of different populations and to get a better grasp on the history of migration in Tibet. “Tibetan-specific DNA sequences can be traced back to ancestors 62,000-38,000 years ago…This represents the earliest colonization of the Tibetan Plateau,” says Shuhua Xu, a population geneticist at the Chinese Institute of Sciences’ Shanghai Institutes for Biological Sciences. Xu’s work was published in September in the American Journal of Human Genetics, and presented at the American Society of Human Genetics’ annual meeting in Vancouver. Since that initial migration, as the ice age tightened its grip on the plateau, genetic mixing between Tibetans and non-Tibetans probably ground to a halt for tens of thousands of years—suggesting that movement into Tibet dropped to the minimum. “The migration routes were probably cut off by ice sheets,” Xu says. “It’s simply too harsh even for the toughest hunter-gatherers.” But about 15,000 to 9,000 years ago—after the so-called last glacial maximum (LGM), during which the Earth’s ice cover had reached its most extensive point and climate was at its harshest—people flocked into Tibet en masse. “It’s the most significant wave of migration that shaped the modern Tibetan gene pool,” Xu says. “We can really see rapid population expansion [on the plateau] during that time.” Interestingly, he adds, this was also when the common ancestor of Tibetans and Han Chinese split—contrary to a previous study suggesting that the divergence took place as late as 2,750 years ago. “This is the first study to sequence the entire genome of Tibetans, and the resolution is really impressive,” says Mark Aldenderfer, an archaeologist at the University of California, Merced, who was not involved in Xu’s study. The much earlier divergence between Tibetans and Han Chinese makes sense because there are continuous material cultures on the plateau since 15,000 years ago, he says. The study, Aldenderfer adds, “also provides fine details of how different populations from various directions may have combined their genes to ultimately create the people that we call Tibetans.” The data show that 94 percent of the present-day Tibetan genetic makeup came from modern humans—possibly those who ventured into Tibet in the second wave of migration—and the rest came from archaic hominins such as Denisovans, Neandertals and unknown groups. The modern part of the Tibetan genome shares 82 percent similarity with East Asians, 11 percent with Central Asians, and 6 percent with South Asians. “Among all ethic groups, Han Chinese are most closely related to Tibetans,” Xu says. The findings also reveal a startling genetic continuity since the plateau was first colonized 62,000 years ago. “This suggests that Tibet has always been populated—even during the toughest times as far as climate was concerned,” Xu says. That idea contradicts the commonly held notion that any early plateau dwellers would have been eliminated during harsh climate intervals such as LGM and another period known as the Younger Dryas between 12,900 and 11,600 years ago, says David Zhang, a geographer at the University of Hong Kong, who was not involved in Xu’s research. In 2002 Zhang and a colleague published a controversial study in Geophysical Review Letters showing marks of hands and feet from at least six individuals in rocks that were once soft mud, which was dated to 20,000 years ago at 4,000 meters above sea level in the heart of Tibet. Based on this they theorized that people were living in Tibet at the height of LGM, but the lack of archaeological finds near the site has cast doubt on this. “Many people don’t think it’s possible,” Aldenderfer says. “But there were plenty of places for [those early populations] to live where local conditions weren’t that bad, such as the big river valleys on the plateau.” The handprints and footprints were uncovered near one of the plateau’s many hot springs, which could have served as refuges for plants, animals and humans, he adds. Two independent archaeological studies presented at the 33rd International Geographical Congress, held in August in Beijing, also support the antiquity of Tibet settlement as suggested by Xu’s genetic data. A team led by archaeologist Guanghui Dong of Lanzhou University in Gansu province unveiled the earliest archaeological evidence of human presence—dating to 39,000-31,000 years ago—on the southeastern fringe of the Tibetan Plateau. The site, rich with stone tools and animal bones, lies at 2,500 meters above sea level at the bank of the Salween River. “This may represent one of the first steps of human colonization on the plateau,” Dong says. “Those hunter-gathers might then expand to the inner plateau along the river valley.” The second study pushes back the dates of human settlement above 4,000 meters by 4,000 years. Qinghai Normal University archaeologist Guangliang Hou and some of his colleagues recently excavated an archaeological site dated to 11,500 years ago, which is in line with the second and more important wave of migration that Xu’s study suggests. Hou said at the geographical congress that the site, close to a main tributary of the Yellow River, is teeming with charcoal—a telltale sign of fire use by humans. “This may have helped the plateau dwellers to survive the harsh conditions at such high elevations nearing the end of the Younger Dryas,” he says. “It’s increasingly clear that there has been much earlier and much more persistent human occupation of the plateau than we previously thought,” Aldenderfer says. He stresses, however, that pieces are still missing from the puzzle: “More excavations are required to close those gaps.”
News Article | October 25, 2016
New computer analysis may have discovered traces of long-lost human cousins hiding within DNA from people in Melanesia, a region in the South Pacific encompassing Papua New Guinea and surrounding islands. Ryan Bohlender, Ph.D., a statistical geneticist at the University of Texas MD Anderson Cancer Center, said during the annual meeting of the American Society of Human Genetics on Oct. 20 that Melanesian people may carry genetic evidence of a previously unknown extinct third hominid species. According to Bohlender, the species is unlikely to be from the extinct Neanderthal or Denisovan species, but from a different, related species likely from a third branch of the hominid family tree. “We’re missing a population or we’re misunderstanding something about the relationships,” he said in a statement. While in the past many Neanderthal fossils have been found in Europe and Asia, information on the Denisovans is relatively unknown as only DNA from a finger bone and a few teeth found in a Siberian cave have been found. Bohlender and fellow researchers have calculated that Europeans and Chinese people carry about 2.8 percent of Neanderthal ancestry. It is also estimated that Europeans have no hint of Denisovan ancestry and Chinese people only have 0.1 percent. However, according to his calculations, 2.74 percent of the DNA in people in Papua New Guinea comes from Neanderthals and another 3to6 percent comes from Denisovans, which is significantly higher than in other groups of people. The significantly high percentage of extinct ancestry led Bohlender to believe a third group of hominids may have bred with the ancestors of Melanesians. “Human history is a lot more complicated than we thought it was,” Bohlender said. Bohlender isn’t the first to suggest that remnants of archaic human relatives may be preserved in human DNA after researchers in 2012 suggested that some people in Africa carry DNA heirlooms from an extinct hominid species. Another group of researchers, led by Eske Willerslev, an evolutionary geneticist at the Natural History Museum of Denmark in Copenhagen, recently came to a similar conclusion. In Willerslev’s research, Denisovan-like DNA was found from 83 aboriginal Australians and 25 people from native populations in Papua New Guinea highlands. However, the DNA is genetically distinct from Denisovans and may be from Homo erectus or the extinct hominids found in Indonesia known as Hobbits. However, there is another theory that researchers don’t know how genetically diverse Denisovans were. Mattias Jakobsson, an evolutionary geneticist at Uppsala University in Sweden, said a different branch of Denisovans may have been the group that mated with ancestors of Australians and Papuans. “Modern humans and archaic humans have met many times and had many children together,” he said.
News Article | November 4, 2016
Scientists at the Wayne State University School of Medicine's Center for Molecular Medicine and Genetics have shown for the first time the extent by which interactions between environmental exposures and genetic variation across individuals have a significant impact on human traits and diseases like diabetes, heart disease and obesity, strengthening the case for precision medicine initiatives. The discovery is particularly important when considering communities with different ancestries sharing the same risk environment -- the case for many urban communities, including Detroit, the researchers said. Generally, people may share the same genetic risk factors but their chances to develop a disease are increased by specific environmental exposures. Human environments are difficult to measure, especially when trying to study these complex interactions. For example, the researchers explained, it is hard to quantify the amount of stress in a person's life or the caffeine or vitamin content in their diets. "Both genes and environmental conditions are major influences on our health and who we are. For example, stress is a risk factor for cardiovascular disease; however, the actual risk to have a heart attack depends not only on the amount of stress in a person's life but also on the specific DNA sequences -- genetic variants -- that he or she inherited from their parents," said researcher Francesca Luca, Ph.D., who led the study with co-principal investigator Roger Pique-Regi, Ph.D. "The interplay between genetic variants and environments during human evolutionary history provided the driving force that shaped our genome. Today, genetic adaptations that helped us in the past to better store energy in fat, for example, can make us more likely to develop a disease like diabetes or obesity." Luca and Pique-Regi are assistant professors of molecular medicine and genetics, and of obstetrics and gynecology, and have spent three years working on the project with a dedicated team of collaborators that included several WSU students and postdoctoral fellows, including recent graduate Gregory Moyerbrailean, Ph.D.; graduate student Cynthia Kalita; postdoctoral fellow Allison Richards, Ph.D.; and third-year medical student Daniel Kurtz. Studying the interaction between genetic variants and environment is an incredibly complex problem to tackle at the organismal level. The WSU-based team explored, at the molecular level, gene expression changes across 250 different cellular environments, including caffeine, vitamins, metal ions, hormones, contaminants and common drugs. "Our cellular system simplifies the complexity of the environment, and allows us to develop robust statistical tests to identify 215 genes with an activity modulated by genetic variants that interact with our controlled environmental perturbations," Luca said. "Surprisingly, 50 percent of these interactions are in genes important for human traits and diseases. For example, one of these interactions in the GIPR gene suggests that caffeine intake in the presence of a genetic protective factor may decrease the risk to develop obesity. Similarly, low selenium intake, in the presence of a genetic risk factor in the LAMP3 gene, may further increase the risk for Parkinson's disease." This is the first time that large-scale genomic experiments have shown that an individual's personal environment and genetic makeup can directly affect and influence their health. The results of the project are presented in the open-access Genome Research article "High-throughput allele-specific expression across 250 environmental conditions," published last month. In addition to the Genome Research publication, the researchers presented two talks on their work at October's American Society of Human Genetics in Vancouver. The research team is now investigating the precise molecular mechanisms of the interactions, exploring additional environmental exposures -- including the human microbiome -- and performing similar studies in a large number of individuals of African American origin to explore a larger number of genetic variants.
News Article | November 2, 2016
VANCOUVER — Traces of long-lost human cousins may be hiding in modern people’s DNA, a new computer analysis suggests. People from Melanesia, a region in the South Pacific encompassing Papua New Guinea and surrounding islands, may carry genetic evidence of a previously unknown extinct hominid species, Ryan Bohlender reported October 20 at the annual meeting of the American Society of Human Genetics. That species is probably not Neandertal or Denisovan, but a different, related hominid group, said Bohlender, a statistical geneticist at the University of Texas MD Anderson Cancer Center in Houston. “We’re missing a population or we’re misunderstanding something about the relationships,” he said. This mysterious relative was probably from a third branch of the hominid family tree that produced Neandertals and Denisovans, an extinct distant cousin of Neandertals. While many Neandertal fossils have been found in Europe and Asia, Denisovans are known only from DNA from a finger bone and a couple of teeth found in a Siberian cave (SN: 12/12/15, p. 14). Bohlender isn’t the first to suggest that remnants of archaic human relatives may have been preserved in human DNA even though no fossil remains have been found. In 2012, another group of researchers suggested that some people in Africa carry DNA heirlooms from an extinct hominid species (SN: 9/8/12, p. 9). Less than a decade ago, scientists discovered that human ancestors mixed with Neandertals. People outside of Africa still carry a small amount of Neandertal DNA, some of which may cause health problems (SN: 3/5/16, p. 18). Bohlender and colleagues calculate that Europeans and Chinese people carry a similar amount of Neandertal ancestry: about 2.8 percent. Europeans have no hint of Denisovan ancestry, and people in China have a tiny amount — 0.1 percent, according to Bohlender’s calculations. But 2.74 percent of the DNA in people in Papua New Guinea comes from Neandertals. And Bohlender estimates the amount of Denisovan DNA in Melanesians is about 1.11 percent, not the 3 to 6 percent estimated by other researchers. While investigating the Denisovan discrepancy, Bohlender and colleagues came to the conclusion that a third group of hominids may have bred with the ancestors of Melanesians. “Human history is a lot more complicated than we thought it was,” Bohlender said. Another group of researchers, led by Eske Willerslev, an evolutionary geneticist at the Natural History Museum of Denmark in Copenhagen, recently came to a similar conclusion. Willerslev’s group examined DNA from 83 aboriginal Australians and 25 people from native populations in the Papua New Guinea highlands (SN: 10/15/16, p. 6). The researchers found Denisovan-like DNA in the study volunteers, the group reported October 13 in Nature. But the DNA is genetically distinct from Denisovans and may be from another extinct hominid. “Who this group is we don’t know,” Willerslev says. They could be Homo erectus or the extinct hominids found in Indonesia known as Hobbits (SN: 4/30/16, p. 7), he speculates. But researchers don’t know how genetically diverse Denisovans were, says Mattias Jakobsson, an evolutionary geneticist at Uppsala University in Sweden. A different branch of Denisovans could be the group that mated with ancestors of Australians and Papuans. Researchers know so little about the genetic makeup of extinct groups that it’s hard to say whether the extinct hominid DNA actually came from an undiscovered species, said statistical geneticist Elizabeth Blue of the University of Washington in Seattle. DNA has been examined from few Neandertal fossils, and Denisovan remains have been found only in that single cave in Siberia. Denisovans may have been widespread and genetically diverse. If that were the case, said Blue, the Papuan’s DNA could have come from a Denisovan population that had been separated from the Siberian Denisovans for long enough that they looked like distinct groups, much as Europeans and Asians today are genetically different from each other. But if Denisovans were not genetically diverse, the mysterious extinct ancestor could well be another species, she said. Jakobsson says he wouldn’t be surprised if there were other groups of extinct hominids that mingled with humans. “Modern humans and archaic humans have met many times and had many children together,” he said. Editor’s note: This story was updated October 24, 2016, to correct Ryan Bohlender’s estimate of the percentage of Denisovan DNA in people from Papua New Guinea.
News Article | February 28, 2017
MELVILLE, N.Y.--(BUSINESS WIRE)--Population Bio (PB) – a global leader in gene discovery announced, in support of World Rare Disease Day, its continued investment in its CNV Beacon® gene discovery platform which delivers new knowledge about rare diseases. The CNV Beacon® platform can discern subtypes of common diseases such as Parkinson’s and Alzheimer’s and show that they are actually an amalgam of rare diseases masquerading as one disease. Such newly defined genetic rare subtypes in common diseases may be informative to a rare disease when the causal genes are the same. As presented at the American Society of Human Genetics (ASHG) last October, “NUBPL Mutations Link Parkinson’s Disease and other Movement Disorders to Recessive Complex I Deficiency”, the research describes PB’s discovery that some Parkinson’s disease patients carry mutations in the NUBPL gene, which is known to cause an ultra-rare mitochondrial disorder in children called Complex I Deficiency (CID). "Our linking of NUBPL mutations in Parkinson’s Disease (PD) to CID in children is analogous to the connection found many years ago between Gaucher disease and Parkinson’s,” said Dr. Eli Hatchwell, Chief Scientific Officer, Population Bio. "The Gaucher/PD connection has resulted in an active area of pharmaceutical research and our hope is that the NUBPL/PD connection will follow a similar path and lead to a new class of therapeutics.” Population Bio’s patented approach to gene discovery in populations has also been adapted to find causative variants in individuals with developmental delay and intellectual disabilities. PB’s clinical studies in conjunction with a leading US genetics center have demonstrated that the CNV Beacon® technology is able to identify rare variants that are not detected using standard test methods such as chromosomal microarrays and exome sequencing. "With almost 5 percent of the world’s population – an estimated 350 million people – living with a rare condition, we understand the challenging diagnostic odyssey experienced by people with rare diseases," said Jim Chinitz, CEO Population Bio. “World Rare Disease Day raises awareness and solidarity, and our company is thrilled to be a year-round stakeholder by defining new rare diseases, improving diagnostics, generating new biological knowledge and inspiring novel targeted drug strategies.” Population Bio, Inc. (PB) is a privately held global gene discovery company leading the field of precision medicine. Built on extensive intellectual property, PB is empowering pharmaceutical companies to develop targeted therapies and companion diagnostics faster and more cost effectively. Addressing critical health concerns, PB’s patented technology is currently in clinical studies, collaborations and partnerships addressing complex neurological diseases, such as Autism, PML, Parkinson’s and Alzheimer’s, in addition to other common conditions having a genetic component such as endometriosis and peanut allergy. For more information go to: www.populationbio.com