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Archive - Oct 18, 2018

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Environmental Associations with Genes May Yield Opportunities for Precision Medicine; Findings Reported at ASHG 2018 Annual Meeting

A new approach to genetic analysis finds associations between environmental factors and pharmacogenes – genes associated with a person’s response to drugs – sparking ideas for new research at the interface of population genetics and medicine. Findings were presented Thursday, October 18, at the American Society of Human Genetics (ASHG) 2018 Annual Meeting in San Diego, California (October 16-20). “Humans have developed and used pharmaceutical drugs for a few centuries, but their genes have been functioning on their own and interacting with other environmental factors for long before that,” explained presenting author Chris Gignoux (photo), PhD, of the University of Colorado Anschutz Medical Campus. Like changes in the physical environment, drugs affect the micro- environment within the body, which alters the way its cells and genes function. This suggests that genes with pharmacogenomic relevance may also be useful in studying broader correlations between genetics and environment. To explore a variety of environmental factors, Dr. Gignoux collaborated with Elena Sorokin, PhD, of Stanford University, who created a geocoded resource of over 20 climate, geographic, and ecological variables, using data from NASA, the World Wildlife Fund, and other sources. With collaborators from across the United States, they examined samples from the Population Architecture using Genomics and Epidemiology (PAGE) Study, a large initiative to highlight the utility of studying clinically and epidemiologically relevant variation in 51,698 individuals from 99 global populations. In a new type of analysis they termed an Enviro-WAS (environment-wide association study), the researchers examined 19,690 pharmacogenomically-relevant variants to identify associations between genotypes and the 20 environmental variables.

Docs May Be Overly Conservative in Use of New Drug Combinations for Cancer, UCSD Speaker Suggests; Over 4 Million Three-Drug Combinations of Existing Drugs Possible, Too Many for Clinical Trials; Biomarker Use to Target Treatment Is Recommended

(BY MICHAEL A. GOLDMAN, PhD, Professor, Former Chairman of Biology, San Francisco State University). Speaking at this week's 2018 annual meeting of the American Society for Human Genetics (ASHG) in San Diego (October 16-20), Razelle Kurzrock (photo),MD, Director of the UC San Diego (UCSD) Center for Personalized Cancer Therapy, told a very large audience that oncologists have been conservative about using new drug combination therapies. Yet, with nearly 300 drugs on the market, there are more than 4 million 3-drug combinations, far too many to test in controlled trials. She uses a patient-centric, rather than a drug-centric, treatment plan, employing a consistent strategy, but with different drugs or, when appropriate, immunotherapy. Addressing more than 600 scientists and clinicians in a two-day symposium sponsored by the Pharmacogenomics Research Network (PGRN), Dr. Kurzrock said cancers are like malignant snowflakes, each different and magnificently complex. Profiling more than 12,000 tumors using genomic markers, her group uses biomarkers to target treatment in a "tissue-agnostic" manner. For example, PIK3CA mutations are found in 10% of patients with advanced cancers, and can be seen in a subset of most cancer types. Elevated HER2 expression occurs across a wide variety of tumors, and the same HER2 antagonists seem to work. Dr. Kurzrock calls her approach PREDICT (Profile-Related Evidence Determining Individual Cancer Therapy), which reflects a family of master protocols at UCSD. These protocols for trial combinations of drugs have limited exclusion criteria; almost every patient in need is eligible. Dr. Kurzrock stressed the need for genomics education for medical professionals, which she finds to be inadequate today. "In five years," she says, "it will be routine practice to do these [genomic] tests."

EXOSOME NEWS: Fat Cells & Extracellular Vesicles (EVs) They Release May Hold Solutions for Diabetes; “Findings Represent a New Way of Thinking for Researchers Who Study Diabetes, Obesity, and Metabolism”

Researchers have long known that cells in the human body communicate with one another. Now a team of scientists at the University of Texas (UT) Southwestern Medical Center is hacking into this communication network to learn how fat cells talk with other cells and tissues in the body. Dr. Philipp Scherer, a metabolism expert and Director of the Touchstone Center for Diabetes Research at UT Southwestern, is excited about the new findings because they will allow researchers to test new ideas and re-examine old ones. The study, published online on October 4, 2018 in Cell, shows that fat cells communicate with endothelial cells of the blood vessels that course through fat tissue, and potentially with other organs, by secreted packages of information (extracellular vesicles or EVs, often called exosomes). This communication between cells was demonstrated in a number of new mouse models that researchers created. The title of the new article is “An Endothelial-to-Adipocyte Extracellular Vesicle Axis Governed by Metabolic State.” These findings represent a new way of thinking for researchers who study diabetes, obesity, and metabolism. They open an entirely new door to our understanding of how tissues communicate,” said Dr. Clair Crewe, a postdoctoral researcher in the Touchstone Diabetes Center and first author of the study. “Once we understand the communication process, we can potentially shape it to either enhance or reduce the signaling effect.” The study identified a type of vesicle, a membrane-enclosed sphere, released by fat and other cells. Dr. Scherer compares them to the chocolate surrounding a bonbon. The “filling” includes lipids, signaling molecules, and proteins. The timing of their release is regulated by cycles of fasting and feeding. These vesicles travel throughout the body.

Ancient Andean Genomes Show Distinct Adaptations to Farming and Altitude; Findings Presented at ASHG 2018 Annual Meeting

Ancient populations in the Andes mountains of Peru adapted to their high-altitude environment and the introduction of agriculture in ways distinct from other global populations that faced similar circumstances, according to findings presented on October 17 at the American Society of Human Genetics (ASHG) 2018 Annual Meeting in San Diego, California (October 16-20). The ASHG has reported a record attendance of 8,500 at this year’s meeting. John Lindo, PhD, JD, Assistant Professor of Anthropology at Emory University, and a group of international collaborators headed by Anna Di Rienzo, PhD, at the University of Chicago and Mark Aldenderfer, PhD, at the University of California, Merced, set out to use newly available samples of 7,000-year-old DNA from seven whole genomes to study how ancient people in the Andes adapted to their environment. The scientists compared these genomes with 64 modern-day genomes from both highland Andean populations and lowland populations in Chile, in order to identify the genetic adaptations that took place before the arrival of Europeans in the 1500’s. “Contact with Europeans had a devastating impact on South American populations, such as the introduction of disease, war, and social disruption,” explained Dr. Lindo. “By focusing on the period before that, we were able to distinguish environmental adaptations from adaptations that stemmed from historical events.” The scientists found that Andean populations’ genomes adapted to the introduction of agriculture and resulting increase in starch consumption differently from other populations. For example, the genomes of European farming populations show an increased number of copies of the gene coding for amylase, an enzyme in saliva that helps break down starch.