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Archive - Nov 18, 2012

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Stanford/Yale Study Gives Insight into Subtle Genomic Differences Among Our Own Cells

Stanford University School of Medicine scientists have demonstrated, in a study conducted jointly with researchers at Yale University, that induced-pluripotent stem cells (iPS cells) — the embryonic-stem-cell lookalikes whose discovery a few years ago won this year's Nobel Prize in medicine — are not as genetically unstable as was thought. The new study, which was published online on Novenber 18, 2012 in Nature, showed that what seemed to be changes in iPS cells' genetic makeup — presumed to be inflicted either in the course of their generation from adult cells or during their propagation and maintenance in laboratory culture dishes — instead are often accurate reflections of existing but previously undetected genetic variations among the cells comprising our bodies. That's good news for researchers hoping to use the cells to study disease or, someday, for regenerative medicine. But it raises the question of whether and to what extent we humans are really walking mosaics whose constituent cells differ genetically from one to the next in possibly significant respects, said Alexander Urban, Ph.D., assistant professor of psychiatry and behavioral sciences at Stanford. Dr. Urban shared senior authorship of the study with bioinformatics professor Mark Gerstein, Ph.D., and neurobiology professor Flora Vaccarino, M.D., both of Yale. It's only a few years ago that human iPS cells started becoming available to researchers. These cells hold great promise because they act almost exactly like embryonic stem cells, which can be nudged to differentiate into virtually any of the body's roughly 200 different cell types. But iPS cells can be derived easily from a person's skin, alleviating numerous ethical concerns arising from the necessity of obtaining embryonic stem cells from fertilized eggs.

Variants of TREM2 Gene Nearly Triple Risk of Alzheimer's

A gene so powerful it nearly triples the risk of Alzheimer's disease has been discovered by an international team including researchers from the Mayo Clinic. It is the most potent genetic risk factor for Alzheimer's identified in the past 20 years. The findings were reported November 14, 2012 in the online edition of the New England Journal of Medicine. The team included researchers from 44 institutions around the world, including 10 from the Mayo Clinic's campuses in Florida and Minnesota. The study was led by John Hardy, Ph.D., a researcher at the Institute of Neurology at University College London and a former professor at Mayo Clinic in Florida. The researchers used new sequencing techniques to home in on the TREM2 gene. Additional TREM2 sequencing was then performed, in part, by scientist Dr. Aleksandra Wojtas in the Mayo Clinic in Florida laboratory of Rosa Rademaker, Ph.D. These studies led to identification of a set of rare variants in TREM2 that occurred more often in 1,092 Alzheimer's disease patients than in a control group of 1,107 healthy people. The most common variant, R47H, was then evaluated in follow-up studies of a large number of Alzheimer's disease patients and controls. Minerva Carrasquillo, Ph.D., a scientist in the Mayo Clinic in Florida laboratory of Steven Younkin, M.D., Ph.D., spearheaded the direct genotyping and analysis of R47H in DNA samples from 1,994 Alzheimer's disease patients and 4,062 "control" participants — individuals verified not to have Alzheimer's. The patients and control participants were evaluated by Mayo Clinic physicians, led by co-authorsDennis Dickson, M.D., Neill Graff-Radford, M.D., and Ronald Petersen, M.D., Ph.D.