Clinical OMICs - Issue 3 - (Page 12)

Bringing Informed Interpretation to Vexing Variants Alex Philippidis W hile the first traffic light flashed 18 years before the first car was built, the rules of the road have long lagged behind technology where genetic testing is concerned, especially in distinguishing functional gene variants from those that cause disease. That is starting to change as groups of researchers and clinicians hammer out guidelines for statistically rigorous and evidence-based clinical interpretation of variants found through next-generation sequencing. On April 23, a working group of 27 experts in genomic research, analysis, and clinical diagnostic sequencing convened in a 2012 workshop by the NIH's National Human Genome Research Institute (NHGRI) published an open-access paper in Nature presenting its proposed guidelines for evaluating evidence supporting variant causality. Daniel MacArthur, Ph.D., of Massachusetts General Hospital and Chris Gunter, Ph.D., of Marcus Autism Center and Emory University, led the working group in drawing up guidelines that cover evidence assessment for candidate disease genes and candidate pathogenic variants, as well as standards for reporting, publishing, and even sharing data. The group listed priorities for research and infrastrucALEX PHILIPPIDIS ture development: Developing standardized, quantitaspecializes in biopharma business news tive statistical approaches for assigning probability of and industry issues. Alex joined GEN in causation; large-scale genotyping of reported disease2011 after four years at GenomeWeb, where he covered research institutes and causing variants; building public databases of those biotech economic development topics. variants, with up-to-date supporting evidence, plus Previously, Alex worked more than 20 years variant and allele frequency data from large, diverse for various newspapers covering business, science, and population samples; and greater sharing of data by general news topics. He has been interviewed and quoted research and clinical labs. by news outlets that include The New York Times and the "We have seen so many more large cohorts and huge BBC. ( amounts of sequence generated, and we have seen things go wrong as well as right over time," Dr. Gunter told GEN. "Much more is needed on both the research and infrastructure fronts to stringently assign causality to sequence variants." 12 Clinical OMICs May 15, 2014

Table of Contents for the Digital Edition of Clinical OMICs - Issue 3


Clinical OMICs - Issue 3