| Literature DB >> 27065010 |
Rong Chen1,2, Lisong Shi1,2, Jörg Hakenberg1,2, Brian Naughton3, Pamela Sklar1,2,4, Jianguo Zhang5, Hanlin Zhou5, Lifeng Tian6, Om Prakash7, Mathieu Lemire8, Patrick Sleiman6, Wei-Yi Cheng1,2, Wanting Chen5, Hardik Shah1,2, Yulan Shen5, Menachem Fromer1,2,4, Larsson Omberg9, Matthew A Deardorff6, Elaine Zackai6, Jason R Bobe1,2, Elissa Levin1,2, Thomas J Hudson8, Leif Groop7, Jun Wang10, Hakon Hakonarson6, Anne Wojcicki3, George A Diaz1,2, Lisa Edelmann1,2, Eric E Schadt1,2, Stephen H Friend1,2,9.
Abstract
Genetic studies of human disease have traditionally focused on the detection of disease-causing mutations in afflicted individuals. Here we describe a complementary approach that seeks to identify healthy individuals resilient to highly penetrant forms of genetic childhood disorders. A comprehensive screen of 874 genes in 589,306 genomes led to the identification of 13 adults harboring mutations for 8 severe Mendelian conditions, with no reported clinical manifestation of the indicated disease. Our findings demonstrate the promise of broadening genetic studies to systematically search for well individuals who are buffering the effects of rare, highly penetrant, deleterious mutations. They also indicate that incomplete penetrance for Mendelian diseases is likely more common than previously believed. The identification of resilient individuals may provide a first step toward uncovering protective genetic variants that could help elucidate the mechanisms of Mendelian diseases and new therapeutic strategies.Entities:
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Year: 2016 PMID： 27065010 DOI： 10.1038/nbt.3514
Source DB: PubMed Journal: Nat Biotechnol ISSN： 1087-0156 Impact factor: 54.908