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Title: Orion: Detecting regions of the human non-coding genome that are intolerant to variation using population genetics
Austin Authors: Gussow, Ayal B;Copeland, Brett R;Dhindsa, Ryan S;Wang, Quanli;Petrovski, Slavé;Majoros, William H;Allen, Andrew S;Goldstein, David B
Affiliation: Program in Computational Biology and Bioinformatics, Duke University, Durham, NC, United States of America
Institute for Genomic Medicine, Columbia University, New York, NY, United States of America
Department of Medicine, The University of Melbourne, Austin Health and Royal Melbourne Hospital, Melbourne, Victoria, Australia
Center for Genomic and Computational Biology, Duke University, Durham, NC, United States of America
Department of Biostatistics and Bioinformatics, Duke University, Durham NC, United States of America. Abstract
Issue Date: 10-Aug-2017
Date: 2017-08-10
Publication information: PLoS One 2017; 12(8): e0181604
Abstract: There is broad agreement that genetic mutations occurring outside of the protein-coding regions play a key role in human disease. Despite this consensus, we are not yet capable of discerning which portions of non-coding sequence are important in the context of human disease. Here, we present Orion, an approach that detects regions of the non-coding genome that are depleted of variation, suggesting that the regions are intolerant of mutations and subject to purifying selection in the human lineage. We show that Orion is highly correlated with known intolerant regions as well as regions that harbor putatively pathogenic variation. This approach provides a mechanism to identify pathogenic variation in the human non-coding genome and will have immediate utility in the diagnostic interpretation of patient genomes and in large case control studies using whole-genome sequences.
DOI: 10.1371/journal.pone.0181604
Journal: PLoS One
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

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