Journal article
Orion: Detecting regions of the human noncoding genome that are intolerant to variation using population genetics
AB Gussow, BR Copeland, RS Dhindsa, Q Wang, S Petrovski, WH Majoros, AS Allen, DB Goldstein
Plos One | PUBLIC LIBRARY SCIENCE | Published : 2017
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 varia..
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Awarded by National Institute of General Medical Sciences
Funding Acknowledgements
This work was supported by the National Institute of Mental Health of the National Institutes of Health under Award Number 1U01 MH105670 and by the National Human Genome Research Institute of the National Institutes of Health under the Centers for Common Disease Genomics Award Number 1UM1HG00901. ABG was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number F31NS092362. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The collection of samples and data was funded in part by: Biogen, Inc.; Bryan ADRC NIA P30AG028377; B57 SAIC-Fredrick Inc M11074; National Institute of Neurological Disorders and Stroke (RC2NS070344; U01NS077303; U01NS053998); National Institute of Mental Health (RC2MH089915, K01MH098126, R01MH097971); National Human Genome Research Institute (U01HG007672); Center for HIV/AIDS Vaccine Immunology (CHAVI) (U19-AI067854); National Institute of Allergy and Infectious Diseases Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (UM1-AI100645); Bill and Melinda Gates Foundation; the Ellison Medical Foundation New Scholar award AG-NS-0441-08; and the Murdock Study Community Registry and Biorepository.