Journal article
The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity
Slave Petrovski, Ayal B Gussow, Quanli Wang, Matt Halvorsen, Yujun Han, William H Weir, Andrew S Allen, David B Goldstein
PLOS GENETICS | PUBLIC LIBRARY SCIENCE | Published : 2015
Abstract
Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory mutations are notoriously difficult to recognize. Most fundamentally, we are not yet adept at recognizing the sequence stretches in the human genome that are most important in regulating the expression of genes. For this reason, it is difficult to apply to the regulatory regions the same kinds of analytical paradigms that are being successfully applied to identify mutations among protein-coding regions that influence risk. To determine whether dosage sensitive genes have distinct patterns among their noncoding sequence, we present two primary approaches that focus ..
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Grants
Awarded by NIH NINDS Epi4K Sequencing, Bioinformatics and Biostatistics Core grant
Awarded by National Institute Of Neurological Disorders and Stroke of National Institutes of Health
Awarded by Bryan ADRC
Awarded by SAIC-Frederick, Inc.
Awarded by Henry M. Jackson Foundation
Awarded by NIMH
Awarded by NINDS
Awarded by Center for HIV/AIDS Vaccine Immunology ("CHAVI") from National Institute of Allergy and Infectious Diseases, National Institutes of Health
Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
Awarded by NATIONAL INSTITUTE OF MENTAL HEALTH
Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Awarded by NATIONAL INSTITUTE ON AGING
Funding Acknowledgements
This work was supported in part by Biogen Idec MA and the NIH NINDS Epi4K Sequencing, Bioinformatics and Biostatistics Core grant number U01NS077303. SP is a National Health and Medical Research Council of Australia (NHMRC) (CJ Martin) Early Career Fellow (1035130). ABG is supported by the National Institute Of Neurological Disorders and Stroke of the National Institutes of Health under Award Number F31NS092362. The collection of control samples was funded in part by Bryan ADRC NIA P30 AG028377, an award from SAIC-Frederick, Inc. (M11-074), an award from the Henry M. Jackson Foundation (W81XWH-07-2-0067), NIMH awards RC2MH089915 and K01MH098126, NINDS awards 1RC2NS070342-01 and RC2NS070344, and the Center for HIV/AIDS Vaccine Immunology ("CHAVI") under a grant from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (U01AIO67854). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.