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Patterns of genic intolerance of rare copy number variation in 59,898 human exomes.

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Title: Patterns of genic intolerance of rare copy number variation in 59,898 human exomes.
Authors: Ruderfer, DM
Hamamsy, T
Lek, M
Karczewski, KJ
Kavanagh, D
Samocha, KE
Exome Aggregation Consortium
Daly, MJ
MacArthur, DG
Fromer, M
Purcell, SM
Item Type: Journal Article
Abstract: Copy number variation (CNV) affecting protein-coding genes contributes substantially to human diversity and disease. Here we characterized the rates and properties of rare genic CNVs (<0.5% frequency) in exome sequencing data from nearly 60,000 individuals in the Exome Aggregation Consortium (ExAC) database. On average, individuals possessed 0.81 deleted and 1.75 duplicated genes, and most (70%) carried at least one rare genic CNV. For every gene, we empirically estimated an index of relative intolerance to CNVs that demonstrated moderate correlation with measures of genic constraint based on single-nucleotide variation (SNV) and was independently correlated with measures of evolutionary conservation. For individuals with schizophrenia, genes affected by CNVs were more intolerant than in controls. The ExAC CNV data constitute a critical component of an integrated database spanning the spectrum of human genetic variation, aiding in the interpretation of personal genomes as well as population-based disease studies. These data are freely available for download and visualization online.
Issue Date: 17-Aug-2016
Date of Acceptance: 12-Jul-2016
URI: http://hdl.handle.net/10044/1/49964
DOI: https://dx.doi.org/10.1038/ng.3638
ISSN: 1061-4036
Publisher: Nature Publishing Group
Start Page: 1107
End Page: 1111
Journal / Book Title: Nature Genetics
Volume: 48
Issue: 10
Copyright Statement: © 2016 Nature America, Inc. All rights reserved.
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
HUMAN GENOME
STRUCTURAL VARIATION
HUMAN-DISEASE
SCHIZOPHRENIA
IDENTIFICATION
VARIANTS
SEQUENCE
BURDEN
MAP
Adult
Child
DNA Copy Number Variations
Databases, Genetic
Exome
Female
Gene Frequency
Genetic Predisposition to Disease
Genome, Human
Humans
Male
Polymorphism, Single Nucleotide
Schizophrenia
Exome Aggregation Consortium
11 Medical And Health Sciences
06 Biological Sciences
Developmental Biology
Publication Status: Published
Conference Place: United States
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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