An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people.

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State: Public
Version: Final published version
Serval ID
serval:BIB_1BDEA25840E5
Type
Article: article from journal or magazin.
Collection
Publications
Title
An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people.
Journal
Science
Author(s)
Nelson M.R., Wegmann D., Ehm M.G., Kessner D., St Jean P., Verzilli C., Shen J., Tang Z., Bacanu S.A., Fraser D., Warren L., Aponte J., Zawistowski M., Liu X., Zhang H., Zhang Y., Li J., Li Y., Li L., Woollard P., Topp S., Hall M.D., Nangle K., Wang J., Abecasis G., Cardon L.R., Zöllner S., Whittaker J.C., Chissoe S.L., Novembre J., Mooser V.
ISSN
1095-9203 (Electronic)
ISSN-L
0036-8075
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
337
Number
6090
Pages
100-104
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish. pdf-type:report
Abstract
Rare genetic variants contribute to complex disease risk; however, the abundance of rare variants in human populations remains unknown. We explored this spectrum of variation by sequencing 202 genes encoding drug targets in 14,002 individuals. We find rare variants are abundant (1 every 17 bases) and geographically localized, so that even with large sample sizes, rare variant catalogs will be largely incomplete. We used the observed patterns of variation to estimate population growth parameters, the proportion of variants in a given frequency class that are putatively deleterious, and mutation rates for each gene. We conclude that because of rapid population growth and weak purifying selection, human populations harbor an abundance of rare variants, many of which are deleterious and have relevance to understanding disease risk.
Keywords
African Americans/genetics, Asian Continental Ancestry Group, Disease/genetics, European Continental Ancestry Group/genetics, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Geography, High-Throughput Nucleotide Sequencing, Humans, Molecular Targeted Therapy, Multifactorial Inheritance, Mutation Rate, Pharmacogenetics, Phenotype, Polymorphism, Single Nucleotide, Population Growth, Sample Size, Selection, Genetic
Pubmed
Web of science
Create date
10/01/2013 11:23
Last modification date
20/08/2019 12:52
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