Publication Date:
2012-05-19
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319976/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319976/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nelson, Matthew R -- Wegmann, Daniel -- Ehm, Margaret G -- Kessner, Darren -- St Jean, Pamela -- Verzilli, Claudio -- Shen, Judong -- Tang, Zhengzheng -- Bacanu, Silviu-Alin -- Fraser, Dana -- Warren, Liling -- Aponte, Jennifer -- Zawistowski, Matthew -- Liu, Xiao -- Zhang, Hao -- Zhang, Yong -- Li, Jun -- Li, Yun -- Li, Li -- Woollard, Peter -- Topp, Simon -- Hall, Matthew D -- Nangle, Keith -- Wang, Jun -- Abecasis, Goncalo -- Cardon, Lon R -- Zollner, Sebastian -- Whittaker, John C -- Chissoe, Stephanie L -- Novembre, John -- Mooser, Vincent -- T32 HG002536/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2012 Jul 6;337(6090):100-4. doi: 10.1126/science.1217876. Epub 2012 May 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Quantitative Sciences, GlaxoSmithKline (GSK), Research Triangle Park, NC 27709, USA. matthew.r.nelson@gsk.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22604722" target="_blank"〉PubMed〈/a〉
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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