This message contains search results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM). Do not reply directly to this message
Sent on: Tue May 22 12:27:53 2012
1 selected item: 22604722

PubMed Results

Item 1 of 1    (Display the citation in PubMed)

1.	Science. 2012 May 17. [Epub ahead of print] An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People. Nelson MR, Wegmann D, Ehm MG, Kessner D, St Jean P, Verzilli C, Shen J, Tang Z, Bacanu SA, 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 MD, Nangle K, Wang J, Abecasis G, Cardon LR, Zöllner S, Whittaker JC, Chissoe SL, Novembre J, Mooser V. Source Quantitative Sciences, GlaxoSmithKline, RTP, NC, USA; Upper Merion, PA, USA; and Stevenage, UK. 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 (one every 17 bases) and geographically localized, such 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. Overall, we conclude that, due to 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.
	PMID: 22604722 [PubMed - as supplied by publisher]