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Cell DOI:10.1016/j.cell.2013.01.035

Identifying recent adaptations in large-scale genomic data.

Publication TypeJournal Article
Year of Publication2013
AuthorsGrossman, SR, Andersen, KG, Shlyakhter, I, Tabrizi, S, Winnicki, S, Yen, A, Park, DJ, Griesemer, D, Karlsson, EK, Wong, SH, Cabili, M, Adegbola, RA, Bamezai, RNK, Hill, AVS, Vannberg, FO, Rinn, JL, Lander, ES, Schaffner, SF, Sabeti, PC
Corporate Authors1000 Genomes Project
Date Published2013 Feb 14
KeywordsAnimals, Bacteria, Flagellin, Genetic Techniques, Genome, Human, Genome-Wide Association Study, HapMap Project, Humans, Mutation, NF-kappa B, Quantitative Trait Loci, Regulatory Elements, Transcriptional, Signal Transduction, Toll-Like Receptor 5

Although several hundred regions of the human genome harbor signals of positive natural selection, few of the relevant adaptive traits and variants have been elucidated. Using full-genome sequence variation from the 1000 Genomes (1000G) Project and the composite of multiple signals (CMS) test, we investigated 412 candidate signals and leveraged functional annotation, protein structure modeling, epigenetics, and association studies to identify and extensively annotate candidate causal variants. The resulting catalog provides a tractable list for experimental follow-up; it includes 35 high-scoring nonsynonymous variants, 59 variants associated with expression levels of a nearby coding gene or lincRNA, and numerous variants associated with susceptibility to infectious disease and other phenotypes. We experimentally characterized one candidate nonsynonymous variant in Toll-like receptor 5 (TLR5) and show that it leads to altered NF-κB signaling in response to bacterial flagellin. PAPERFLICK:


Alternate JournalCell
PubMed ID23415221
PubMed Central IDPMC3674781
Grant ListAI2009061 / AI / NIAID NIH HHS / United States
1DP2OD006514-01 / OD / NIH HHS / United States
/ / Medical Research Council / United Kingdom
T32 HG002295 / HG / NHGRI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
090532 / / Wellcome Trust / United Kingdom
T32GM007753 / GM / NIGMS NIH HHS / United States
DP2 OD006514 / OD / NIH HHS / United States
/ / Wellcome Trust / United Kingdom