title: Identifying recent adaptations in large-scale genomic data.
abstract: 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:
authors: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. grossman@broadinstitute.org
authors: Sharon R
authors: SR
authors: Grossman
authors: Kristian G
authors: KG
authors: Andersen
authors: Ilya
authors: I
authors: Shlyakhter
authors: Shervin
authors: S
authors: Tabrizi
authors: Sarah
authors: S
authors: Winnicki
authors: Angela
authors: A
authors: Yen
authors: Daniel J
authors: DJ
authors: Park
authors: Dustin
authors: D
authors: Griesemer
authors: Elinor K
authors: EK
authors: Karlsson
authors: Sunny H
authors: SH
authors: Wong
authors: Moran
authors: M
authors: Cabili
authors: Richard A
authors: RA
authors: Adegbola
authors: Rameshwar N K
authors: RN
authors: Bamezai
authors: Adrian V S
authors: AV
authors: Hill
authors: Fredrik O
authors: FO
authors: Vannberg
authors: John L
authors: JL
authors: Rinn
authors: Eric S
authors: ES
authors: Lander
authors: Stephen F
authors: SF
authors: Schaffner
authors: Pardis C
authors: PC
authors: Sabeti
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism; D005408:Flagellin / Q000378:metabolism; D005821:Genetic Techniques; D015894:Genome, Human; D055106:Genome-Wide Association Study; D060148:HapMap Project; D006801:Humans; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D040641:Quantitative Trait Loci; D050436:Regulatory Elements, Transcriptional; D015398:Signal Transduction; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin