title: A composite of multiple signals distinguishes causal variants in regions of positive selection.
abstract: The human genome contains hundreds of regions whose patterns of genetic variation indicate recent positive natural selection, yet for most the underlying gene and the advantageous mutation remain unknown. We developed a method, composite of multiple signals (CMS), that combines tests for multiple signals of selection and increases resolution by up to 100-fold. By applying CMS to candidate regions from the International Haplotype Map, we localized population-specific selective signals to 55 kilobases (median), identifying known and novel causal variants. CMS can not just identify individual loci but implicates precise variants selected by evolution.
authors.affiliation: Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. shari.grossman@post.harvard.edu
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Grossman
authors.forename: Ilya
authors.initials: I
authors.lastname: Shlyakhter
authors.forename: Ilya
authors.initials: I
authors.lastname: Shylakhter
authors.forename: Elinor K
authors.initials: EK
authors.lastname: Karlsson
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Byrne
authors.forename: Shannon
authors.initials: S
authors.lastname: Morales
authors.forename: Gabriel
authors.initials: G
authors.lastname: Frieden
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hostetter
authors.forename: Elaine
authors.initials: E
authors.lastname: Angelino
authors.forename: Manuel
authors.initials: M
authors.lastname: Garber
authors.forename: Or
authors.initials: O
authors.lastname: Zuk
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Schaffner
authors.forename: Pardis C
authors.initials: PC
authors.lastname: Sabeti
mesh_terms: D019295:Computational Biology / Q000379:methods; D021901:DNA, Intergenic / Q000235:genetics; D019143:Evolution, Molecular; D056426:Genetic Loci; D014644:Genetic Variation; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D011110:Polymorphism, Genetic; D044382:Population Groups / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012641:Selection, Genetic; D012984:Software
chemical_list: D021901:DNA, Intergenic