A composite of multiple signals distinguishes causal variants in regions of positive selection.
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.
Grossman
Sharon R
SR
Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. shari.grossman@post.harvard.edu
Shlyakhter
Ilya
I
Shylakhter
Ilya
I
Karlsson
Elinor K
EK
Byrne
Elizabeth H
EH
Morales
Shannon
S
Frieden
Gabriel
G
Hostetter
Elizabeth
E
Angelino
Elaine
E
Garber
Manuel
M
Zuk
Or
O
Lander
Eric S
ES
Schaffner
Stephen F
SF
Sabeti
Pardis C
PC
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
D021901:DNA, Intergenic