title: Screening for recently selected alleles by analysis of human haplotype similarity.
abstract: There is growing interest in the use of haplotype-based methods for detecting recent selection. Here, we describe a method that uses a sliding window to estimate similarity among the haplotypes associated with any given single-nucleotide polymorphism (SNP) allele. We used simulations of natural selection to provide estimates of the empirical power of the method to detect recently selected alleles and found it to be comparable in power to the popular long-range haplotype test and more powerful than methods based on nucleotide diversity. We then applied the method to a recently selected allele--the sickle mutation at the HBB locus--and found it to have a signal of selection that was significantly stronger than that of simulated models both with and without strong selection. Using this method, we also evaluated >4,000 SNPs on chromosome 20, indicating the applicability of the method to regional data sets.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom. neil.hanchard@green-oxford.com
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hanchard
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Rockett
authors.forename: Chris
authors.initials: C
authors.lastname: Spencer
authors.forename: Graham
authors.initials: G
authors.lastname: Coop
authors.forename: Margaret
authors.initials: M
authors.lastname: Pinder
authors.forename: Muminatou
authors.initials: M
authors.lastname: Jallow
authors.forename: Martin
authors.initials: M
authors.lastname: Kimber
authors.forename: Gil
authors.initials: G
authors.lastname: McVean
authors.forename: Richard
authors.initials: R
authors.lastname: Mott
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Kwiatkowski
mesh_terms: D000483:Alleles; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D003198:Computer Simulation; D014644:Genetic Variation; D005828:Genetics, Population / Q000379:methods*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic