title: Searching for signals of evolutionary selection in 168 genes related to immune function.
abstract: Pathogens have played a substantial role in human evolution, with past infections shaping genetic variation at loci influencing immune function. We selected 168 genes known to be involved in the immune response, genotyped common single nucleotide polymorphisms across each gene in three population samples (CEPH Europeans from Utah, Han Chinese from Guangxi, and Yoruba Nigerians from Southwest Nigeria) and searched for evidence of selection based on four tests for non-neutral evolution: minor allele frequency (MAF), derived allele frequency (DAF), Fst versus heterozygosity and extended haplotype homozygosity (EHH). Six of the 168 genes show some evidence for non-neutral evolution in this initial screen, with two showing similar signals in independent data from the International HapMap Project. These analyses identify two loci involved in immune function that are candidates for having been subject to evolutionary selection, and highlight a number of analytical challenges in searching for selection in genome-wide polymorphism data.
authors.affiliation: Novartis Institutes for Biomedical Research, 250 Mass Ave, Cambridge, MA 02139, USA. Emily.walsh@novartis.com
authors.forename: Emily C
authors.initials: EC
authors.lastname: Walsh
authors.forename: Pardis
authors.initials: P
authors.lastname: Sabeti
authors.forename: Holli B
authors.initials: HB
authors.lastname: Hutcheson
authors.forename: Ben
authors.initials: B
authors.lastname: Fry
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Schaffner
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.forename: Patrick
authors.initials: P
authors.lastname: Varilly
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Palma
authors.forename: Jessica
authors.initials: J
authors.lastname: Roy
authors.forename: Richard
authors.initials: R
authors.lastname: Cooper
authors.forename: Cheryl
authors.initials: C
authors.lastname: Winkler
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.forename: Guy
authors.initials: G
authors.lastname: de The
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Brien
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
mesh_terms: D000465:Algorithms; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D016000:Cluster Analysis; D019143:Evolution, Molecular; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D012984:Software; D044465:White People / Q000235:genetics