Human Genetics

, Volume 119, Issue 1, pp 92–102

Searching for signals of evolutionary selection in 168 genes related to immune function

Authors

    • Novartis Institutes for Biomedical Research
    • Broad Institute of MIT and Harvard
  • Pardis Sabeti
    • Broad Institute of MIT and Harvard
  • Holli B. Hutcheson
    • Laboratory of Genomic DiversityNational Cancer Institute
  • Ben Fry
    • Broad Institute of MIT and Harvard
  • Stephen F. Schaffner
    • Broad Institute of MIT and Harvard
  • Paul I. W. de Bakker
    • Broad Institute of MIT and Harvard
    • Massachusetts General Hospital
  • Patrick Varilly
    • Broad Institute of MIT and Harvard
  • Alejandro A. Palma
    • Broad Institute of MIT and Harvard
  • Jessica Roy
    • Broad Institute of MIT and Harvard
  • Richard Cooper
    • Department of Preventive Medicine and EpidemiologyLoyola University Medical School
  • Cheryl Winkler
    • Laboratory of Genomic DiversityNational Cancer Institute
  • Yi Zeng
    • Institute for Viral Disease Control and Prevention
  • Guy de The
    • The Institute Pasteur
  • Eric S. Lander
    • Broad Institute of MIT and Harvard
  • Stephen O’Brien
    • Laboratory of Genomic DiversityNational Cancer Institute
  • David Altshuler
    • Broad Institute of MIT and Harvard
    • Massachusetts General Hospital
    • Harvard Medical School
Original Investigation

DOI: 10.1007/s00439-005-0090-0

Cite this article as:
Walsh, E.C., Sabeti, P., Hutcheson, H.B. et al. Hum Genet (2006) 119: 92. doi:10.1007/s00439-005-0090-0

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.

Supplementary material

439_2005_90_MOESM1_ESM.pdf (766 kb)
Supplementary material

Copyright information

© Springer-Verlag 2005