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

Springer Science and Business Media LLC - Tập 119 - Trang 92-102 - 2005
Emily C. Walsh1,2, Pardis Sabeti2, Holli B. Hutcheson3, Ben Fry2, Stephen F. Schaffner2, Paul I. W. de Bakker2,4, Patrick Varilly2, Alejandro A. Palma2, Jessica Roy2, Richard Cooper5, Cheryl Winkler3, Yi Zeng6, Guy de The7, Eric S. Lander2, Stephen O’Brien3, David Altshuler2,4,8
1Novartis Institutes for BioMedical Research, Cambridge, USA
2Broad Institute of MIT and Harvard, Cambridge, USA
3Laboratory of Genomic Diversity, National Cancer Institute, Frederick, USA
4Massachusetts General Hospital, Boston, USA
5Department of Preventive Medicine and Epidemiology, Loyola University Medical School, Maywood, USA
6Institute for Viral Disease Control and Prevention, Beijing, China
7The Institute Pasteur, Paris, France
8Harvard Medical School, Boston, USA;

Tóm tắt

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.

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