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PMID: 15185041 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

SNP haplotypes and allele frequencies show evidence for disruptive and balancing selection in the human leukocyte receptor complex.

Immunogenetics ·Vol. 56 ·No. 4 ·2004-07-00 ·Pages 225-37

Norman PJ, Cook MA, Carey BS, Carrington CV, Verity DH, Hameed K, Ramdath DD, Chandanayingyong D, Leppert M, Stephens HA, Vaughan RW

Abstract

The human leukocyte receptor complex (LRC) of Chromosome 19q13.4 encodes polymorphic and highly homologous genes that are expressed by cells of the immune system and regulate their function. There is an enormous diversity at the LRC, most particularly the variable number of killer cell immunoglobulin-like receptor (KIR) genes. KIR have been associated with several disease processes due to their interaction with polymorphic human leukocyte antigen class I molecules. We have assessed haplotype compositions, linkage disequilibrium patterns and allele frequencies in two Caucasoid population samples (n=54, n=100), using a composite of single-nucleotide polymorphism (SNP) markers and high-resolution, allele-specific molecular genotyping. Particular KIR loci segregated with SNP and other markers, forming two blocks that were separated by a region with a greater history of recombination. The KIR haplotype composition and allele frequency distributions were consistent with KIR having been subject to balancing selection (Watterson's F: P=0.001). In contrast, there was a high inter-population heterogeneity measure for the LRC-encoded leukocyte immunoglobulin-like receptor A3 (LILRA3), indicating pathogen-driven disruptive selection (Wright's FST=0.32). An assessment of seven populations representative of African, Asian and Caucasoid ethnic groups (total n=593) provided little evidence for long-range LRC haplotypes. The different natural selection pressures acting on each locus may have contributed to a lack of linkage disequilibrium between them.

MeSH Terms
Chromosomes, Human, Pair 19/genetics Gene Frequency Genetic Variation Genetics, Population Genotype Haplotypes/genetics Humans Killer Cells, Natural/immunology Leukocytes/immunology Linkage Disequilibrium Microsatellite Repeats Polymorphism, Single Nucleotide Receptors, Immunologic/genetics,immunology Selection, Genetic United Kingdom/ethnology Whites
Chemicals
Receptors, Immunologic
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Norman Paul J
Clinical Transplantation Laboratory, Guy's Hospital, 3rd Floor New Guy's House, St. Thomas' Street, London, SE1 9RT, UK. paul.norman@stanford.edu
Cook Mark A
Carey B Sean
Carrington Christine V F
Verity David H
Hameed Kamran
Ramdath D Dan
Chandanayingyong Dasnayanee
Leppert Mark
Stephens Henry A F
Vaughan R W
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Article Info
Journal
Immunogenetics
Abbr.
Immunogenetics
ISSN
0093-7711
DOI
10.1007/s00251-004-0674-1
Email
paul.norman@stanford.edu
Published
2004-07-00
Epub
2004-00-05
Pages
225-37
Language
English
Region
United States
NLM ID
0420404
Subset
IM
Grants
NCRR NIH HHS · M01-RR00064 · United States
External Links
PubMed source DOI: 10.1007/s00251-004-0674-1 View journal details
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