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

Authors

Paulo j. Norman, Guy’s Hospital,London
Mark A. Cook, University of Birmingham, UK
B. Sean Carey, UK
Christine V.F Carrington, University of the West Indies,Tobago
David H. Verity, St Thomas’ Hospital-King’s College,UK
Kamran Hamid, Aga Khan UniversityFollow
D. Dan Ramdath, University of the West Indies, Tobago
Dasnayanee Chandanayingyong,, Siriraj Hospital, Thailand
Mark Leppert,, University of Utah, USA
Henry A.F Stephens, University College, London.
R. W. R.W Vaughan, St. Thomas’ Street, UK

Document Type

Article

Department

Internal Medicine (East Africa)

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 F ST=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.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Springer Nature

Recommended Citation

Norman, P. J., Cook, M. A., Carey, B. S., Carrington, C. V., Verity, D. H., Hameed, K., ... & Vaughan, R. W. (2004). SNP haplotypes and allele frequencies show evidence for disruptive and balancing selection in the human leukocyte receptor complex. Immunogenetics, 56(4), 225-237.