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Global diversity and evidence for coevolution of KIR and HLA

  1. Author:
    Single, R. M.
    Martin, M. P.
    Gao, X. J.
    Meyer, D. G.
    Yeager, M.
    Kidd, J. R.
    Kidd, K. K.
    Carrington, M.

  2. Author Address

    NCI, SAIC Frederick, Lab Genom Divers, Ft Detrick, MD 21702 USA. Univ Vermont, Dept Math & Stat, Burlington, VT 05405 USA. Univ Sao Paulo, Dept Genet & Biol Evolut, BR-05608900 Sao Paulo, SP, Brazil. NCI, SAIC Frederick Inc, Adv Technol Program, Core Genotyping Facil, Ft Detrick, MD 21702 USA. NCI, US Natl Inst Hlth, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.;Carrington, M, NCI, SAIC Frederick, Lab Genom Divers, Ft Detrick, MD 21702 USA.;carringt@ncifcrf.gov
    1. Year: 2007
    2. Date: Sep
  2. Journal: Nature Genetics
    1. 39
    2. 9
    3. Pages: 1114-1119
  4. Type of Article: Article
  5. ISSN: 1061-4036
  1. Abstract:

    The killer immunoglobulin- like receptor ( KIR) gene cluster shows extensive genetic diversity, as do the HLA class I loci, which encode ligands for KIR molecules. We genotyped 1,642 individuals from 30 geographically distinct populations to examine population- level evidence for coevolution of these two functionally related but unlinked gene clusters. We observed strong negative correlations between the presence of activating KIR genes and their corresponding HLA ligand groups across populations, especially KIR3DS1 and its putative HLA- B Bw4-80I ligands ( r=- 0.66, P 0.038). In contrast, we observed weak positive relationships between the various inhibitory KIR genes and their ligands. We observed a negative correlation between distance from East Africa and frequency of activating KIR genes and their corresponding ligands, suggesting a balance between selection on HLA and KIR loci. Most KIR- HLA genetic association studies indicate a primary influence of activating KIR- HLA genotypes in disease risk(1,2); concomitantly, activating receptor- ligand pairs in this study show the strongest signature of coevolution of these two complex genetic systems as compared with inhibitory receptor- ligand pairs.

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  2. DOI: 10.1038/ng2077
  3. View record in Web of Science®
  4. WOS: 000249122400021

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