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High KIR diversity in Amerindians is maintained using few gene-content haplotypes

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Abstract

Interaction between killer cell immunoglobulin-like receptors (KIR) and cognate HLA class I ligands influences the innate and adaptive immune response to infection. The KIR family varies in gene content and allelic polymorphism, thereby, distinguishing individuals and populations. KIR gene content was determined for 230 individuals from three Amerindian tribes from Venezuela: the Yucpa, Bari and Warao. Gene-content haplotypes could be assigned to 212 individuals (92%) because only five different haplotypes were present—group A and four group B. Six different haplotype combinations accounted for >80% of individuals. Each tribe has distinctive genotype frequencies. Despite few haplotypes, all 14 KIR genes are at high frequency in the three tribes, with the exception of 2DS3. Each population has an even frequency of group A and B haplotypes. Allele-level analysis of 3DL1/S1 distinguished five group A haplotypes and six group B haplotypes. The high frequency and divergence of the KIR haplotypes in the Amerindian tribes provide greater KIR diversity than is present in many larger populations. An extreme case being the Yucpa, for whom two gene-content haplotypes account for >90% of the population. These comprise the group A haplotype and a group B haplotype containing all the KIR genes, except 2DS3, that typify the group B haplotypes. Here is clear evidence for balancing selection on the KIR system and the biological importance of both A and B haplotypes for the survival of human populations.

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Acknowledgements

Our gratitude to the Yucpa, Bari, and Warao communities and to the Fundacion Zumaque for their help with the field work. This work was supported by a fellowship from the Lymphoma Research Foundation (PJN) and grants from the Leukemia and Lymphoma Society of the USA and the NIH (AI017892) (PP).

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Authors and Affiliations

  1. Department of Structural Biology, Stanford University School of Medicine, Sherman Fairchild Building, Stanford, CA, USA

    Ketevan Gendzekhadze, Paul J. Norman, Laurent Abi-Rached & Peter Parham

  2. Lab. Physiopathology, Experimental Medicine “Miguel Layrisse” Venezuelan Research Institute (IVIC), Caracas, Venezuela

    Ketevan Gendzekhadze & Zulay Layrisse

  3. Department of Structural Biology and Immunology and Microbiology, Stanford University, Stanford, CA, 94305, USA

    Peter Parham

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  1. Ketevan Gendzekhadze
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  2. Paul J. Norman
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  3. Laurent Abi-Rached
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  4. Zulay Layrisse
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  5. Peter Parham
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Fig. S1

Linkage Disequilibrium (LD) Parameters for pairs of KIR loci in Amerindians. LD for two-locus associations from unknown gametic phase calculated according to (Mattiuz et al, 1971). Δ - linkage disequilibrium parameter, r - relative linkage disequilibrium, h - two-locus haplotype frequency (≥0.02), p - observed vs expected haplotype frequency (Yates' test)

Fig. S2

Frequencies of HLA-B, C and KIR-HLA (ligand-receptor pairing) combinations in Amerindians (Yucpa and Bari)

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Gendzekhadze, K., Norman, P.J., Abi-Rached, L. et al. High KIR diversity in Amerindians is maintained using few gene-content haplotypes. Immunogenetics 58, 474–480 (2006). https://doi.org/10.1007/s00251-006-0108-3

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