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Duplication, mutation and recombination of the human orphan gene KIR2DS3 contribute to the diversity of KIR haplotypes

Genes & Immunity volume 9, pages 431–437 (2008)Cite this article

Abstract

The KIR2DS3 gene is an activating homologue of the inhibitory killer-cell immunoglobulin-like receptors (KIR) that recognize HLA-C molecules, enabling NK cells to survey the normal function of endogenous antigen presentation. The genetics of KIR2DS3 is complicated by the existence of alleles with similar coding sequences that map to different regions of the KIR complex in chromosome 19, or whose location in this complex is unknown. Here, by studying the family segregation of the KIR alleles 2DS3*001, *002 and *003N, and the distribution of these in unrelated individuals, we demonstrate the existence of two paralogous KIR2DS3 genes that can be inherited separately or, as it happens frequently in Caucasoids due to linkage disequilibrium, together. Each KIR2DS3 gene is almost invariably associated in its 5′ end to a different copy of KIR2DL5, a gene previously shown to be duplicated in humans. KIR2DL5 and KIR2DS3 thus form two highly homologous gene clusters situated in the centromeric and the telomeric intervals of KIR haplotypes. Recombination between those clusters is the likely origin of new haplotypes, characterized in this study, which harbour further duplications or deletions of multiple KIR genes. Our results help understand the genetics of KIR2DS3 and the diversity of human KIR genotypes.

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Abbreviations

KIR:

killer-cell Ig-like receptor

LD:

linkage disequilibrium

SSOP:

sequence-specific oligonucleotide probe

SSP:

sequence-specific primer

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Acknowledgements

This work was supported by grant BFU2005–04622 from the Spanish Ministerio de Educación y Ciencia (to CV).

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Authors and Affiliations

  1. Servicio de Inmunología, Hospital Universitario Puerta de Hierro, Madrid, Spain

    D Ordóñez, N Gómez-Lozano, J Castaño & C Vilches

  2. Northern Ireland Regional Histocompatibility and Immunogenetics Laboratory, Belfast City Hospital, Belfast, UK

    A Meenagh & D Middleton

Authors
  1. D Ordóñez
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  2. A Meenagh
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  3. N Gómez-Lozano
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  4. J Castaño
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  5. D Middleton
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  6. C Vilches
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Corresponding author

Correspondence to C Vilches.

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The authors have no financial or commercial conflicts of interest.

Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Ordóñez, D., Meenagh, A., Gómez-Lozano, N. et al. Duplication, mutation and recombination of the human orphan gene KIR2DS3 contribute to the diversity of KIR haplotypes. Genes Immun 9, 431–437 (2008). https://doi.org/10.1038/gene.2008.34

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