OR44: KIR ALLELE AND HAPLOTYPE DIVERSITY OF MAORI AND POLYNESIANS

Aim Genetic variation of killer cell immunoglobulin-like receptors (KIR) diversifies human natural killer (NK) cell responses within and among individuals. With critical roles in immunity and reproduction, allotype variation affects how KIR molecules are expressed, interact with their HLA targets and transmit intracellular signals. Here we investigate KIR diversity at high resolution in the Maori and Polynesian populations. Methods Genomic DNA samples from 49 Māori (from New Zealand) and 34 Polynesians (from Cook Islands, Samoa and Tokelau) were drawn from the Victoria University of Wellington DNA Bank. In order to genotype the KIR locus at the allelic level, the DNA samples were amplified by PCR using KIR specific primers and sequenced by Pyrosequencing. Results Analyzing all 13 KIR genes we uncovered rich diversity in these populations. We identified a total of 80 KIR variants including four common newly-discovered alleles, and observed 35 centromeric and 22 telomeric KIR region haplotypes. This level of haplotypic diversity persisted even when non-expressed and synonymous KIR variants were not considered, and when analyzed in tandem with HLA class I every individual in each of the populations was unique. There was a mean of seven unique viable HLA-KIR interactions per individual. Conclusion In examining Māori and Polynesians we present one of the first population scale studies of KIR allele and haplotype variation. High KIR diversity is maintained through the entire locus both in Māori and Polynesians. Comparing with the few similar studies performed to date we show striking similarity between the worldwide dispersal of KIR and that of HLA; some of the alleles or haplotypes have a worldwide distribution and others are more localized geographically. Our findings reinforce the notion that sufficient NK cell diversity is critical to human survival, particularly as populations become exposed to new environments and evolving pathogens.