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NK cell immunoglobulin-like receptor (KIR) haplotype-specific DNA fragments were sequenced to identify centromeric and telomeric allele-level haplotype structures and their frequencies from 76 unrelated individuals with European ancestry. Analysis was simplified by redefining the 5' boundary of the centromeric KIR gene cluster to include only exons 7-9 of KIR3DL3. Three consensus allele-level haplotypes were identified for a centromeric gene presence/absence structure designated as Cen-A1. KIR3DL3*00201 (exons 7-9)∼KIR2DL3*001∼KIR2DL1*00302 was the most frequent (37.5%) centromeric structure. Single consensus haplotypes were observed for haplotype structures Cen-B1 and Cen-B2. Six Tel-A1 and two Tel-B1 consensus haplotypes were observed; the most prevalent (23.0%) was KIR2DL4*00102∼KIR3DL1*002∼KIR2DS4*00101∼KIR3DL2*002. A small number of nucleotide substitutions (≤3) in the coding regions of the functional KIR genes created microvariants of the consensus haplotypes. Eight less common haplotype structures were also detected. Four carried hybrid genes formed during gene deletion events, two carried an insertion with a 2DL5/3DP1 fusion gene and two included a very large insertion. These data show that the KIR gene complex is composed of a limited number of conserved allele-level centromeric and telomeric haplotypes that have diversified by mutation, recombination within a locus and unequal crossing over.

Conserved KIR allele-level haplotypes are altered by microvariation in individuals with European ancestry