Recombinant structures expand and contract inter and intragenic diversification at the KIR locus

Abstract

BackgroundThe human KIR genes are arranged in at least six major gene-content haplotypes, all of which are combinations of four centromeric and two telomeric motifs. Several less frequent or minor haplotypes also exist, including insertions, deletions, and hybridization of KIR genes derived from the major haplotypes. These haplotype structures and their concomitant linkage disequilibrium among KIR genes suggest that more meaningful correlative data from studies of KIR genetics and complex disease may be achieved by measuring haplotypes of the KIR region in total.ResultsTowards that end, we developed a KIR haplotyping method that reports unambiguous combinations of KIR gene-content haplotypes, including both phase and copy number for each KIR. A total of 37 different gene content haplotypes were detected from 4,512 individuals and new sequence data was derived from haplotypes where the detailed structure was not previously available.ConclusionsThese new structures suggest a number of specific recombinant events during the course of KIR evolution, and add to an expanding diversity of potential new KIR haplotypes derived from gene duplication, deletion, and hybridization.

Skin Cancer Risk Is Modified by KIR/HLA Interactions That Influence the Activation of Natural Killer Immune Cells

“…(16). The KIR 2DL5-2DS3/2DS5 genic block was not used for haplotype assignment due to ambiguity of location.…”

“…Within each block are the ancestral haplotype A, and divergent B haplotypes with increasing diversity primarily of activating KIR genes (15). Novel KIR structural haplotypes arise from ongoing recombination and unequal crossover events (14, 16). …”

Genetic variation and the de novo assembly of human genomes

“…The assembly process is further complicated by extensive structural polymorphisms, which are enriched more than tenfold in these particular regions 1,39,40 . Different human haplotypes (that is, allelic variation) have been shown to vary by hundreds of kilobases owing to paralogous sequences that are present in different numbers of copies and in different orientations 8,40–42 . Therefore, inadvertent assembly of two structurally diverse haplotypes within these regions is more likely than in unique regions of the genome.…”

Genetic polymorphisms and association of KIR-HLA system of Chinese Henan Han population and an extensive KIR gene diversity study between populations distributed worldwide

“…Except for the genes described above, the centromeric region is considered to contain the KIR2DS2, 2DL2, 2DL3, 2DP1 and 2DL1; and the telomeric region is considered to contain KIR3DL1, 3DS1, 2DS1 and 2DS4. The KIR2DL3, 3DL1 and 2DS4 belong to A-motif genes; and the KIR2DS2, 2DL2, 3DS1, 2DS1, 2DS3, 2DS5, and 2DL5 belong to B-motif genes [6][7][8]. In our study, we also distinguished between the centromeric motif and the telomeric motif.…”