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

• Published in: BMC genomics Vol. 14; no. 1; p. 89
• Main Authors: Pyo, Chul-Woo, Wang, Ruihan, Vu, Quyen, Cereb, Nezih, Yang, Soo Young, Duh, Fuh-Mei, Wolinsky, Steven, Martin, Maureen P, Carrington, Mary, Geraghty, Daniel E
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08-02-2013; BioMed Central
• Subjects: Alleles; Autoimmune diseases; Cancer; Centromere - genetics; Chromosome deletion; Disease; Diversification; DNA sequencing; Experiments; Gene Duplication; Gene Frequency; Genes; Genetic aspects; Genetic recombination; Genetics; Genomics; Haplotypes; HIV; HLA Antigens - genetics; Human immunodeficiency virus; Humans; Immune system; Killer cells; Killer Cells, Natural - cytology; Killer Cells, Natural - metabolism; Ligands; Linkage Disequilibrium; Medical research; Medicine, Experimental; Methods; Nucleotide sequencing; Polymorphism, Single Nucleotide; Receptors, KIR - chemistry; Receptors, KIR - genetics; Studies; Telomere - genetics
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/1471-2164-14-89

The 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.
Towards 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.
These 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.