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The killer cell immunoglobulin-like receptor (KIR) genomic region: gene-order, haplotypes and allelic polymorphism

Journal

IMMUNOLOGICAL REVIEWS
Volume 190, Issue 1, Pages 40-52

Publisher

WILEY
DOI: 10.1034/j.1600-065X.2002.19004.x

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Funding

  1. NCI NIH HHS [P01CA23766] Funding Source: Medline
  2. NIAID NIH HHS [R01AI49245, U24AI49213] Funding Source: Medline

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Recent genetic studies have established that the killer cell immunoglobulin-like receptor (KIR) genomic region displays extensive diversity through variation in gene content and allelic polymorphism within individual KIR genes. It is demonstrated by family segregation analysis, genomic sequencing, and gene order determination that genomic diversity by gene content alone gives rise to more than 20 different KIR haplotypes and at least 40-50 KIR genotypes. In the most reductionist format, KIR haplotypes can be accommodated within one of 10 different prototypes, each with multiple permutations. Our haplotype model considers the KIR haplotype as two separate halves: the centromeric half bordered upstream by KIR3DL3 and downstream by 2DL4, and the telomeric half bordered upstream by 2DL4 and downstream by 3DL2. There are rare KIR haplotypes that do not fit into this model. Recombination, gene duplication, and inversion can however, readily explain these haplotypes. Additional allelic polymorphism imposes extensive individual variability. Accordingly, this segment of the human genome displays a level of diversity similar to the one observed for the human major histocompatibility complex. Recent application of immunogenetic analysis of KIR genes in patient populations implicates these genes as important genetic disease susceptibility factors.

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