Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors
Open Access
- 4 September 2012
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 22 (10), 1845-1854
- https://doi.org/10.1101/gr.137976.112
Abstract
The KIR complex appears to be evolving rapidly in humans, and more than 50 different haplotypes have been described, ranging from four to 14 KIR loci. Previously it has been suggested that most KIR haplotypes consist of framework genes, present in all individuals, which bracket a variable number of other genes. We used a new technique to type 793 families from the United Kingdom and United States for both the presence/absence of all individual KIR genes as well as copy number and found that KIR haplotypes are even more complex. It is striking that all KIR loci are subject to copy number variation (CNV), including the so-called framework genes, but CNV is much more frequent in KIR B haplotypes than KIR A haplotypes. These two basic KIR haplotype groups, A and B, appear to be following different evolutionary trajectories. Despite the great diversity, there are 11 common haplotypes, derived by reciprocal recombination near KIR2DL4, which collectively account for 94% of KIR haplotypes determined in Caucasian samples. These haplotypes could be derived from combinations of just three centromeic and two telomeric motifs, simplifying disease analysis for these haplotypes. The remaining 6% of haplotypes displayed novel examples of expansion and contraction of numbers of loci. Conventional KIR typing misses much of this additional complexity, with important implications for studying the genetics of disease association with KIR that can now be explored by CNV analysis.Keywords
This publication has 32 references indexed in Scilit:
- The silent KIR3DP1 gene (CD158c) is transcribed and might encode a secreted receptor in a minority of humans, in whom the KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1 genes are duplicatedEuropean Journal of Immunology, 2004
- HLA and NK Cell Inhibitory Receptor Genes in Resolving Hepatitis C Virus InfectionScience, 2004
- Cutting Edge: Expansion of the KIR Locus by Unequal Crossing OverThe Journal of Immunology, 2003
- Recognition of HLA‐G by the NK cell receptor KIR2DL4 is not essential for human reproductionEuropean Journal of Immunology, 2003
- Killer Ig-Like Receptor Haplotype Analysis by Gene Content: Evidence for Genomic Diversity with a Minimum of Six Basic Framework Haplotypes, Each with Multiple SubsetsPublished by The American Association of Immunologists ,2002
- Some human KIR haplotypes contain two KIR2DL5 genes: KIR2DL5A and KIR2DL5BImmunogenetics, 2002
- Reciprocal crossover asymmetry and meiotic drive in a human recombination hot spotNature Genetics, 2002
- Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populationsGenes & Immunity, 2002
- Intensely punctate meiotic recombination in the class II region of the major histocompatibility complexNature Genetics, 2001
- Plasticity in the organization and sequences of human KIR/ILT gene familiesProceedings of the National Academy of Sciences of the United States of America, 2000