Molecular genetics of the KIR gene complex

Basic Sciences

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Abstract

KIR genotyping has now been completed in the CEPH families. KIR2DL4 and KIR3DL1 have been subtyped by sequence analysis, and minimal subtyping of other KIR genes has been performed. Dr. Richard Single at the University of Vermont has begun analysis of the data. The CEPH KIR haplotype data has already been useful in our disease studies. For example, the results of the linkage disequilibrium analysis were recently utilized in our study of a melanoma cohort (see "Genetic effects of the major histocompatibility complex (MHC) and KIR locus on autoimmune disease and cancer" project). Genotyping of the 29 worldwide populations has also been completed and analysis is in progress. Thus far, sequencing of one unusual KIR haplotype has been completed. This is a very truncated haplotype composed of 4 genes, two of which are hybrids, suggesting that this haplotype likely occurred by unequal crossing over.In collaboration with Dr. Stephan Beck, we identified the ancestral KIR from which all other KIR genes throughout the primate order appear to have been derived, which we have termed KIR3DL0. We predict KIR3DL0 to encode a functional, inhibitory molecule in all primates except perhaps human where a frameshift mutation would prevent its cell surface expression. Expression of KIR3DL0 in rhesus monkey was demonstrated by cDNA cloning and quantitative measurement of KIR3DL0 was determined from an enriched population of natural killer cells.