A mutation in Emphasis Type="Italic"KIR3DS1/Emp

Authors: Maureen P Martin Véronique Pascal Meredith Yeager John Phair Gregory D Kirk Keith Hoots Stephen J O’Brien Stephen K Anderson Mary Carrington

Publish Date: 2007/08/09

Volume: 59, Issue: 10, Pages: 823-829

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Abstract

The KIR gene cluster exhibits a high degree of polymorphism in terms of gene content as well as allelic polymorphism and data suggest that it is evolving rapidly The KIR3DL1 locus is one of the most polymorphic loci within this cluster and is unique in that it encodes an activating receptor KIR3DS1 as well as multiple inhibitory KIR3DL1 allotypes Because KIR3DS1 has been implicated in a number of diseases we tested for the presence of KIR3DS1 variants that might affect its expression and activating capacity Preliminary FACS analysis indicated that indeed some individuals with the KIR3DS1 allele showed no cell surface expression of the molecule Sequencing analysis identified a variant with a complex deletion/substitution mutation in exon 4 which encodes the D1 extracellular domain resulting in a premature stop codon We subsequently genotyped 3960 unrelated individuals and determined the frequencies of this allele across geographically distinct world populations The data indicate that the null KIR3DS1 allele is uncommon arose on a single haplotype and spread across geographically distinct populationsThis project has been funded in whole or in part with federal funds from the National Cancer Institute National Institutes of Health under contract N01CO12400 The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names commercial products or organizations imply endorsement by the US government This research was supported in part by the Intramural Research Program of the NIH National Cancer Institute Center for Cancer Research

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