A mutation in KIR3DS1 that results in truncation and lack of cell surface expression

被引：11
作者：
Martin M.P. [1 ]
Pascal V. [2 ]
Yeager M. [3 ,4 ]
Phair J. [5 ]
Kirk G.D. [6 ]
Hoots K. [5 ]
O'Brien S.J. [7 ]
Anderson S.K. [8 ]
Carrington M. [1 ]
机构：
[1] Laboratory of Genomic Diversity, SAIC-Frederick, Inc., NCI-Frederick, Frederick
[2] Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, Frederick
[3] Core Genotyping Facility, SAIC-Frederick, Inc., NCI-Frederick, Frederick
[4] Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville
[5] Department of Medicine, Northwestern University Medical School, Chicago
[6] Department of Epidemiology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore
[7] Laboratory of Genomic Diversity, National Cancer Institute, Frederick
[8] Laboratory of Experimental Immunology, SAIC-Frederick, Inc., NCI-Frederick, Frederick
来源：
Immunogenetics | 2007年 / 59卷 / 10期
基金：
美国国家卫生研究院;
关键词：
Cell surface expression; Human Genome Diversity Panel (HGDP); KIR expression; KIR gene polymorphism; KIR3DS/L1; locus; KIR3DS1; Truncation;
D O I：
10.1007/s00251-007-0240-8
中图分类号：
学科分类号：
摘要：
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 3,960 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 populations. © 2007 Springer-Verlag.
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页码：823 / 829
页数：6
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