Duplication, mutation and recombination of the human orphan gene KIR2DS3 contribute to the diversity of KIR haplotypes

被引:36
作者
Ordonez, D. [1 ]
Meenagh, A. [2 ]
Gomez-Lozano, N. [1 ]
Castano, J. [1 ]
Middleton, D. [2 ]
Vilches, C. [1 ]
机构
[1] Hosp Univ Puerta Hierro, Serv Inmunol, Madrid 28035, Spain
[2] Belfast City Hosp, No Ireland Reg Histocompatibil & Immunogenet Lab, Belfast BT9 7AD, Antrim, North Ireland
关键词
gene duplications; innate immunity; NK cell receptors; orphan genes;
D O I
10.1038/gene.2008.34
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The KIR2DS3 gene is an activating homologue of the inhibitory killer-cell immunoglobulin-like receptors (KIR) that recognize HLA-C molecules, enabling NK cells to survey the normal function of endogenous antigen presentation. The genetics of KIR2DS3 is complicated by the existence of alleles with similar coding sequences that map to different regions of the KIR complex in chromosome 19, or whose location in this complex is unknown. Here, by studying the family segregation of the KIR alleles 2DS3*001, *002 and *003N, and the distribution of these in unrelated individuals, we demonstrate the existence of two paralogous KIR2DS3 genes that can be inherited separately or, as it happens frequently in Caucasoids due to linkage disequilibrium, together. Each KIR2DS3 gene is almost invariably associated in its 50 end to a different copy of KIR2DL5, a gene previously shown to be duplicated in humans. KIR2DL5 and KIR2DS3 thus form two highly homologous gene clusters situated in the centromeric and the telomeric intervals of KIR haplotypes. Recombination between those clusters is the likely origin of new haplotypes, characterized in this study, which harbour further duplications or deletions of multiple KIR genes. Our results help understand the genetics of KIR2DS3 and the diversity of human KIR genotypes.
引用
收藏
页码:431 / 437
页数:7
相关论文
共 34 条
[31]   Investigation of killer cell immunoglobulinlike receptor gene diversity: I. KIR2DL4 [J].
Williams, F ;
Meenagh, A ;
Sleator, C ;
Middleton, D .
HUMAN IMMUNOLOGY, 2004, 65 (01) :31-38
[32]   Plasticity in the organization and sequences of human KIR/ILT gene families [J].
Wilson, MJ ;
Torkar, M ;
Haude, A ;
Milne, S ;
Jones, T ;
Sheer, D ;
Beck, S ;
Trowsdale, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (09) :4778-4783
[33]  
Winter CC, 1998, J IMMUNOL, V161, P571
[34]   Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function [J].
Yawata, M ;
Yawata, N ;
Draghi, M ;
Little, AM ;
Partheniou, F ;
Parham, P .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (03) :633-645