Linkage disequilibrium and haplotype blocks in the MHC vary in an HLA haplotype specific manner assessed mainly by DRB1*03 and DRB1*04 haplotypes
Linkage disequilibrium and haplotype blocks in the MHC vary in an HLA haplotype specific manner assessed mainly by DRB1*03 and DRB1*04 haplotypes
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DOI：
10.1038/sj.gene.6364272
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发表时间：
2006-03-01
影响因子：
5
通讯作者：
Lie, BA
中科院分区：
文献类型：
--
作者：
Blomhoff, A;Olsson, M;Lie, BA
第一代连锁不平衡（LD）和人类主要组织相容性复合体（MHC）的单倍型图谱已经产生，以帮助解开许多疾病易感基因在这个地区提供了第一套单倍型tagSNPs。几个参数，如研究的群体，使用的标记图，多态性的密度和应用的算法，影响单倍型块的外观和标签的选择。MHC包含有限数量的祖先保守单倍型。我们通过研究DR-DQ单倍型，主要是那些携带DRB 1 * 03和DRB 1 * 04等位基因的单倍型，解决了潜在的HLA单倍型对LD模式，单倍型块和标签选择在整个扩展MHC（xMHC）的影响。我们观察到在不同HLA背景下计算的LD的程度和范围有显著差异，以及所定义的单倍型和所选标签的大小和边界的变化。我们的研究结果表明，潜在的祖先HLA单倍型结构是另一个参数，以考虑构建LD地图的xMHC。这可能是必不可少的疾病易感基因的映射，因为许多疾病与特定的HLA单倍型相关并映射。
First generation linkage disequilibrium (LD) and haplotype maps of the human major histocompatibility complex (MHC) have been generated in order to aid the unraveling of the numerous disease predisposing genes in this region by offering a first set of haplotype tagSNPs. Several parameters, like the population studied, the marker map used, the density of polymorphisms and the applied algorithm, are influencing the appearance of haplotype blocks and selection of tags. The MHC comprises a limited number of ancestral, conserved haplotypes. We address the impact of the underlying HLA haplotypes on the LD patterns, haplotype blocks and tag selection throughout the entire extended MHC (xMHC) by studying DR-DQ haplotypes, mainly those carrying DRB1* 03 and DRB1* 04 alleles. We observed significantly different degree and extent of LD calculated on different HLA backgrounds, as well as variation in the size and boundaries of the defined haplotype and tags selected. Our results demonstrate that the underlying ancestral HLA haplotypic architecture is yet another parameter to take into consideration when constructing LD maps of the xMHC. This may be essential for mapping of disease susceptibility genes since many diseases are associated with and map on particular HLA haplotypes.