Vandiedonck Claire, Knight Julian C
Wellcome Trust Centre for Human Genetics (WTCHG), University of Oxford, Oxford, UK.
Brief Funct Genomic Proteomic. 2009 Sep;8(5):379-94. doi: 10.1093/bfgp/elp010. Epub 2009 May 25.
Since its discovery more than 50 years ago, the human Major Histocompatibility Complex (MHC) on chromosome 6p21.3 has been at the forefront of human genetic research. Here, we review from a historical perspective the major advances in our understanding of the nature and consequences of genetic variation which have involved the MHC, as well as highlighting likely future directions. As a consequence of its particular genomic structure, its remarkable polymorphism and its early implication in numerous diseases, the MHC has been considered as a model region for genomics, being the first substantial region to be sequenced and establishing fundamental concepts of linkage disequilibrium, haplotypic structure and meiotic recombination. Recently, the MHC became the first genomic region to be entirely re-sequenced for common haplotypes, while studies mapping gene expression phenotypes across the genome have strongly implicated variation in the MHC. This review shows how the MHC continues to provide new insights and remains in the vanguard of contemporary research in human genomics.
自50多年前被发现以来,位于6号染色体p21.3区域的人类主要组织相容性复合体(MHC)一直处于人类遗传学研究的前沿。在此,我们从历史角度回顾了我们对涉及MHC的遗传变异的性质和后果的理解方面的主要进展,并强调了可能的未来方向。由于其特殊的基因组结构、显著的多态性以及早期与众多疾病的关联,MHC被视为基因组学的一个模型区域,是第一个被测序的重要区域,并确立了连锁不平衡、单倍型结构和减数分裂重组的基本概念。最近,MHC成为第一个对常见单倍型进行全基因组重测序的基因组区域,而全基因组范围内绘制基因表达表型的研究强烈表明MHC存在变异。这篇综述展示了MHC如何继续提供新的见解,并仍然处于当代人类基因组学研究的前沿。