Nature. 1999 Oct 28;401(6756):921-3. doi: 10.1038/44853.
Here we report the first complete sequence and gene map of a human major histocompatibility complex (MHC), a region on chromosome 6 which is essential to the immune system. When it was discovered over 50 years ago the region was thought to specify histocompatibility genes, but their nature has been resolved only in the last two decades. Although many of the 224 identified gene loci (128 predicted to be expressed) are still of unknown function, we estimate that about 40% of the expressed genes have immune system function. Over 50% of the MHC has been sequenced twice, in different haplotypes, giving insight into the extraordinary polymorphism and evolution of this region. Several genes, particularly of the MHC class II and III regions, can be traced by sequence similarity and synteny to over 700 million years ago, clearly predating the emergence of the adaptive immune system some 400 million years ago. The sequence is expected to be invaluable for the identification of many common disease loci. In the past, the search for these loci has been hampered by the complexity of high gene density and linkage disequilibrium.
我们在此报告人类主要组织相容性复合体（MHC）的首个完整序列和基因图谱，该复合体位于6号染色体上，对免疫系统至关重要。50多年前该区域被发现时，人们认为它指定了组织相容性基因，但直到最近二十年其本质才得以明确。尽管已鉴定出的224个基因座中许多（预计有128个会表达）的功能仍不明确，但我们估计约40%的已表达基因具有免疫系统功能。超过50%的MHC已在不同单倍型中进行了两次测序，这让我们得以深入了解该区域的非凡多态性和进化情况。通过序列相似性和共线性可以追溯到超过7亿年前的几个基因，尤其是MHC II类和III类区域的基因，这明显早于约4亿年前适应性免疫系统的出现。该序列预计对识别许多常见疾病基因座具有极高价值。过去，寻找这些基因座的工作因高基因密度和连锁不平衡的复杂性而受阻。
