Complete sequence and gene map of a human major histocompatibility complex

Here we report the first complete sequence and gene map of a human major hi stocompatibility complex (MHC), a region on chromosome 6 which is essential to the immune system (reviewed in ref. 1). When it was discovered over 50 years ago the region was thought to specify histocompatibility genes, but t heir nature has been resolved only in the last two decades. Although many o f 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 i mmune system function. Over 50% of the MHC has been sequenced twice, in dif ferent haplotypes, giving insight into the extraordinary polymorphism and e volution of this region. Several genes, particularly of the MHC class II an d III regions, can be traced by sequence similarity and synteny to over 700 million years ago, dearly predating the emergence of the adaptive immune s ystem some 400 million years ago. The sequence is expected to be invaluable for the identification of many common disease loci. In the past, the searc h for these loci has been hampered by the complexity of high gene density a nd linkage disequilibrium.