Genome sequencing analysis of the 1.8 Mb entire human MHC class I region

The human MHC class I region spans 1.8 Mb from the MICB gene to the HLA-F gene at the telomeric end of the HLA region. There are fewer genes recognized in this region than in the class II or class III region, probably because this region remained uncharacterized for genomic organization. Based on the 1,796,938 bp genomic sequence of the entire class I region determined in our laboratory, the complete gene structure of this region has finally emerged. This region embraces as many as 118 genes (73 known and 45 new genes) with a gene density of one gene every 15.2 kb, which is comparable to that of the gene-rich class III region. The GC content is fairly uniform throughout the class I region, being 45.8% on average, which corresponds to the isochore H1. By investigation of genetic polymorphisms in 26 out of 758 microsatellite repeats identified in the class I region, we could reduce the critical region for Behçet's disease (associated with B51) and psoriasis vulgaris (associated with Cw6) to approximately 50 kb segments, between MICA and HLA-B and between TCF19 and S, respectively. Thus, systematic large-scale genomic sequencing provides an efficient way of identifying genes and of mapping disease-susceptible genes in the genome.