The human major histocompatibility complex: 42,221 bp of genomic sequence, high-density sequence-tagged site map, evolution, and polymorphism for HLA class I

We report the isolation and characterization of newly identified yeast artificial chromosome (YAC) and bacterial artificial chromosome (BAC) clones spanning the HLA class I region between HLA-C and HLA-E and of YACs extending telomeric of HLA-F. When included with previously characterized HLA class I YACs, a contiguous stretch of over 2.4 Mb pairs including the entire class I region has been isolated as a series of overlapping YAC and BAC clones. Evidence that the cloned DNA faithfully represents the source genomic DNA was obtained by extensive characterization of the YACs and by independent isolation of two or more overlapping YACs or BACs spanning the entire region. As a result of this work, over 80 unique sequence probes were identified, the majority of which were sequenced to yield 42,221 bp of new major histocompatibility complex (MHC)-derived sequence. Some of these data were reduced to sequenced tagged site primer sets, facilitating the isolation of all or nearly all of HLA class I from a variety of genomic libraries. The sequence data were analyzed for protein coding capacity and homology to existing expressed tagged sites and tested for conservation of sequences in other mammalian genomes. These results indicated that large portions of the HLA class I region are conserved among mammals. Measurements of polymorphism within non-HLA class I loci generated additional data pointing toward information of potential relevance to MHC-associated diseases. The combined data and clones presented here set the stage for the determination of the complete nucleotide sequence of HLA class I. (C) 1998 Academic Press.