NUCLEOTIDE-SEQUENCE ANALYSIS OF THE HLA CLASS-I REGION SPANNING THE 237-KB SEGMENT AROUND THE HLA-B AND HLA-C GENES

To elucidate the detailed gene organization of the human leukocyte ant igen (HLA) class I region on chromosome 6, seven contiguous cosmid gen omic clones covering the 237-kb segment around the HLA-B and -C loci w ere subjected to DNA sequencing by the shotgun strategy to give a sing le contig of 236,822 bp from the MICA gene (58.2 kb centromeric of HLA -B) to 90.8 kb telomeric of HLA-C. This region was confirmed to contai n four known genes, MICA, HLA-17, HLA-B, and HLA-C, from centromere to telomere. Further, a new member of the P5 multicopy genes was found t o be about 1.3 kb upstream of the HLA-17 gene and designated P5-8. Fiv e novel genes designated NOB1-5 were identified by RT-PCR and Northern blot hybridization. In addition, two pseudogenes, dihydrofolate reduc tase pseudogene (DHFRP) and ribosomal protein L3 homologous gene (RPL3 -Hom), were also found in the vicinity of the HLA-B and -C genes, resp ectively. The two segments (about 40 kb) downstream of the HLA-B and H LA-C genes showed high sequence homology to each other, suggesting tha t segmental genome duplication including the major histocompatibility complex (MHC) class I gene must have occurred during the evolution of the MHC. (C) 1997 Academic Press.