Search for MHC-associated genes in human: five new genes centromeric to HLA-DP with yet unknown functions

Abstract

Taking advantage of five mouse genomic or cDNA probes [KE5(probe 14), KE4 (probe 11), KE3 (probe 7), KE2 (probe 5), and SET] mapped on the H-2K region in mouse, we have identified and localized homologues of these five genes in the human major histocompatibility complex region (HKE5, HKE4, HKE3, HKE2, and HSET, respectively). Cosmid cloning and pulsed field gel electrophoresis analyses indicated that a human homologous gene, HKE5, is located 10 kilobases (kb) centromeric of the alpha 2 (XI) collagen (COL11A2) gene followed by HKE4. HKE3, closely linked to HKE2, is located 170 kb centromeric of HKE4. Furthermore, HSET is located 50 kb centromeric of HKE2. This gene organization outside the DP subregion is completely identical to that of the mouse H-2K region centromeric of I-Pb3, a mouse homologue of the DPB gene, except the lack of genes corresponding to the H-2K and -K2 genes in human.

The Human COL11A2 Gene Structure Indicates that the Gene Has Not Evolved with the Genes for the Major Fibrillar Collagens

“…The human COL11A2 gene was obtained from two overlapping cosmid clones, 505-1 and 515, that were isolated in the course of searching the human major histocompatibility complex region (22). The presence of the COL11A2 gene in the clones was confirmed by Southern blot hy-* This work was supported in part by National Institutes of Health Grant AR-39740 and a grant from the Lucille P. Markey Charitable Trust.…”

Physical mapping of the retinoid X receptorB gene in mouse and human

“…Bacteriophage )~ clones hybridizing to the Rxrb probe were isolated from a genomic DNA library of 129/Sv female mouse liver (Stratagene, La Jolla, CA). Human cosmid clones in the HLA-DP subregion were isolated by cosmid walking and have been characterized previously (Janatipour et al 1992). …”

“…Previously, the genes homologous to the five human non-class II genes (i. e., RING1 through 5) were mapped in the mouse, and the homologs of three mouse non-class II genes (i. e., H2-Ke3, 4, and 5) were localized in the human HLA class II region (Hanson and Trowsdale 1991). Recently, the human homologs of the mouse genes Set, H2-Ke2, H2-Ke3, H2-Ke4, and H2-Ke5 were mapped immediately outside of the HLA-DP subregion, using cosmid cloning and pulsed field gel electrophoresis (Janatipour et al 1992). Based on these results, it has been established that the human genome retains the same gene organization just outside the HLA-DP subregion as that in the mouse H2-K region except that the class I genes are not found in the region but located more telomerically.…”

cDNA Cloning of the Human Homologues of the MouseKe4andKe6Genes at the Centromeric End of the Human MHC Region

“…Among these genes, the biological functions of three human homologues of the mouse genes, HKE2, HKE4, and HKE6, have remained unknown. It is interesting to note that (6); [6] human 15-hydroxyprostaglandin dehydrogenase (9); [7] human 11b-hydroxysteroid dehydrogenase enzyme (12); [8] rat 11b-hydroxysteroid dehydrogenase enzyme (2). A dash indicates an amino acid identical with that of pKE611.…”

“…HKE6 possesses remarkable amino line AKIBA randomly primed cDNA libraries were acid sequence conservation with several bacterial pro-screened with a 5.5-kb EcoRI human cosmid fragment teins with oxidoreductase function and also shows sig- (8) containing both the HKE4 and the HKE6 genes as a nificant homology with the two unique functional domains containing the nucleotide cofactor binding site and the consensus motif characteristic of the members of the superfamily of short-chain alcohol dehydrogenases such as human and rat steroid and prostaglandin dehydrogenases. ᭧ 1996 Academic Press, Inc.…”