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ESTABLISHMENT OF A 1.8 MB SEQUENCE DRAFT OF FELINE MHC (FLA) CLASS I REGION AND COMPARATIVE SEQUENCE ANALYSIS OF CLASS I REGION BETWEEN HLA AND FLA.
Naoya Yuhki Ph.D. , Thomas Beck Ph.D. , Sabrina Selway , Robert Stephens Ph.D. and Stephen J. O
Brien, Ph.D. . Frederick MD, National Cancer Institute, 21701-1201, Laboratory of Genomic Diversity and Frederick MD, SAIC at Frederick, 21701-1201, Advanced Biomedical Computing Center .
A 1.8 Mb sequence draft was established by shotgun sequencing of twenty BAC clones in the domestic cat MHC class I region. GENSCAN analysis predicted forty framework genes plus twenty class I genes/gene fragments in this region, spanning from BAT1 to olfactory receptor genes. Most of framework genes in the feline MHC class I region have orthologous gene contents and similar gene orders as those of human HLA, indicating that framework structures in feline and human class I regions are well maintained. Eighteen class I genes/gene fragments of 20 class I genes were found between BAT1 and Oct3 genes, occupying approximately 450 kb region, while remaining 2 class I gene/gene fragment were found between HSR1 and RNF23 genes in the feline MHC class I region. These two class I regions appear to be orthologous to human HLA-B, -C and HLA-E region, respectively. However, these class I regions in the domestic cat maintained multiple and also unique 20 Kb gene duplication units each containing a class I gene plus a partial sequence of BAT1 gene. Since this unit structure was not recognized in any other MHC class I system so far reported, we propose that species-specific convergent gene duplications play a role in the genesis of MHC class I regions. No class I genes were found between MOG and HTEX4 genes in the feline class I region, where eleven class I genes/gene fragments are located as HLA-A region in human HLA, indicating that the entire HLA-A class I region was deleted in the feline MHC class I region.