| Co-Investigator(Kenkyū-buntansha) |
NEI Masatoshi The Pennsylvania State University, Institute of Molecular Evolutionary Genetics, 教授
OHNO Susumu Beckman Research Institute of the City of Hope, Eternal Researcher, 終身研究員
BECK Stephan The Sanger Center Human Chromosome 6 Sequencing Group, Senior Ground Leader, Senior Gro
TROWSDALE John Cambridge University, Department.of Immunology, Professor, Professor
ANDO Asako Tokai University School of Medicine, Assistant Professor, 医学部, 講師 (40101935)
大野 進 米国ベックマン研究所, 終身研究員
TILANUS Marc University Hospital Utrecht Department o, 教授
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1997: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Research Abstract |
In order to clarify the gene organization of four paralogous regions ; chromosome 6p21.3 (HLA region), the 1q21-q25, 9q33-q34, and 19p13.1-p13.3 regions, and understanding of the evolution of the HLA region, we have analyzed the genomic structure of the HLA class I region, 9q33-q34 and 1q22-q23 region around the CD1 genes by YAC, PAC and BAC clones. The genomic sequence of the 1.8 megabase (Mb) HLA class I entire region, was determined by the shot gun method. In total, 124 genes or candidate gene sequences and 758 microsatellite repeats were found in this region. In addition, the five pair segments which showed high sequence homology to each other were found in the HLA class I region, suggesting that segmental genome duplication must have occurred during the evolution of the human MHC, ln the 9q33-q34 region, three genes which have homologous genes in the HLA region were mapped, HXB -C5 -GRP78 from PCR analyses of the YAC clones, In the 1q22-q23 region, an approximately 1.8 Mb YAC and PAC contig containing thefive CD1 genes were constructed by PCR using locus-specific and STS primer pairs and sequencing of the end regions of PAC clones. Ten genes were located in the telomeric side of CDlE with the order of SPTA 1 - MNDA -FYI - IFI-16 -FCERIA -KRTC7 -CRP -CRPP1 -ARCS - KIAAO 120 . Further, from PCR analyses of the YAC clones which were located on the telomeric side of KIAA 0120, twelve genes were mapped, (ATP1A2 - PXF - CBP -AIM2)- LYAM - (CD48 - LY9 - PPOX) -USF1 - (EAT2 -PBX1) - ALDH9 - RXRG - POU2F1 -CD3Z - ATAC - (FV- ELAM1 - LNHR) -FMO1 - FASL between D1S1705 and WI-6210. Thus, it was revealed that the 1q22-q23 region around the CD1 genes contained a cluster of genes which had immunological importance, such as SPTA 1, FY, IFI-16, ECERIA, ARCS, LYAM, CD48, LY9, SCM, CD3Z, ATAC, ELAM1, LNHR and FASL .
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