| Project/Area Number |
06044201
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Tokai University School of Medicine |
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Principal Investigator |
INOKO Hidetoshi Tokai University School of Medicine, Professor, 医学部, 教授 (10101932)
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| Co-Investigator(Kenkyū-buntansha) |
BECK Stephan Imperial Cancer Research Fund, DNA Sequence Lab., Principal Scientist, 主任研究員
DAWKINS Roger University of Western Australia, Professor, 教授
GERAGHY Daniel Fred Huntchinson Cancer Research Center, Associate Professor, 助教授
TROWSDALE John Imperial Cancer Research Fund, Human Immuno-genetic Lab., Principal Scientist, 主任研究員
ANDO Asako Tokai University School of Medicine, Lecturer, 医学部, 講師 (40101935)
BECK Stephan Imperial Cancer Research Fund DNA Sequen, 主任研究員
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 1996: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1995: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1994: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | HLA region / gene organization / genomic sequencing / cDNA cloning / disease susceptible gene / polycystic kidney disease / salivary gland tumor / Behcet's disease / psoriasis vulgaris / 強直性脊椎炎 / 塩基配列解析 / 疾患原因遺伝子 / 発現遺伝子 / HLA / コスミドクローン / 多型性 / コスミドコンティグ / ホモロジー解析 / ショットガン法 / YACクローン / ショットガンシークエンシング |
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| Research Abstract |
Characterization of the human MHC region at the nucleotide level will provide an important information on the physical and gene organization of the human chromosome as a model system as well as the development of human diseases. In collaboration with ICRF,Sanger Institute, Western Australia University and Fred Hutchinson Cancer Research Center, we have cloned about 3,000kb area of the human MHC region and searched for new expressed genes by mouse gene probes, detection of CpG islands, cDNA isolation or genomic sequencing analysis.
On the centromeric side of the HLA class II region which corresponds to the mouse t complex region, 7 new genes were identified, HSET-HKE1.5-HKE2-HKE3-RING1-HKE6-HKE4-RXRb- from the centromeric side. HKE6 is a possible candidate gene for the development of polycystic kidney disease. An uncharacterized 450kb region harboring the junction between the class II and class III region was colned and so far, four genes, TN-X RAGE,HOX12 and Notch4 (a human homologue of the mouse int-3 gene belonging to a Notch family) were identified. Notch4 is a candidate gene responsible for the development of salivary gland tumor.
In order to elucidate the gene organization of the HLA class I region and to identify new genes involved in the development of HLA-class I associated diseases such as Behcet's disease and psoriasis vulgaris, cosmid clones covering the 452 kb region around the HLA-B and -C genes were determined for their nucleotide sequences. Homology and Grail search as well as RT-PCR,Northern hybridization and cDNA cloning analyzes revealed the existence of 21 genes (10 known genes and 11 new genes) and 7 EST-homologous segments. Further, 35 dinucleotide repeats, which will provide a powerful tool for precise mapping of the disease susceptible genes as polymorphic markers, we identified.
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