2000 Fiscal Year Final Research Report Summary
| Project/Area Number |
08283108
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (A)
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| Allocation Type | Single-year Grants |
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| Research Institution | National Cancer Center Research Institute |
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Principal Investigator |
OHKI Misao National Cancer Ctr. Res. Inst., Cancer Genomics Div., Chief, 腫瘍ゲノム解析・情報研究部, 部長 (00158792)
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| Co-Investigator(Kenkyū-buntansha) |
INOKO Hidetoshi Tokai Univ., School of Medicine, Prof., 医学部, 教授 (10101932)
SHIMIZU Nobuyoshi Keio Univ., School of Medicine, Prof., 医学部, 教授 (50162706)
SAKAKI Yoshiyuki The Institute of Meddical Science, The Univ. of Tokyo, Professor, 医科学研究所, 教授 (10112327)
NIIKAWA Norio Nagasaki Uuiv., School of Medicine, Prof., 医学部, 教授 (00111170)
ABE Tatsuo Kyoto Prefectural Univ., School of Medicine, Prof., 医学部, 教授 (60079746)
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| Project Period (FY) |
1996 – 2000
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| Keywords | Chromosome 21 / Chromosome 22 / Chromosome 11 / Whole Sequence / Hereditary defness DFNB8 / B10 / Early onset ataxia / Endometrial Cancer / SCAN method |
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| Research Abstract |
A Complete Notl restriction map of the long arm of chromosome 11 which spans more than 80 Mb long was constructed. Some members supported by this grant contributed largely to determining the sequence and gene catalog of the long arms of chromosome 21 and 22 as members of international consortia. One of the above members determined draft sequences of chromosome 11 and 18 totaling about 180 Mb. The other sequencing team member identified that TMPRSS3 encoding membrane spanning protease is the hereditary defness gene DFNB8/B10. The gene loci for early onset ataxia with hypoalbuminemia and familial essential myoclonus and epilepsy were determined by genetic analysis and we succeeded in identifying regions to show strong linkage disequilibrium. Molecular cloning of the breakpoint region of t(5;8)(q35;q24.1)found in a Sotos syndrome patient led to the identification of the Sotos1 gene which might be causative for Sotos syndrome. Six megabase region of 11q23 has been suggested to contain tumo
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r suppressor gene(s) for breast, lung, endometrial cancers and neuroblastoma by previous LOH analyzes. Construction of transcription map identified 59 genes within the region. Somatic mutations were found in one of these in lung and endometrial cancers suggesting that the relevant gene is a tumor suppressor. One megabase region of 6q21 and 100 kb region of 10q25-q26 are candidate regions to show the presence of tumor suppressor genes for pancreatic cancer, respectively. Sequence analysis of the region was recently completed. Gene expression profiles of 7,000 genes in response to gamma-radiation was analyzed by a SAGE method and data-base was constructed. Characterization of human artificial chromosomes revealed that alfoid DNA larger than 70 kb allows to form chromatin structure specific for centromere. Computer-assisted technology system to assemble raw sequence data from full length cDNA, to find sequence errors, and to change to more reliable sequence of proteins was established. Spectral color banding which distinguishes between Guimsa stained bands by different colors was developed. This allows to identify breakpoints of chromosome translocations at the level of G-band which are not resolved by conventional SKY methods. PLACE SSCP method to use multichannel capillary electrophoresis was established by developing suitable matrix material and computer software. Less
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