| Project/Area Number |
16590261
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
IKEUCHI Tatsuro Tokyo Medical and Dental University, Medical Research Institute, Assoc.Prof. (90041839)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Kohtaro Tokyo Medical and Dental University, Medical Research Institute, Director (40000971)
YOSHIDA mitsuaki Tokyo Medical and Dental University, Medical, National Institute of Radiological Sciences, Section Chief (60182789)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Premature chromatid separation / PCS syndrome / Chromosomal instability / Aneuploid cells / BUB1B gene / Mitotic spindle checkpoint / Wilms tumor / Cancer prone genetic traait / 早期染色分体解離 / BUBR1遺伝子 / BubR1 / 高発がん性遺伝形質 / 分裂期チェックポイント / 染色体異数性 / トリソミー / 横紋筋肉腫 |
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| Research Abstract |
1. The PCS (premature chromatid separation) syndrome was established as a clinical entity (OMIM#176430) on the basis of our experiences in 7 Japanese families, being recognized to be a cancer-prone genetic trait due to the impairment of mitotic spindle checkpoint, or to the decreased expression of BUB1B-endoding protein (BubR1).
2. The frequency of cells in PCS is the most important hallmark for diagnosis of PCS syndrome. Hypotonic treatment of cells at 37℃ for 20 min was found to be most suitable among the conditions tested for the detection of PCS in individuals with the homozygous or heterozygous for the PCS trait.
3. Chromosomal and DNA polymorphic marker studies revealed that the tumors developing in PCS patients had uniparental (paternal) disomy (UPD) specifically for chromosome 11, suggesting that the increased dosage of imprinted genes such as paternally expressed IGF2 was primarily involved in tumor development.
4. Molecular analysis of BUB1B (encoding BubR1 protein) was performed in 7 Japanese families with PCS syndrome. In all the families studied, monoallelic BUB1B mutations were found : a single-base deletion in 4 families, and a splice site mutation, a nonsence mutation, and a missene mutation in one family each. Further analysis of haplotypes in the secomd alleles, where no mutations were detected, is now in progress.
5. Lymphoblastoid cell lines (LCLs) and fibroblasts derived from the two PCS patients and a number of LCLs from heterozygous carriers were established and stored.
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