Project/Area Number |
11236204
|
Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
|
Research Institution | The University of Tokyo |
Principal Investigator |
FUKAMACHI Shoji (2003) The University of Tokyo, Graduate School of Frontier Sciences, Research Associate, 大学院・新領域創成科学研究科, 助手 (20323446)
嶋 昭紘 (1999-2002) 東京大学, 大学院・新領域創成科学研究科, 教授 (60011590)
|
Co-Investigator(Kenkyū-buntansha) |
SHIMA Akihiro The University of Tokyo, Graduate School of Frontier Sciences, Professor Emeritus, 大学院・新領域創成科学研究科, 名誉教授 (60011590)
|
Project Period (FY) |
1999 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
|
Budget Amount *help |
¥93,200,000 (Direct Cost: ¥93,200,000)
Fiscal Year 2003: ¥21,300,000 (Direct Cost: ¥21,300,000)
Fiscal Year 2002: ¥21,300,000 (Direct Cost: ¥21,300,000)
Fiscal Year 2001: ¥23,900,000 (Direct Cost: ¥23,900,000)
Fiscal Year 2000: ¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1999: ¥18,800,000 (Direct Cost: ¥18,800,000)
|
Keywords | cells / medaka / mechanism for maintaining of genome stability / apoptosis / p53 / 自然突然変異 / 色素細胞 / ポジショナルクローニング / γ-rays / Medaka fish / Speruatogenesis / MBT / Expression of paternal genome / Polymorphism / 生殖細胞突然変異 / 特定座位法 / 自然突然変異率 / 精原細胞 / 細胞死 / P53 / ESTマーカー / 父性発現 / TUNEL陽性細胞 / チェックポイント / p53遺伝子 / ATM遺伝子 / メダカ生殖細胞突然変異 / 雄生殖細胞 / 精原幹細胞 / 分化型精原細胞 / 高感受性集団 / 低線量 / 胚死 |
Research Abstract |
Germ-cell mutations caused in an organism are the source of genetic variation that is required for evolution, but at the same time, they may accumulate deleterious traits within a species. We have measured spontaneous germ-cell mutation rate at the pigmentation loci of the Medaka The resulting value was about 8×10^<-6>/locus/generation, indicating that vertebrate species share a common level of germ-cell mutation rate. Based on g-irradiation study, apoptosis of early differentiating spermatogonia with DNA damage proved to have an important role for regulation of overall mutation rate in male germ cells. In contrast mutation rate in female germ cells appeared to depend on fidelity of DNA repair. Next we found that spontaneous chromosomal breakages. and deletions are frequently caused in female germ cells of the Niigata wild population. Detailed analyses suggested that a novel mechanism for genome arrangement is involved in induction of germ-cell mutations in the wild populations of the Medaka Furthermore, we analysed the spectrum of spontaneous mutations by identifying spontaneous body-colour mutants. We positionally cloned responsible genes for the b, ci and i-3 mutants and identified they are caused by inversion, duplication or deletion of from several to dozens of nucleotides. Though others reported only insertions of transposon-like elements as a cause of spontaneous mutations on medaka genes (i, el, and rs-3), it is proved that that is not only the case. Meanwhile, because we isolated three pigmentation genes (functions of two of them are newly revealed by this study), we could provide new insights for developmental and evolutional studies of pigment cells.
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