Co-Investigator(Kenkyū-buntansha) |
HIYAMA Keiko Hiroshima University, Division of Clinical and Experimental Oncology, Research Institute for Radiation Biology and Medicine, Associate Professor, 原爆放射線医科学研究所・ゲノム疾患治療研究部門, 助教授 (60253069)
HIYAMA Eiso Hiroshima University, Natural Science Center for Basic Research and Development, Professor, 自然科学研究支援開発センター・生命科学研究支援分野・生命医科学研究開発部, 教授 (00218744)
KODAIRA Mieko Radiation Effects Research Foundation, Department of Genetics, Assistant Senior Scientist, 遺伝学部, 副主任研究員 (60344412)
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Budget Amount *help |
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2003: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2002: ¥5,500,000 (Direct Cost: ¥5,500,000)
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Research Abstract |
Studying the genetic effects of A-bomb radiation in humans, i.e., he effects of A-bomb radiation on human germ cells, is very important for the establishment of radiation protection standards and for other purposes. We therefore introduced to our laboratory a microarray CGH method, one of the most effective techniques for studying the above. In the research supported by the Grant-in-Aid, we have completed work for satisfying basic requirements in the effective use of array CGH : (1)establishment of experiment conditions for accurately detecting large deletions, (2)expedited identification of increased or decreased genome copy numbers by means of computer image analyses, and (3)development ant improvement of computer software for management of voluminous data. Thus, it has become clear that, with the microarray technique, for which improvements have been made at our laboratory, radiation-induced deletion-type variations as large as noe million base pairs (1 Mb) or more can be quickly an
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d reliably identified. We selected about 2,400 Bac clones located on autosomes at an interval of 1.2 million base pairs (1.2 Mb), and printed them on three glass slides. Using the microarray, we conducted a population study for genome DNA obtained from 30 children of A-bomb survivors and 30 children of the control group, and identified two different types of variants in two individuals. A study of these individuals' parents showed that these variants were inherited from at least one of the parents. Apart from the population study, we analyzed the genomes from radiation-exposed cells using the array, and identified deletion-type variants in several sites. Using the above as a model, we established experiment conditions for determining the size of variant sites using quantitative PCR and quantitative Southern analysis. Thus, it was possible to speedily characterize the variants identified in the process of the population study. By conducting analysis using the current technique on an expanded study population, it is now possible to, for the first time, clarify transgenerational effects (genetic effects) of radiation in humans, whih had previously been possible only in animal models. Less
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