Study of Genetic effects of A-bomb radiation using microarray CGH

使用微阵列 CGH 研究原子弹辐射的遗传效应

• 批准号: 14380261
• 负责人: TAKAHASHI Norio
• 金额: $ 7.17万
• 依托单位: Radiation Effects Research Foundation
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14380261/
• 关键词: microarray; comparative genomic hybridization (CGH); radiation effects; transgenerational effects; polymorphic variants; human genome; deletion-type variants; マイクロアレイCGH; 被爆2世; 突然変異; 全ゲノム解析; 生殖細胞; Bac-クローンDNA; 集団遺伝調査

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 … More 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

研究原子弹辐射对人类的遗传影响，即，研究原子弹辐射对人体生殖细胞的影响，对于制定辐射防护标准和其他目的具有重要意义。因此，我们向我们的实验室介绍了微阵列CGH方法，这是研究上述问题的最有效技术之一。在本研究中，我们完成了以下工作，以满足有效使用阵列CGH的基本要求：（1）建立准确检测大缺失的实验条件，（2）通过计算机图像分析快速鉴定基因组拷贝数的增加或减少，以及（3）开发和改进用于管理大量数据的计算机软件。因此，很明显，利用我们实验室已经改进的微阵列技术，辐射诱导的缺失型变异大到1 Mb或更多，可以很快地检测到。 ...更多信息 d可靠识别。我们选择了大约2,400个位于常染色体上的Bac克隆，间隔为120万个碱基对（1.2 Mb），并将它们打印在三个载玻片上。使用微阵列，我们对从30名原子弹幸存者儿童和30名对照组儿童获得的基因组DNA进行了群体研究，并在两个个体中鉴定了两种不同类型的变异。对这些个体父母的研究表明，这些变异至少遗传自父母之一。除了群体研究之外，我们还使用阵列分析了来自辐射暴露细胞的基因组，并在几个位点鉴定了缺失型变体。以此为模型，建立了利用定量PCR和Southern定量分析确定变异位点大小的实验条件。因此，可以快速表征在群体研究过程中鉴定的变体。通过使用现有技术对扩大的研究人群进行分析，现在有可能首次澄清辐射对人类的跨代影响（遗传影响），而这在以前只能在动物模型中进行。少

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Sasaki M.: "Clinical Surveillance of surgical imipenem-resistant Pseudomonas aeruginosa infection in a Japanese hospital"Journal of Hospital Infection. 56. 111-118 (2004)

Sasaki M.：“日本医院外科亚胺培南耐药铜绿假单胞菌感染的临床监测”《医院感染杂志》。

Kodaira M.: "Genetic effects of atomic-bomb radiation : Analysis of minisatellite genes"JAERI (Japan Atomic Energy Research Institute). 15 (2002)

Kodaira M.：“原子弹辐射的遗传效应：小卫星基因分析”JAERI（日本原子能研究所）。

Kodaira M.: "Genetic effects of radiation : Effects on germline mutation rates at human minisatellite loci"Radiat Biol Res Commun. 37(3). 264-281 (2002)

Kodaira M.：“辐射的遗传效应：对人类小卫星位点种系突变率的影响”Radiat Biol Res Commun。

Kodaira M.: "Genetic effects of radiation : Human germline mutation rates at minisatellite loci"Nagasaki Med J. 77. 188-191 (2002)

Kodaira M.：“辐射的遗传效应：小卫星位点的人类种系突变率”Nagasaki Med J. 77. 188-191 (2002)

Hiyama K.: "Detection of telomerase activity in lung cancer tissues"Lung Cancer. 1,74. 401-412 (2003)

Hiyama K.：“肺癌组织中端粒酶活性的检测”肺癌。