Genetics of individual variation in response to radiation exposure

对辐射暴露反应的个体差异的遗传学

基本信息

批准号：
7289632
负责人：
Vivian G Cheung
金额：
$ 48.29万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2012-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): People are exposed to radiation through various sources. The use of radiation for diagnostic and therapeutic purposes is increasing. While these procedures bring significant benefits, radiation exposure carries risks. Prediction of risk from radiation exposure can be improved by taking into account the different biological effects of low and high dose radiation and individual variation in radiosensitivity. Most of the data on the effect of radiation have been accumulated from atomic bomb survivors, the only large cohort of exposed individuals that has been carefully monitored. Genetic study of radiosensitivity is difficult because relatives rarely get exposed to the same type and doses of radiation. In this project, we will use a combined genomic and genetic approach to determine the mechanisms of cellular response to different doses of radiation and to identify genetic variants that influence radiosensitivity. We will use expression level of genes in irradiated cells as phenotypes. This allows us to expose cells to different doses of radiation and to obtain radiation-induced phenotypes from related individuals for genetic analysis. The specific aims are 1) determine and compare the gene expression phenotypes induced by 0.5 Gy and 3 Gy IR, 2) map the chromosomal regions that influence inherited variation in IR responsive genes in large families by linkage analysis, and 3) confirm the linkage results and narrow the candidate gene regions by association analysis, and functionally characterize candidate regulators of response to 0.5 Gy and 3 Gy IR exposures. The results will provide information on the molecular and genetic basis of individual response to radiation exposure and form a foundation for a personalized approach to risk prediction.

描述（由申请人提供）：人们通过各种来源受到辐射。用于诊断和治疗目的的辐射的使用正在增加。虽然这些程序带来了显着的好处，但辐射暴露也带来了风险。通过考虑低剂量和高剂量辐射的不同生物效应以及放射敏感性的个体差异，可以改进对辐射暴露风险的预测。大多数关于辐射影响的数据都是从原子弹幸存者那里积累的，他们是唯一受到仔细监测的一大群受辐射个体。放射敏感性的遗传研究很困难，因为亲属很少接触相同类型和剂量的辐射。在这个项目中，我们将使用基因组和遗传学相结合的方法来确定细胞对不同剂量辐射的反应机制，并识别影响放射敏感性的遗传变异。我们将使用受辐射细胞中基因的表达水平作为表型。这使得我们能够将细胞暴露于不同剂量的辐射下，并从相关个体中获得辐射诱导的表型以进行遗传分析。具体目标是 1) 确定并比较 0.5 Gy 和 3 Gy IR 诱导的基因表达表型，2) 通过连锁分析绘制影响大家族中 IR 响应基因遗传变异的染色体区域，以及 3) 确认连锁结果并通过关联分析缩小候选基因区域，并在功能上表征对 0.5 Gy 和 3 Gy IR 暴露反应的候选调节因子。结果将提供有关个体对辐射暴露反应的分子和遗传基础的信息，并为个性化风险预测方法奠定基础。