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

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/7289632
• 关键词: Accounting; Biological; Candidate Disease Gene; Cells; Data; Diagnostic; Dose; Environment; Family; Foundations; Gene Expression; Genes; Genetic; Genetic Determinism; Genomics; Human; Individual; Inherited; Ionizing radiation; Maps; Medical; Molecular Genetics; Monitor; Phenotype; Population; Procedures; Purpose; Radiation; Radiation Tolerance; Range; Relative (related person); Risk; Source; Survivors; Therapeutic; Variant; base; cohort; genetic analysis; genetic linkage analysis; genetic variant; improved; radiation effect; response

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）： 人们通过各种来源暴露于辐射。辐射用于诊断和治疗目的的使用正在增加。尽管这些程序带来了重大的好处，但辐射暴露会带来风险。通过考虑到低剂量辐射的不同生物学作用以及辐射敏感性变化的不同生物学作用，可以改善辐射暴露风险的预测。关于辐射效应的大多数数据都是从原子弹幸存者那里积累的，原子弹幸存者是唯一经过仔细监测的大量暴露的个体。放射敏感性的遗传研究很困难，因为亲戚很少暴露于相同类型和剂量的辐射。在这个项目中，我们将使用一种组合的基因组和遗传方法来确定细胞对不同剂量辐射的反应的机制，并确定影响辐射敏感性的遗传变异。我们将使用辐照细胞中基因的表达水平作为表型。这使我们能够将细胞暴露于不同剂量的辐射，并从相关个体中获得辐射诱导的表型进行遗传分析。具体目的是1）确定和比较由0.5 Gy和3 Gy IR诱导的基因表达表型，2）映射染色体区域，这些区域影响大型家族中IR反应性基因的遗传变异的染色体区域，以及3）通过链接结果和3）确认链接结果，并通过关联分析和候选候选者的响应范围和0.5 Gy构成候选基因区域，并范围缩小候选基因区域的范围。结果将提供有关个人对辐射暴露的反应的分子和遗传基础的信息，并为个性化的风险预测方法构成基础。