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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES015733-05
Application #
8118274
Study Section
Special Emphasis Panel (ZES1-LWJ-E (CG))
Program Officer
Mcallister, Kimberly A
Project Start
2007-08-01
Project End
2011-10-31
Budget Start
2011-06-01
Budget End
2011-10-31
Support Year
5
Fiscal Year
2011
Total Cost
$156,797
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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