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.
|Wang, Isabel X; Core, Leighton J; Kwak, Hojoong et al. (2014) RNA-DNA differences are generated in human cells within seconds after RNA exits polymerase II. Cell Rep 6:906-15|
|Cheung, Vivian G; Nayak, Renuka R; Wang, Isabel Xiaorong et al. (2010) Polymorphic cis- and trans-regulation of human gene expression. PLoS Biol 8:|
|Dombroski, Beth A; Nayak, Renuka R; Ewens, Kathryn G et al. (2010) Gene expression and genetic variation in response to endoplasmic reticulum stress in human cells. Am J Hum Genet 86:719-29|
|Krewski, Daniel; Acosta Jr, Daniel; Andersen, Melvin et al. (2010) Toxicity testing in the 21st century: a vision and a strategy. J Toxicol Environ Health B Crit Rev 13:51-138|
|Cheung, Vivian G; Spielman, Richard S (2009) Genetics of human gene expression: mapping DNA variants that influence gene expression. Nat Rev Genet 10:595-604|
|Nayak, Renuka R; Kearns, Michael; Spielman, Richard S et al. (2009) Coexpression network based on natural variation in human gene expression reveals gene interactions and functions. Genome Res 19:1953-62|
|Smirnov, Denis A; Morley, Michael; Shin, Eunice et al. (2009) Genetic analysis of radiation-induced changes in human gene expression. Nature 459:587-91|
|Cheung, Vivian G; Bruzel, Alan; Burdick, Joshua T et al. (2008) Monozygotic twins reveal germline contribution to allelic expression differences. Am J Hum Genet 82:1357-60|
|Wang, Xuting; Tomso, Daniel J; Chorley, Brian N et al. (2007) Identification of polymorphic antioxidant response elements in the human genome. Hum Mol Genet 16:1188-200|
|Spielman, Richard S; Bastone, Laurel A; Burdick, Joshua T et al. (2007) Common genetic variants account for differences in gene expression among ethnic groups. Nat Genet 39:226-31|
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