Genetic analysis of radiation-induced changes in human gene expression

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Abstract
We are regularly are exposed to radiation from environmental sources, and in medical procedures. To deal with radiation-induced damage, cells mount complex responses that rely on changes in gene expression. It has long been known that individuals vary in their sensitivity to radiation, and this variability is also seen at the gene expression level. Using radiation-induced changes in gene expression as quantitative traits, Smirnov et al. performed genetic linkage and association studies to map their regulators. The results provide new insights into the architecture of gene expression regulation in response to stress and have implications for basic and clinical understanding of how human cells respond to radiation. Humans are exposed to cell-damaging radiation from environmental and medical sources, causing cells to mount complex responses that rely on modifying gene expression. The regulators responsible for this are now mapped through genetic linkage and association studies, using radiation-induced changes in gene expression as quantitative traits and providing new insight into the architecture of gene expression regulation in response to stress. Humans are exposed to radiation through the environment and in medical settings. To deal with radiation-induced damage, cells mount complex responses that rely on changes in gene expression. These gene expression responses differ greatly between individuals1 and contribute to individual differences in response to radiation2. Here we identify regulators that influence expression levels of radiation-responsive genes. We treated radiation-induced changes in gene expression as quantitative phenotypes3,4, and conducted genetic linkage and association studies to map their regulators. For more than 1,200 of these phenotypes there was significant evidence of linkage to specific chromosomal regions. Nearly all of the regulators act in trans to influence the expression of their target genes; there are very few cis-acting regulators. Some of the trans-acting regulators are transcription factors, but others are genes that were not known to have a regulatory function in radiation response. These results have implications for our basic and clinical understanding of how human cells respond to radiation.