Genetic analysis of radiation-induced changes in human gene expression.
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 individuals and contribute to individual differences in response to radiation. Here we identify regulators that influence expression levels of radiation-responsive genes. We treated radiation-induced changes in gene expression as quantitative phenotypes, 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.
Howard Hughes Medical Institute, USA.
Denis A
DA
Smirnov
Michael
M
Morley
Eunice
E
Shin
Richard S
RS
Spielman
Vivian G
VG
Cheung
D000483:Alleles; D001402:B-Lymphocytes / Q000378:metabolism / Q000528:radiation effects; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002877:Chromosomes, Human / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D055785:Gene Knockdown Techniques; D008040:Genetic Linkage; D014644:Genetic Variation / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D005838:Genotype; D006801:Humans; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D043922:Toxicogenetics; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors; D020169:Caspases