Genetic analysis of radiation-induced changes in human gene expression.
Genetic analysis of radiation-induced changes in human gene expression.
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DOI：
10.1038/nature07940
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发表时间：
2009-05-28
期刊：
影响因子：
64.8
通讯作者：
Cheung VG
中科院分区：
文献类型：
--
作者：
Smirnov DA;Morley M;Shin E;Spielman RS;Cheung VG
人类通过环境和医疗环境暴露于辐射。为了应对辐射引起的损伤，细胞会产生复杂的反应，这些反应依赖于基因表达的变化。这些基因表达反应在个体之间差异很大，并导致个体对辐射反应的差异。在这里，我们确定的监管机构影响辐射响应基因的表达水平。我们处理辐射引起的基因表达的变化作为定量表型，并进行遗传连锁和关联研究，以映射其监管机构。对于超过1,200个这些表型有显着的证据表明，连锁特定的染色体区域。几乎所有的调节因子都以反式作用来影响其靶基因的表达;很少有顺式作用的调节因子。一些反式调节因子是转录因子，但另一些是不知道在辐射反应中具有调节功能的基因。这些结果对我们了解人体细胞对辐射的反应具有基础和临床意义。
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 transacting 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.
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通讯作者：
Sharp BM
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Kruglyak L
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