Journal
AMERICAN JOURNAL OF HUMAN GENETICS
Volume 75, Issue 5, Pages 885-890Publisher
CELL PRESS
DOI: 10.1086/425221
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Funding
- NHGRI NIH HHS [R01 HG002386, HG02386] Funding Source: Medline
- NIEHS NIH HHS [R01 ES015733-01, R01 ES015733] Funding Source: Medline
- NIGMS NIH HHS [R01 GM070540, GM070540] Funding Source: Medline
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Studies have demonstrated that natural variation in the expression level of genes at baseline is extensive, and the determinants of this variation can be mapped by a genetic-linkage approach. In this study, we used lymphoblastoid cells to explore the variation in radiation-induced transcriptional changes. We found that, among normal individuals, there is extensive variation in transcriptional response to radiation exposure. By studying monozygotic twins, we demonstrated that there is evidence of a heritable component to this variation. The postradiation variation in the expression level of several genes, including the ferredoxin reductase gene (FDXR) and the cyclin-dependent kinase inhibitor 1A gene (CDKN1A), is significantly greater (P < .001) among twin pairs than within twin pairs. The induction of FDXR by radiation showed a bimodal distribution. Our findings have important implications for understanding the genetic basis of radiation response, which has remained largely unknown due to the lack of family material needed for genetic studies. Our approach, which uses expression phenotypes in cell lines, allows us to expose cells from family members to radiation. Similar study design can be applied to dissect the genetic basis of other complex human traits.
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