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Title: Germline mutation rate in the hypervariable minisatellite CEB1 in the parents of children with leukaemia
Authors: Davies, B.G.
Birch, J.M.
Eden, T.O.B.
Reeves, M.
Dubrova, Yuri E.
Taylor, G.M.
First Published: 27-Mar-2007
Publisher: Nature Publishing Group
Citation: British Journal of Cancer, 2007, 96, pp.1265-1271
Abstract: Gardner and colleagues advanced the hypothesis that the Seascale leukaemia cluster may have been caused by germ cell mutagenesis due parental preconceptional irradiation (PPI) of fathers working at the Sellafield nuclear installation. Recent evidence has shown that PPI can lead to an increased germline mutation rate in certain minisatellite loci, allowing previously undetectable levels of germline sensitivity to IR to be measured. In this study, we have investigated the hypothesis that childhood leukaemia may be associated with parental germ cell sensitivity detected by an increased parental germline minisatellite mutation rate. To test this we compared the germline mutation rate of the hypervariable minisatellite locus, CEB1 in family trios (both parents and their child) of children with leukaemia (n = 109) compared with normal families (n = 64). We found no significant difference in mean mutation rate of parents of children with leukaemia and control children (0.0414 vs 0.0887; P > 0.05). The majority of germline mutations (95%) were paternal, and unaffected by the presence of leukaemia cells in the sample. We found no significant differences in mean minisatellite allele size (72 vs 68 repeats; p > 0.05), or mutational spectrum (gains or losses of repeats) in the parents of case and control children. Although preliminary, our results suggest that childhood leukaemia is unlikely to be associated with increased germline minisatellite instability resulting from exposure of parental germ cells to mutagens such as IR.
Type: Article
Description: This is the authors' final version of the paper published as British Journal of Cancer, 2007, 96, pp. 1265-1271. The final published version is available from, DOI: 10.1038/sj.bjc.6603706
Appears in Collections:Published Articles, Dept. of Genetics

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