Abstract
DNA-repair pathways are critical for maintaining the integrity of the genetic material by protecting against mutations due to exposure-induced damages or replication errors. Polymorphisms in the corresponding genes may be relevant in genetic epidemiology by modifying individual cancer susceptibility or therapeutic response. We report data on the population distribution of potentially functional variants in XRCC1, APEX1, ERCC2, ERCC4, hMLH1, and hMSH3 genes among groups representing individuals of European, Middle Eastern, African, Southeast Asian and North American descent. The data indicate little interpopulation differentiation in some of these polymorphisms and typical F ST values ranging from 10 to 17% at others. Low F ST was observed in APEX1 and hMSH3 exon 23 in spite of their relatively high minor allele frequencies, which could suggest the effect of balancing selection. In XRCC1, hMSH3 exon 21 and hMLH1 Africa clusters either with Middle East and Europe or with Southeast Asia, which could be related to the demographic history of human populations, whereby human migrations and genetic drift rather than selection would account for the observed differences.
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Acknowledgements
We are grateful to our colleagues who shared samples from their collections and to all individuals who kindly consented to provide DNA for this study. We thank Chantal Richer, Hugues Sinnett, Patrick Beaulieu, and Vania Yotova for their assistance, and Dominika Kozubska for secretarial help. MK and DS are scholars of the Fonds de la Recherche en Santé du Québec, whereas GM and CM were recipients of studentships from the Fondation Hôpital Ste-Justine/Power Corporation Inc., and the Natural Sciences and Engineering Research Council, respectively. This work was supported by the Fondation Charles-Bruneau and, in part, by a research grant from the Canadian Institutes of Health Research to DL (MOP-12782).
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Mathonnet, G., Labuda, D., Meloche, C. et al. Variable continental distribution of polymorphisms in the coding regions of DNA-repair genes. J Hum Genet 48, 659–664 (2003). https://doi.org/10.1007/s10038-003-0097-0
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DOI: https://doi.org/10.1007/s10038-003-0097-0
