Abstract
The BRCA1 mutation c.5266dupC was originally described as a founder mutation in the Ashkenazi Jewish (AJ) population. However, this mutation is also present at appreciable frequency in several European countries, which raises intriguing questions about the origins of the mutation. We genotyped 245 carrier families from 14 different population groups (Russian, Latvian, Ukrainian, Czech, Slovak, Polish, Danish, Dutch, French, German, Italian, Greek, Brazilian and AJ) for seven microsatellite markers and confirmed that all mutation carriers share a common haplotype from a single founder individual. Using a maximum likelihood method that allows for both recombination and mutational events of marker loci, we estimated that the mutation arose some 1800 years ago in either Scandinavia or what is now northern Russia and subsequently spread to the various populations we genotyped during the following centuries, including the AJ population. Age estimates and the molecular evolution profile of the most common linked haplotype in the carrier populations studied further suggest that c.5266dupC likely entered the AJ gene pool in Poland approximately 400–500 years ago. Our results illustrate that (1) BRCA1 c.5266dupC originated from a single common ancestor and was a common European mutation long before becoming an AJ founder mutation and (2) the mutation is likely present in many additional European countries where genetic screening of BRCA1 may not yet be common practice.
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Acknowledgements
We would like to thank Dr Graham R Taylor for providing us with frequency and distribution information for the c.5266dupC mutation in England. This work was supported in part by Susan G Komen for the Cure (NH, WDF), by the Hellenic Cooperative Oncology Group research grant and the Greek General Secretariat for Research and Technology (GSRT) program (DY), as well as by the Russian Federation for Basic Research (grant 10-04-92601) and the Federal Agency for Science and Innovations (contract 02.740.11.0780) (EI). Genetic testing in the Czech Republic was supported by an MZ0 MOU 2005 grant (LF). We would also like to thank the Neye foundation for financial support (TOVH).
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Hamel, N., Feng, BJ., Foretova, L. et al. On the origin and diffusion of BRCA1 c.5266dupC (5382insC) in European populations. Eur J Hum Genet 19, 300–306 (2011). https://doi.org/10.1038/ejhg.2010.203
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DOI: https://doi.org/10.1038/ejhg.2010.203
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