TY - JOUR
T1 - On the origin and diffusion of BRCA1 c.5266dupC (5382insC) in European populations
AU - Hamel, Nancy
AU - Feng, Bing-Jian
AU - Foretova, Lenka
AU - Stoppa-Lyonnet, Dominique
AU - Narod, Steven A
AU - Imyanitov, Evgeny
AU - Sinilnikova, Olga
AU - Tihomirova, Laima
AU - Lubinski, Jan
AU - Gronwald, Jacek
AU - Gorski, Bohdan
AU - Hansen, Thomas v O
AU - Nielsen, Finn C
AU - Thomassen, Mads
AU - Yannoukakos, Drakoulis
AU - Konstantopoulou, Irene
AU - Zajac, Vladimir
AU - Ciernikova, Sona
AU - Couch, Fergus J
AU - Greenwood, Celia M T
AU - Goldgar, David E
AU - Foulkes, William D
N1 - © 2011 Macmillan Publishers Limited All rights reserved 1018-4813/11
PY - 2011/3
Y1 - 2011/3
N2 - 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.
AB - 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.
U2 - http://dx.doi.org/10.1038/ejhg.2010.203
DO - http://dx.doi.org/10.1038/ejhg.2010.203
M3 - Journal article
SN - 1018-4813
VL - 19
SP - 300
EP - 306
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 3
ER -