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Haplotype analysis in Icelandic and Finnish BRCA2 999del5 breast cancer families

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Authors
Barkardottir, RB
Sarantaus, L
Arason, A
Vehmanen, P
Bendahl, PO
Kainu, T
Syrjäkoski, K
Krahe, R
Huusko, P
Pyrhönen, S
Holli, K
Kallioniemi, OP
Egilsson, V
Kere, J
Nevanlinna, H
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Issue Date
2001-10-01

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Citation
Eur. J. Hum. Genet. 2001, 9(10):773-9
Abstract
The 999del5 mutation is the single, strong BRCA2 founder mutation in Iceland and the most common BRCA1/2 founder mutation in Finland. To evaluate the origin and time since spreading of the 999del5 mutation in Iceland and in Finland, we constructed haplotypes with polymorphic markers within and flanking the BRCA2 gene in a set of 18 Icelandic and 10 Finnish 999del5 breast cancer families. All Icelandic families analysed shared a common core haplotype of about 1.7 cM. The common ancestors for the Icelandic families studied were estimated to trace back to 340-1000 years, not excluding the possibility that the mutation was brought to Iceland during the settlement of the country. Analysis of the Finnish families revealed two distinct haplotypes. A rare one, found in three families in the old settlement region in southwestern Finland, shared a four-marker (0.5 cM) core haplotype with the Icelandic 999del5 haplotype. A distinct approximately 6 cM haplotype was shared by seven 999del5 Finnish families estimated to have a common ancestry 140-300 years ago. These families cluster in two geographical regions in Finland, in the very same area as those with the rare haplotype and also in the most eastern, late settlement region of Finland. The results may indicate a common ancient origin for the 999del5 mutation in Iceland and in Finland, but distinct mutational events cannot be ruled out. The surprising finding of the same mutation in two completely different haplotypes in a sparsely populated area in Finland may suggest gene conversion.
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http://dx.doi.org/10.1038/sj.ejhg.5200717
ae974a485f413a2113503eed53cd6c53
10.1038/sj.ejhg.5200717
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English Journal Articles (Peer Reviewed)

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