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

Barkardottir, Rosa B; Sarantaus, Laura; Arason, Adalgeir; Vehmanen, Paula; Bendahl, Pär-Ola LU ; Kainu, Tommi; Syrjakoski, Kirsi; Krahe, Ralf; Huusko, Pia and Pyrhonen, Seppo, et al. (2001) In European Journal of Human Genetics 9(10). p.773-779
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... (More)
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. (Less)
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publication status
published
subject
keywords
mutation age estimation, hereditary breast cancer, BRCA2, Founder mutation
in
European Journal of Human Genetics
volume
9
issue
10
pages
773 - 779
publisher
Nature Publishing Group
external identifiers
  • pmid:11781689
  • scopus:0034747772
ISSN
1476-5438
DOI
10.1038/sj.ejhg.5200717
language
English
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yes
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f024a172-a81b-4db3-bc54-a883be3f44d9 (old id 1120930)
date added to LUP
2008-06-24 12:36:49
date last changed
2018-02-18 03:45:21
@article{f024a172-a81b-4db3-bc54-a883be3f44d9,
  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.},
  author       = {Barkardottir, Rosa B and Sarantaus, Laura and Arason, Adalgeir and Vehmanen, Paula and Bendahl, Pär-Ola and Kainu, Tommi and Syrjakoski, Kirsi and Krahe, Ralf and Huusko, Pia and Pyrhonen, Seppo and Holli, Kaija and Kallioniemi, Olli-P and Egilsson, Valgardur and Kere, Juha and Nevanlinna, Heli},
  issn         = {1476-5438},
  keyword      = {mutation age estimation,hereditary breast cancer,BRCA2,Founder mutation},
  language     = {eng},
  number       = {10},
  pages        = {773--779},
  publisher    = {Nature Publishing Group},
  series       = {European Journal of Human Genetics},
  title        = {Haplotype analysis in Icelandic and Finnish BRCA2 999del5 breast cancer families},
  url          = {http://dx.doi.org/10.1038/sj.ejhg.5200717},
  volume       = {9},
  year         = {2001},
}