Haplotype analysis in Icelandic and Finnish BRCA2 999del5 breast cancer families
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1120930
- author
- organization
- publishing date
- 2001
- type
- Contribution to journal
- 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
- pmid:11781689
- ISSN
- 1476-5438
- DOI
- 10.1038/sj.ejhg.5200717
- language
- English
- LU publication?
- yes
- id
- f024a172-a81b-4db3-bc54-a883be3f44d9 (old id 1120930)
- date added to LUP
- 2016-04-01 12:21:41
- date last changed
- 2022-01-27 02:43:05
@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}}, keywords = {{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}}, doi = {{10.1038/sj.ejhg.5200717}}, volume = {{9}}, year = {{2001}}, }