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The western Swedish BRCA1 founder mutation 3171ins5; a 3.7 cM conserved haplotype of today is a reminiscence of a 1500-year-old mutation.

Annika Bergman ; Zakaria Einbeigi ; Ulrica Olofsson (Institutionen för matematik, Matematisk statistik) ; Ziad Taib (Institutionen för matematik, Matematisk statistik) ; Arne Wallgren ; Per Karlsson ; Jan Wahlström ; Tommy Martinsson ; Margareta Nordling
European journal of human genetics : EJHG (1018-4813). Vol. 9 (2001), 10, p. 787-93.
[Artikel, refereegranskad vetenskaplig]

The most recurrent BRCA1/BRCA2 mutation in Sweden is the BRCA1 mutation 3171ins5. In the western part of Sweden this mutation accounts for as much as 77% of identified mutations in these two genes. Our aim was to analyse in detail the haplotype and founder effects of the 3171ins5 and furthermore attempt to estimate the time of origin of the mutation. In the study we included eighteen apparently unrelated families with hereditary breast and/or ovarian cancer. At least one individual in each family had previously tested positive for the 3171ins5 mutation. Polymorphic microsatellite markers were used for the haplotype analyses. The markers were located within or flanking the BRCA1 gene spanning a region of 17.3 cM. We found several different haplotypes both for disease alleles and for the normal alleles. However, a conserved haplotype of 3.7 cM was observed in the 3171ins5 carriers spanning over four markers located within or very close to the BRCA1 gene. As this haplotype was not present in any of the normal controls it is highly likely that this is a mutation identical by descent, i.e. a true founder. The results from the haplotype analyses were used to estimate the age of the mutation. Estimations based on the P(excess) and linkage disequilibrium gives a first appearance of the mutation sometime around the 6th century, approximately 50 generations ago.

Nyckelord: BRCA1 Protein, genetics, Breast Neoplasms, genetics, Conserved Sequence, genetics, DNA Mutational Analysis, Female, Founder Effect, Geography, Haplotypes, genetics, Humans, Male, Microsatellite Repeats, Mutagenesis, Insertional, genetics, Mutation, genetics, Pedigree, Sweden, Time Factors

Denna post skapades 2007-10-09. Senast ändrad 2011-01-20.
CPL Pubid: 52195


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Institutioner (Chalmers)

Institutionen för kvinnors och barns hälsa, Avdelningen för pediatrik (1991-2005)
Institutionen för särskilda specialiteter, Avdelningen för onkologi (1991-2005)
Institutionen för matematik, Matematisk statistik (1987-2001)



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