The western Swedish BRCA1 founder mutation 3171ins5; a 3.7 cM conserved haplotype of today is a reminiscence of a 1500-year-old mutation.
Artikel i vetenskaplig tidskrift, 2001

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.

Insertional

genetics

Mutagenesis

Pedigree

Time Factors

DNA Mutational Analysis

Microsatellite Repeats

Male

Geography

Female

Mutation

Breast Neoplasms

genetics

Sweden

Founder Effect

genetics

genetics

Haplotypes

genetics

genetics

BRCA1 Protein

Conserved Sequence

Humans

Författare

Annika Bergman

Göteborgs universitet

Zakaria Einbeigi

Göteborgs universitet

Ulrica Olofsson

Institutionen för matematik, Matematisk statistik

Göteborgs universitet

Ziad Taib

Göteborgs universitet

Institutionen för matematik, Matematisk statistik

Arne Wallgren

Göteborgs universitet

Per Karlsson

Göteborgs universitet

Jan Wahlström

Göteborgs universitet

Tommy Martinsson

Göteborgs universitet

Margareta Nordling

Göteborgs universitet

European Journal of Human Genetics

1018-4813 (ISSN)

Vol. 9 787-93

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1038/sj.ejhg.5200704