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

• 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 cΜ. We found several different haplotypes both for disease alleles and for the normal alleles. However, a conserved haplotype of 3.7 cΜ 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 Pexcess and linkage disequilibrium gives a first appearance of the mutation sometime around the 6th century, approximately 50 generations ago.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

BRCA1 gene

Breast neoplasm

Founder effect

Haplotype

Ovarian neoplasm

BRCA1 protein

BRCA2 protein

microsatellite DNA

age

allele

article

breast cancer

clinical observation

controlled study

familial cancer

family

gene linkage disequilibrium

gene mutation

genetic conservation

genetic polymorphism

heterozygote

human

ovary cancer

phylogeny

priority journal

Sweden

time

Breast Neoplasms

Conserved Sequence

DNA Mutational Analysis

Female

Geography

Haplotypes

Humans

Male

Microsatellite Repeats

Mutagenesis

Insertional

Mutation

Pedigree

Time Factors

BRCA1 Protein

genetics

Breast Neoplasms

Conserved Sequence

DNA Mutational Analysis

Female

Founder Effect

Geography

Haplotypes

Humans

Male

Microsatellite Repeats

Mutagenesis

Insertional

Mutation

Pedigree

Sweden

Time Factors

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)