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A BRCA2 mutation incorrectly mapped in the original BRCA2 reference sequence, is a common West Danish founder mutation disrupting mRNA splicing.
- Source :
-
Breast cancer research and treatment [Breast Cancer Res Treat] 2011 Jul; Vol. 128 (1), pp. 179-85. Date of Electronic Publication: 2010 Dec 24. - Publication Year :
- 2011
-
Abstract
- Inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose carriers to breast and ovarian cancer. The authors have identified a mutation in BRCA2, 7845+1G>A (c.7617+1G>A), not previously regarded as deleterious because of incorrect mapping of the splice junction in the originally published genomic reference sequence. This reference sequence is generally used in many laboratories and it maps the mutation 16 base pairs inside intron 15. However, according to the recent reference sequences the mutation is located in the consensus donor splice sequence. By reverse transcriptase analysis, loss of exon 15 in the final transcript interrupting the open reading frame was demonstrated. Furthermore, the mutation segregates with a cancer phenotype in 18 Danish families. By genetic analysis of more than 3,500 Danish breast/ovarian cancer risk families, the mutation was identified as the most common BRCA2 mutation in West Denmark, while it is rare in Central and East Denmark and not identified in South Sweden. Haplotype analysis using dense SNP arrays indicated a common founder of the mutation approximately 1,500 years ago.
- Subjects :
- Breast Neoplasms epidemiology
DNA Mutational Analysis
Denmark epidemiology
Female
Genes, BRCA1
Genetic Predisposition to Disease
Haplotypes
Humans
Likelihood Functions
Middle Aged
Mutation
Reference Values
Breast Neoplasms genetics
Genes, BRCA2
Polymorphism, Single Nucleotide
RNA Splice Sites genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7217
- Volume :
- 128
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Breast cancer research and treatment
- Publication Type :
- Academic Journal
- Accession number :
- 21184276
- Full Text :
- https://doi.org/10.1007/s10549-010-1272-6