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Genome-wide Linkage Scan Reveals Three Putative Breast-Cancer-Susceptibility Loci
- Source :
- The American Journal of Human Genetics. 84:115-122
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- Despite all the research efforts made during the last few decades, most of the cases of families with breast cancer remain unexplained. Mutations in BRCA1 and BRCA2, and in other breast-cancer-susceptibility genes, account for about 25% of familial breast cancer. Linkage studies have failed to identify other breast-cancer-susceptibility genes. The selection criteria of the families, differences in the population background, or clinical and genetic heterogeneity, among other factors, might determine the power to detect the linkage signal. We have performed a SNP-based linkage scan with a total of 6000 SNP markers across the genome in 41 breast-cancer Spanish families, with an average of four breast-cancer cases per family not associated with BRCA1 or BRCA2 germline mutations. In addition, we have included three BRCA-positive families to test the power in linkage detection from a low-complexity family in which a high-penetrance mutation segregates. We have identified three regions of interest, located on 3q25, 6q24, and 21q22. The two former regions showed a suggestive linkage signal (HLOD scores 3.01 and 2.26, respectively), and the latter region showed a significant linkage signal (HLOD score 3.55). Moreover, we found that a subset of 13 families with bilateral breast cancer presented a HLOD of 3.13 on the 3q25 region. Our results suggest that several variables must be taken into account before performing a linkage study in familial breast cancer because of the high heterogeneity within non-BRCA1/2 families. Phenotypic and geographic homogeneity could be the most important factors.
- Subjects :
- Genetic Markers
Male
Chromosomes, Human, Pair 21
Genes, BRCA2
Population
Genes, BRCA1
Breast Neoplasms
Single-nucleotide polymorphism
Biology
Functional Laterality
Article
Breast cancer
Germline mutation
Genetic linkage
Genetics
medicine
Humans
Genetics(clinical)
Family
Genetic Predisposition to Disease
skin and connective tissue diseases
education
Germ-Line Mutation
Genetics (clinical)
education.field_of_study
Genome, Human
Genetic heterogeneity
Chromosome Mapping
Cancer
Middle Aged
medicine.disease
Pedigree
Chromosomes, Human, Pair 6
Female
Chromosomes, Human, Pair 3
Breast disease
Subjects
Details
- ISSN :
- 00029297
- Volume :
- 84
- Database :
- OpenAIRE
- Journal :
- The American Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....0f1918a811575342ee638884bd7303f8