title: Of mice and (wo)men: genotype-phenotype correlations in BRCA1.
abstract: To date, over 6300 mutations in BRCA1, involving 1100 distinct sites, have been described and reported in the BIC (breast cancer information core) database. Since the first BRCA1 mutations in early-onset breast and ovarian cancer families were reported, several attempts to establish genotype-phenotype correlations for this gene have been reported. Moreover, in vitro data have suggested dominant-negative effects of putative mutant BRCA1 proteins over wild-type proteins. Genotype-phenotype correlations are not only important for predicting the clinical course of the disease and to allow tailor-made surveillance of individuals at risk, but also have implications for the elucidation of the molecular genetic mechanisms underlying BRCA1-mediated tumorigenesis and the development of gene transfer-based therapies. Here, we discuss genotype-phenotype correlations at the BRCA1 locus in mouse and man, and the functional aspects that may account for these observations.
authors.affiliation: MRC Human Genetics Unit, Edingburgh, UK. peter.hohenstein@hgu.mrc.ac.uk
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenstein
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; D012333:RNA, Messenger