title: Haplotype analysis of BRCA1 gene reveals a new gene rearrangement: characterization of a 19.9 KBP deletion.
abstract: Germ-line mutations in the BRCA1 gene cause hereditary predisposition to breast and ovarian cancer. BRCA1 and BRCA2 mutations account for about 40% of high-risk families. Mutation-screening methods generally focus on genomic DNA and are usually PCR based; they enable the detection of sequence alterations such as point mutations and small deletions and insertions. However, they do not allow the detection of partial or entire exon(s) loss, because the presence of the homologous allele results in a positive PCR signal, giving rise to a false-negative result. Identification of unusual haplotypes in patient samples by an expectation maximization algorithm has recently been suggested as a method for identifying hemizygous regions caused by large intragenic deletions. Using a similar approach, we identified a novel BRCA1 genomic rearrangement in a breast/ovarian cancer family negative at the first mutation screening; we detected a deletion encompassing exons 14-19, probably due to replication slippage between Alu sequences.
authors.affiliation: Section of Oncogenetics, Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, Transplants and New Technologies in Medicine, University of Pisa and University Hospital of Pisa, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Tancredi
authors.forename: Elisa
authors.initials: E
authors.lastname: Sensi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cipollini
authors.forename: Paolo
authors.initials: P
authors.lastname: Aretini
authors.forename: Grazia
authors.initials: G
authors.lastname: Lombardi
authors.forename: Claudio
authors.initials: C
authors.lastname: Di Cristofano
authors.forename: Silvano
authors.initials: S
authors.lastname: Presciuttini
authors.forename: Generoso
authors.initials: G
authors.lastname: Bevilacqua
authors.forename: Maria Adelaide
authors.initials: MA
authors.lastname: Caligo
mesh_terms: D020087:Alu Elements / Q000235:genetics; D017931:DNA Primers; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D015321:Gene Rearrangement / Q000235:genetics*; D019398:Genes, BRCA1; D005820:Genetic Testing / Q000379:methods*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers