Genomic characterization of two large Alu-mediated rearrangements of the BRCA1 gene

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Peixoto, A (Author) Other; Pinheiro, M (Author) Other; Massena, L (Author) Other; Santos, C (Author) Other; Pinto, P (Author) Other; Rocha, P (Author) Other; Pinto, C (Author) Other; Manuel R Teixeira (Author) ICBAS

Journal

Title: Journal of Human Genetics

Vol. 58

Pages: 78-83

ISSN: 1434-5161

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 21 Citations

Scopus - 22 Citations

Other information

Authenticus ID: P-005-341

DOI: 10.1038/jhg.2012.137

Abstract (EN): To determine whether a large genomic rearrangement is actually novel and to gain insight about the mutational mechanism responsible for its occurrence, molecular characterization with breakpoint identification is mandatory. We here report the characterization of two large deletions involving the BRCA1 gene. The first rearrangement harbored a 89 664-bp deletion comprising exon 7 of the BRCA1 gene to exon 11 of the NBR1 gene (c.441+1724_oNBR1:c.1073+480del). Two highly homologous Alu elements were found in the genomic sequences flanking the deletion breakpoints. Furthermore, a 20-bp overlapping sequence at the breakpoint junction was observed, suggesting that the most likely mechanism for the occurrence of this rearrangement was nonallelic homologous recombination. The second rearrangement fully characterized at the nucleotide level was a BRCA1 exons 11-15 deletion (c.671-319_4677-578delinsAlu). The case harbored a 23 363-bp deletion with an Alu element inserted at the breakpoints of the deleted region. As the Alu element inserted belongs to a still active AluY family, the observed rearrangement could be due to an insertion-mediated deletion mechanism caused by Alu retrotransposition. To conclude, we describe the breakpoints of two novel large deletions involving the BRCA1 gene and analysis of their genomic context allowed us to gain insight about the respective mutational mechanism. Journal of Human Genetics (2013) 58, 78-83; doi:10.1038/jhg.2012.137; published online 6 December 2012

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6