Τίτλος:
Haplotype analysis reveals that the recurrent BRCA1 deletion of exons 23 and 24 is a Greek founder mutation
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
A recurrent large genomic rearrangement (LGR) encompassing exons 23 and 24 of the BRCA1 gene has been identified in breast-ovarian cancer families of Greek origin. Its breakpoints have been determined as c.5406 + 664_*8273del11052 (RefSeq: NM_007294.3) and a diagnostic polymerase chain reaction (PCR) has been set up for rapid screening. In a series of 2,092 high-risk families completely screened for BRCA1 and BRCA2 germline mutations, we have found the deletion in 35 families (1.68%), representing 7.83% of the mutations identified in both genes and 10.3% of the total BRCA1 mutations. In order to characterize this deletion as a founder mutation, haplotype analysis was conducted in 60 carriers from 35 families, using three BRCA1 intragenic microsatellite markers and four markers surrounding the BRCA1 locus. Our results demonstrate a common shared core disease-associated haplotype of 2.89Mb. Our calculations estimate that the deletion has originated from a common ancestor 1450 years ago, which most probably inhabited the Asia Minor area. The particular (LGR) is the third mutation of such type that is proven to have a Greek founder effect in the Greek population, illustrating the necessity for LGRs testing in individuals of Greek descent. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Συγγραφείς:
Apostolou, P.
Pertesi, M.
Aleporou-Marinou, V.
Dimitrakakis, C.
Papadimitriou, C.
Razis, E.
Christodoulou, C.
Fountzilas, G.
Yannoukakos, D.
Konstantopoulou, I.
Fostira, F.
Περιοδικό:
Application of Clinical Genetics
Εκδότης:
Wiley-Blackwell Publishing Ltd
Λέξεις-κλειδιά:
BRCA1 protein; genomic DNA; BRCA1 protein; BRCA1 protein, human; BRCA2 protein; BRCA2 protein, human, adult; age determination; aged; Article; breast cancer; controlled study; exon; female; founder effect; gene deletion; gene frequency; gene locus; genetic susceptibility; germline mutation; Greece; haplotype; human; major clinical study; microsatellite marker; ovary cancer; polymerase chain reaction; priority journal; Sanger sequencing; breast tumor; gene deletion; genetic predisposition; genetic screening; genetics; haplotype; middle aged; Ovarian Neoplasms; pathology; pedigree, Adult; Aged; BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Female; Founder Effect; Genetic Predisposition to Disease; Genetic Testing; Germ-Line Mutation; Greece; Haplotypes; Humans; Middle Aged; Ovarian Neoplasms; Pedigree; Sequence Deletion
