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Haplotype analysis reveals that the recurrent BRCA1 deletion of exons 23 and 24 is a Greek founder mutation
Author(s) -
Apostolou P.,
Pertesi M.,
AleporouMarinou V.,
Dimitrakakis C.,
Papadimitriou C.,
Razis E.,
Christodoulou C.,
Fountzilas G.,
Yannoukakos D.,
Konstantopoulou I.,
Fostira F.
Publication year - 2017
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12824
Subject(s) - haplotype , genetics , exon , mutation , biology , founder effect , gene , allele
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.