Naslov
Computational Analysis of Novel BRCA1 and BRCA2 Genes Unclassified Sequence Variants Found in Healthy Females in Croatia

Autori
Ozretić, Petar ; Musani, Vesna ; Sabol, Maja ; Car, Diana ; Levanat, Sonja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the 35th FEBS Congress / The FEBS Journal 277 (s1) / Perham, Richard - Oxford : Wiley-Blackwell, 2010, 18-18

Skup
The 35th FEBS Congress

Mjesto i datum
Göteborg, Švedska, 26.06.2010. - 01.07.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
BRCA1 ; BRCA2 ; in silico ; UVs ; mutations ; polymorphisms ; Croatia

Sažetak
BRCA1 (breast cancer 1 gene) and BRCA2 (breast cancer 2 gene) are the major hereditary breast/ovarian cancer predisposing genes and their mutations increase the risk of developing cancer. Almost half of all BRCA1 and BRCA2 sequence variants found are unclassified variants (UVs) so their clinical significance is unknown or uncertain. That represents problem for risk assessment in genetic counseling. We have developed method for detection of inherited predisposition to breast/ovarian cancer and analyzed occurrence and distribution of BRCA1 and BRCA2 sequence variants on 220 healthy women in Croatia. The aim of this study was to identify UVs that may have deleterious effects on intronic or exonic splicing, protein structure and function, and protein functional domains using in silico methods. Using different computational tools, we have found that two nonsynonymous amino acid changes and one single amino acid deletion potentially have no impact on structure and function of BRCA2 protein. Two synonymous amino acid changes could have impact on splicing regulation by disrupting and creating exonic splicing enhancers. Our only intronic UV showed no potential impact on splicing, because nucleotide changing at that position likely makes no changes in consensus splice sites. All other exonic UVs do not lead to creation of potential cryptic splice sites. In silico methods present fast and cheap method for assessing preliminary clinical significance, especially in cases with low frequent and ethnic specific alleles, when it is difficult to make population based studies and when expensive in vitro functional assays must be performed to assess functional effect of found sequence variants.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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