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Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts
BACKGROUND: Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897790/ https://www.ncbi.nlm.nih.gov/pubmed/20507642 http://dx.doi.org/10.1186/1471-2350-11-80 |
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author | Whiley, Phillip J Pettigrew, Christopher A Brewster, Brooke L Walker, Logan C Spurdle, Amanda B Brown, Melissa A |
author_facet | Whiley, Phillip J Pettigrew, Christopher A Brewster, Brooke L Walker, Logan C Spurdle, Amanda B Brown, Melissa A |
author_sort | Whiley, Phillip J |
collection | PubMed |
description | BACKGROUND: Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction tools, although accurate prediction of aberrant splicing by unclassified variants affecting exonic splice enhancers (ESEs) remains a challenge. METHODS: This study used a combination of RT-PCR analysis and splicing reporter minigene assays to assess five unclassified variants in the BRCA2 gene that we had previously predicted to disrupt an ESE using bioinformatic approaches. RESULTS: Analysis of BRCA2 c.8308 G > A (p.Ala2770Thr) by mRNA analysis, and BRCA2 c.8962A > G (p.Ser2988Gly), BRCA2 c.8972G > A (p.Arg2991His), BRCA2 c.9172A > G (p.Ser3058Gly), and BRCA2 c.9213G > T (p.Glu3071Asp) by a minigene assay, revealed no evidence for aberrant splicing. CONCLUSIONS: These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein. |
format | Text |
id | pubmed-2897790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28977902010-07-07 Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts Whiley, Phillip J Pettigrew, Christopher A Brewster, Brooke L Walker, Logan C Spurdle, Amanda B Brown, Melissa A BMC Med Genet Research Article BACKGROUND: Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction tools, although accurate prediction of aberrant splicing by unclassified variants affecting exonic splice enhancers (ESEs) remains a challenge. METHODS: This study used a combination of RT-PCR analysis and splicing reporter minigene assays to assess five unclassified variants in the BRCA2 gene that we had previously predicted to disrupt an ESE using bioinformatic approaches. RESULTS: Analysis of BRCA2 c.8308 G > A (p.Ala2770Thr) by mRNA analysis, and BRCA2 c.8962A > G (p.Ser2988Gly), BRCA2 c.8972G > A (p.Arg2991His), BRCA2 c.9172A > G (p.Ser3058Gly), and BRCA2 c.9213G > T (p.Glu3071Asp) by a minigene assay, revealed no evidence for aberrant splicing. CONCLUSIONS: These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein. BioMed Central 2010-05-28 /pmc/articles/PMC2897790/ /pubmed/20507642 http://dx.doi.org/10.1186/1471-2350-11-80 Text en Copyright ©2010 Whiley et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Whiley, Phillip J Pettigrew, Christopher A Brewster, Brooke L Walker, Logan C Spurdle, Amanda B Brown, Melissa A Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts |
title | Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts |
title_full | Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts |
title_fullStr | Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts |
title_full_unstemmed | Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts |
title_short | Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts |
title_sort | effect of brca2 sequence variants predicted to disrupt exonic splice enhancers on brca2 transcripts |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897790/ https://www.ncbi.nlm.nih.gov/pubmed/20507642 http://dx.doi.org/10.1186/1471-2350-11-80 |
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