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A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene

Disease phenotypes and defects in function can be traced to nonsynonymous single nucleotide polymorphisms (nsSNPs), which are important indicators of action sites and effective potential therapeutic approaches. Identification of deleterious nsSNPs is crucial to characterize the genetic basis of dise...

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Autores principales: Marín-Martín, Francisco R., Soler-Rivas, Cristina, Martín-Hernández, Roberto, Rodriguez-Casado, Arantxa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156994/
https://www.ncbi.nlm.nih.gov/pubmed/25215231
http://dx.doi.org/10.1155/2014/639751
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author Marín-Martín, Francisco R.
Soler-Rivas, Cristina
Martín-Hernández, Roberto
Rodriguez-Casado, Arantxa
author_facet Marín-Martín, Francisco R.
Soler-Rivas, Cristina
Martín-Hernández, Roberto
Rodriguez-Casado, Arantxa
author_sort Marín-Martín, Francisco R.
collection PubMed
description Disease phenotypes and defects in function can be traced to nonsynonymous single nucleotide polymorphisms (nsSNPs), which are important indicators of action sites and effective potential therapeutic approaches. Identification of deleterious nsSNPs is crucial to characterize the genetic basis of diseases, assess individual susceptibility to disease, determinate molecular and therapeutic targets, and predict clinical phenotypes. In this study using PolyPhen2 and MutPred in silico algorithms, we analyzed the genetic variations that can alter the expression and function of the ABCA1 gene that causes the allelic disorders familial hypoalphalipoproteinemia and Tangier disease. Predictions were validated with published results from in vitro, in vivo, and human studies. Out of a total of 233 nsSNPs, 80 (34.33%) were found deleterious by both methods. Among these 80 deleterious nsSNPs found, 29 (12.44%) rare variants resulted highly deleterious with a probability >0.8. We have observed that mostly variants with verified functional effect in experimental studies are correctly predicted as damage variants by MutPred and PolyPhen2 tools. Still, the controversial results of experimental approaches correspond to nsSNPs predicted as neutral by both methods, or contradictory predictions are obtained for them. A total of seventeen nsSNPs were predicted as deleterious by PolyPhen2, which resulted neutral by MutPred. Otherwise, forty two nsSNPs were predicted as deleterious by MutPred, which resulted neutral by PolyPhen2.
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spelling pubmed-41569942014-09-11 A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene Marín-Martín, Francisco R. Soler-Rivas, Cristina Martín-Hernández, Roberto Rodriguez-Casado, Arantxa Cholesterol Research Article Disease phenotypes and defects in function can be traced to nonsynonymous single nucleotide polymorphisms (nsSNPs), which are important indicators of action sites and effective potential therapeutic approaches. Identification of deleterious nsSNPs is crucial to characterize the genetic basis of diseases, assess individual susceptibility to disease, determinate molecular and therapeutic targets, and predict clinical phenotypes. In this study using PolyPhen2 and MutPred in silico algorithms, we analyzed the genetic variations that can alter the expression and function of the ABCA1 gene that causes the allelic disorders familial hypoalphalipoproteinemia and Tangier disease. Predictions were validated with published results from in vitro, in vivo, and human studies. Out of a total of 233 nsSNPs, 80 (34.33%) were found deleterious by both methods. Among these 80 deleterious nsSNPs found, 29 (12.44%) rare variants resulted highly deleterious with a probability >0.8. We have observed that mostly variants with verified functional effect in experimental studies are correctly predicted as damage variants by MutPred and PolyPhen2 tools. Still, the controversial results of experimental approaches correspond to nsSNPs predicted as neutral by both methods, or contradictory predictions are obtained for them. A total of seventeen nsSNPs were predicted as deleterious by PolyPhen2, which resulted neutral by MutPred. Otherwise, forty two nsSNPs were predicted as deleterious by MutPred, which resulted neutral by PolyPhen2. Hindawi Publishing Corporation 2014 2014-08-19 /pmc/articles/PMC4156994/ /pubmed/25215231 http://dx.doi.org/10.1155/2014/639751 Text en Copyright © 2014 Francisco R. Marín-Martín et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Marín-Martín, Francisco R.
Soler-Rivas, Cristina
Martín-Hernández, Roberto
Rodriguez-Casado, Arantxa
A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene
title A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene
title_full A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene
title_fullStr A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene
title_full_unstemmed A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene
title_short A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene
title_sort comprehensive in silico analysis of the functional and structural impact of nonsynonymous snps in the abca1 transporter gene
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156994/
https://www.ncbi.nlm.nih.gov/pubmed/25215231
http://dx.doi.org/10.1155/2014/639751
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