A Comprehensive In Silico Analysis on the Structural and Functional Impact of SNPs in the Congenital Heart Defects Associated with NKX2-5 Gene-A Molecular Dynamic Simulation Approach.

Congenital heart defects (CHD) presented as structural defects in the heart and blood vessels during birth contribute an important cause of childhood morbidity and mortality worldwide. Many Single nucletotide polymorphisms (SNPs) in different genes have been associated with various types of congenit...

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Main Authors: Firoz Abdul Samad, Bandar A Suliman, Syed Hussain Basha, Thamilarasan Manivasagam, Musthafa Mohamed Essa
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4859487?pdf=render
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spelling doaj-4e45d5bcb26a4ddc8f317b4b3ca1a6e32020-11-25T00:04:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01115e015399910.1371/journal.pone.0153999A Comprehensive In Silico Analysis on the Structural and Functional Impact of SNPs in the Congenital Heart Defects Associated with NKX2-5 Gene-A Molecular Dynamic Simulation Approach.Firoz Abdul SamadBandar A SulimanSyed Hussain BashaThamilarasan ManivasagamMusthafa Mohamed EssaCongenital heart defects (CHD) presented as structural defects in the heart and blood vessels during birth contribute an important cause of childhood morbidity and mortality worldwide. Many Single nucletotide polymorphisms (SNPs) in different genes have been associated with various types of congenital heart defects. NKX 2-5 gene is one among them, which encodes a homeobox-containing transcription factor that plays a crucial role during the initial phases of heart formation and development. Mutations in this gene could cause different types of congenital heart defects, including Atrial septal defect (ASD), Atrial ventricular block (AVB), Tetralogy of fallot and ventricular septal defect. This highlights the importance of studying the impact of different SNPs found within this gene that might cause structural and functional modification of its encoded protein. In this study, we retrieved SNPs from the database (dbSNP), followed by identification of potentially deleterious Non-synonymous single nucleotide polymorphisms (nsSNPs) and prediction of their effect on proteins by computational screening using SIFT and Polyphen. Furthermore, we have carried out molecular dynamic simulation (MDS) in order to uncover the SNPs that would cause the most structural damage to the protein altering its biological function. The most important SNP that was found using our approach was rs137852685 R161P, which was predicted to cause the most damage to the structural features of the protein. Mapping nsSNPs in genes such as NKX 2-5 would provide valuable information about individuals carrying these polymorphisms, where such variations could be used as diagnostic markers.http://europepmc.org/articles/PMC4859487?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Firoz Abdul Samad
Bandar A Suliman
Syed Hussain Basha
Thamilarasan Manivasagam
Musthafa Mohamed Essa
spellingShingle Firoz Abdul Samad
Bandar A Suliman
Syed Hussain Basha
Thamilarasan Manivasagam
Musthafa Mohamed Essa
A Comprehensive In Silico Analysis on the Structural and Functional Impact of SNPs in the Congenital Heart Defects Associated with NKX2-5 Gene-A Molecular Dynamic Simulation Approach.
PLoS ONE
author_facet Firoz Abdul Samad
Bandar A Suliman
Syed Hussain Basha
Thamilarasan Manivasagam
Musthafa Mohamed Essa
author_sort Firoz Abdul Samad
title A Comprehensive In Silico Analysis on the Structural and Functional Impact of SNPs in the Congenital Heart Defects Associated with NKX2-5 Gene-A Molecular Dynamic Simulation Approach.
title_short A Comprehensive In Silico Analysis on the Structural and Functional Impact of SNPs in the Congenital Heart Defects Associated with NKX2-5 Gene-A Molecular Dynamic Simulation Approach.
title_full A Comprehensive In Silico Analysis on the Structural and Functional Impact of SNPs in the Congenital Heart Defects Associated with NKX2-5 Gene-A Molecular Dynamic Simulation Approach.
title_fullStr A Comprehensive In Silico Analysis on the Structural and Functional Impact of SNPs in the Congenital Heart Defects Associated with NKX2-5 Gene-A Molecular Dynamic Simulation Approach.
title_full_unstemmed A Comprehensive In Silico Analysis on the Structural and Functional Impact of SNPs in the Congenital Heart Defects Associated with NKX2-5 Gene-A Molecular Dynamic Simulation Approach.
title_sort comprehensive in silico analysis on the structural and functional impact of snps in the congenital heart defects associated with nkx2-5 gene-a molecular dynamic simulation approach.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2016-01-01
description Congenital heart defects (CHD) presented as structural defects in the heart and blood vessels during birth contribute an important cause of childhood morbidity and mortality worldwide. Many Single nucletotide polymorphisms (SNPs) in different genes have been associated with various types of congenital heart defects. NKX 2-5 gene is one among them, which encodes a homeobox-containing transcription factor that plays a crucial role during the initial phases of heart formation and development. Mutations in this gene could cause different types of congenital heart defects, including Atrial septal defect (ASD), Atrial ventricular block (AVB), Tetralogy of fallot and ventricular septal defect. This highlights the importance of studying the impact of different SNPs found within this gene that might cause structural and functional modification of its encoded protein. In this study, we retrieved SNPs from the database (dbSNP), followed by identification of potentially deleterious Non-synonymous single nucleotide polymorphisms (nsSNPs) and prediction of their effect on proteins by computational screening using SIFT and Polyphen. Furthermore, we have carried out molecular dynamic simulation (MDS) in order to uncover the SNPs that would cause the most structural damage to the protein altering its biological function. The most important SNP that was found using our approach was rs137852685 R161P, which was predicted to cause the most damage to the structural features of the protein. Mapping nsSNPs in genes such as NKX 2-5 would provide valuable information about individuals carrying these polymorphisms, where such variations could be used as diagnostic markers.
url http://europepmc.org/articles/PMC4859487?pdf=render
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