Volume 7, Issue 4, December 2019, Page: 88-97
Prediction of Structural and Functional Effects of Single Nucleotide Polymorphisms in NAT2gene, a Computational Analysis
Amna Elsadig Elsafi Abodlaa, Department of Molecular Biology and Bioinformatics, University of Bahri, Khartoum, Sudan; Haematology Department, Research and Laboratory Unit, Khartoum Teaching Hospital, Sudan; College of Medical Laboratory, Sudan University of Science and Technology, Sudan
Dalia Mursi, Central Laboratory, Ministry of Higher Education and Scientific Research, Sudan
Mona Abdelrahman Mohamed Khaier, Department of Molecular Biology and Bioinformatics, University of Bahri, Khartoum, Sudan
Mai Abdul RahmanMasri, Department of Zoology, Molecular Biology, University of Khartoum, Khartoum, Sudan
Nazik Elmalaika Obaid Seid Ahmed Husain, Department of Pathology, Omdurman Islamic University, Omdurman, Sudan
Hind Abdelaziz Elnasri, Department of Molecular Biology and Bioinformatics, University of Bahri, Khartoum, Sudan
Received: Aug. 3, 2019;       Accepted: Oct. 4, 2019;       Published: Oct. 15, 2019
DOI: 10.11648/j.ijgg.20190704.11      View  125      Downloads  49
N-acetyltransferase 2 (encoded by NAT2) is a phase II enzyme that detoxifies and metabolizes xenobiotics and drugs components. It is a critical enzyme in clinical pharmacology. It has remarkable genetic polymorphisms, which is associated with the risk of developing cancer due to the change of normally fast acetylation of substrates to slow acetylation. This study assessed single nucleotide polymorphisms (SNPs) in the coding region and (3ʹUTR) of NAT2. Computational approaches were used in this study for functional and structural effects of NAT2 gene. SNPs. Were retrieved from NCBI SNPsdatabase. TheNAT2 protein sequence and amino acid change were used as an input to the SIFT, PolyPhen-2, PhD-SNP, SNPs& GO, SNPAnalyzer, I-Mutant 3.0 and PMut to determine the deleterious and SNPs conditions. Other software for predication of the structural change were Mutation3D, Chimera and Project HOPE. GeneMANIA software was used to show gene –gene interaction. PolymiRTs was used to investigate the disruption or creation of SNPs of miRNA region. In Homosapiens182 were nonsynonymous SNPs (nsSNPs), 60 synonymous SNPs, 48 3ʹUTRSNPs and 19 5ʹUTR SNPs. A total, 65 of thosensSNPs were predicted to be highly damaging with 3-6 score rates when analyzed with six software. Re-computation of results with I-Mutant 3.0 showed adecrease in the effective stability of the protein due to 55 nsSNPs. Consequent structural changes were shown using Project HOPE and Chimera. NAT2 is a highly polymorphic gene; the majority of deleterious NAT2SNPs are nsSNPs that alter the physiochemical and structural properties of the protein, possibly leading to the loss or distortion of the protein's ability to detoxify and metabolize xenobiotic and aromatic amine compounds. There were three SNPs at the 3ʹUTR that changed the miRNA binding sites, which might affect the gene regulation.
NAT2gene, Computational Analysis, nsSNPs, 3ʹUTR
To cite this article
Amna Elsadig Elsafi Abodlaa, Dalia Mursi, Mona Abdelrahman Mohamed Khaier, Mai Abdul RahmanMasri, Nazik Elmalaika Obaid Seid Ahmed Husain, Hind Abdelaziz Elnasri, Prediction of Structural and Functional Effects of Single Nucleotide Polymorphisms in NAT2gene, a Computational Analysis, International Journal of Genetics and Genomics. Vol. 7, No. 4, 2019, pp. 88-97. doi: 10.11648/j.ijgg.20190704.11
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This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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