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Prediction of Structural and Functional Effects of Single Nucleotide Polymorphisms in NAT2gene, a Computational Analysis

Received: 3 August 2019     Accepted: 4 October 2019     Published: 15 October 2019
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Abstract

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.

Published in International Journal of Genetics and Genomics (Volume 7, Issue 4)
DOI 10.11648/j.ijgg.20190704.11
Page(s) 88-97
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

NAT2gene, Computational Analysis, nsSNPs, 3ʹUTR

References
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  • APA Style

    Amna Elsadig Elsafi Abodlaa, Dalia Mursi, Mona Abdelrahman Mohamed Khaier, Mai Abdul RahmanMasri, Nazik Elmalaika Obaid Seid Ahmed Husain, et al. (2019). Prediction of Structural and Functional Effects of Single Nucleotide Polymorphisms in NAT2gene, a Computational Analysis. International Journal of Genetics and Genomics, 7(4), 88-97. https://doi.org/10.11648/j.ijgg.20190704.11

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    ACS Style

    Amna Elsadig Elsafi Abodlaa; Dalia Mursi; Mona Abdelrahman Mohamed Khaier; Mai Abdul RahmanMasri; Nazik Elmalaika Obaid Seid Ahmed Husain, et al. Prediction of Structural and Functional Effects of Single Nucleotide Polymorphisms in NAT2gene, a Computational Analysis. Int. J. Genet. Genomics 2019, 7(4), 88-97. doi: 10.11648/j.ijgg.20190704.11

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    AMA Style

    Amna Elsadig Elsafi Abodlaa, Dalia Mursi, Mona Abdelrahman Mohamed Khaier, Mai Abdul RahmanMasri, Nazik Elmalaika Obaid Seid Ahmed Husain, et al. Prediction of Structural and Functional Effects of Single Nucleotide Polymorphisms in NAT2gene, a Computational Analysis. Int J Genet Genomics. 2019;7(4):88-97. doi: 10.11648/j.ijgg.20190704.11

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  • @article{10.11648/j.ijgg.20190704.11,
      author = {Amna Elsadig Elsafi Abodlaa and Dalia Mursi and Mona Abdelrahman Mohamed Khaier and Mai Abdul RahmanMasri and Nazik Elmalaika Obaid Seid Ahmed Husain and Hind Abdelaziz Elnasri},
      title = {Prediction of Structural and Functional Effects of Single Nucleotide Polymorphisms in NAT2gene, a Computational Analysis},
      journal = {International Journal of Genetics and Genomics},
      volume = {7},
      number = {4},
      pages = {88-97},
      doi = {10.11648/j.ijgg.20190704.11},
      url = {https://doi.org/10.11648/j.ijgg.20190704.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20190704.11},
      abstract = {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.},
     year = {2019}
    }
    

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  • TY  - JOUR
    T1  - Prediction of Structural and Functional Effects of Single Nucleotide Polymorphisms in NAT2gene, a Computational Analysis
    AU  - Amna Elsadig Elsafi Abodlaa
    AU  - Dalia Mursi
    AU  - Mona Abdelrahman Mohamed Khaier
    AU  - Mai Abdul RahmanMasri
    AU  - Nazik Elmalaika Obaid Seid Ahmed Husain
    AU  - Hind Abdelaziz Elnasri
    Y1  - 2019/10/15
    PY  - 2019
    N1  - https://doi.org/10.11648/j.ijgg.20190704.11
    DO  - 10.11648/j.ijgg.20190704.11
    T2  - International Journal of Genetics and Genomics
    JF  - International Journal of Genetics and Genomics
    JO  - International Journal of Genetics and Genomics
    SP  - 88
    EP  - 97
    PB  - Science Publishing Group
    SN  - 2376-7359
    UR  - https://doi.org/10.11648/j.ijgg.20190704.11
    AB  - 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.
    VL  - 7
    IS  - 4
    ER  - 

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Author Information
  • Department of Molecular Biology and Bioinformatics, University of Bahri, Khartoum, Sudan

  • Central Laboratory, Ministry of Higher Education and Scientific Research, Sudan

  • Department of Molecular Biology and Bioinformatics, University of Bahri, Khartoum, Sudan

  • Department of Zoology, Molecular Biology, University of Khartoum, Khartoum, Sudan

  • Department of Pathology, Omdurman Islamic University, Omdurman, Sudan

  • Department of Molecular Biology and Bioinformatics, University of Bahri, Khartoum, Sudan

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