International Journal of Genetics and Genomics

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The Effect of Non-synonymous Single Nucleotide Polymorphisms Variants in ALPL Gene, a Computational Approach

Received: 6 July 2022    Accepted: 26 September 2022    Published: 29 December 2022
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Abstract

Background: Phosphorus is one of the major macronutrient essential for normal growth and development of living organisms. Alkaline phosphatase (ALP) is an enzyme present in human and animals responsible for solubilization and mineralization of organic phosphate and makes it readily available for the body. The disease Hypophosphatasia (HPP) is an autosomal recessive inherited one, branded by malfunctioning mineralization of bone, dental problems, and low serum ALP levels. This study aimed to scrutinize the effect of non-synonymous SNPs (nsSNPs) of ALPL gene on protein function and structure using different computational software. Material and Methods: Different Non-Synonymous Single Nucleotide Polymorphisms (nsSNPs) and protein related sequences were attained from NCBI and ExPASY databases. Deleterious and damaging effect of nsSNPs were analyzed using SIFT, Polyphen-2, Provean and SNPs&GO software. Protein stability was inspected using I-Mutant and MUpro software. The interaction of ALPL with other genes was studied using GeneMANIA software. The structural and functional influence of point mutations was predicted using Project Hope software. Results: ALPL gene was found to have an association with 20 other genes such as TRAF3 and TPP1 using GeneMANIA. It comprises a total of 485 SNPs out of that 188 were found to be synonymous, 298 were nsSNPs. Analysis of the nsSNPs by SIFT predicts 33 as deleterious and 265 as tolerated ones. Using Provean software, 26 were deleterious while 7 nsSNPs were neutral. Taking the deleterious nsSNPSs to Polyphen-2, 24 nsSNPs were damaging, while 2 were benign. Using SNPs&GO 13 nsSNPs were predicted as disease-related while 11 were predicted to be neutral. By using PHD SNPs 11 nsSNPs were predicted as disease-related while 13 were predicted to be neutral. Project Hope analyzes the mutations according to their size, charge, hydrophobicity, and conservancy. Conclusion: This study reveals 11 nsSNPs as being possibly pathogenic variants. Seven of them were already reported from previous studies by DNA sequencing, while the remaining four were predicted in this study for the first time.

DOI 10.11648/j.ijgg.20221004.12
Published in International Journal of Genetics and Genomics (Volume 10, Issue 4, December 2022)
Page(s) 94-102
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), 2024. Published by Science Publishing Group

Keywords

ALPL Gene, Computational Analysis, GeneMANIA, Hypophosphatasia, Non Synonymous SNP, SIFT, Polyphen-2

References
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Cite This Article
  • APA Style

    Nabaa Kamal Alshafei, Intisar Hassan Saeed, Mona Abdelrahman Mohamed Khaier. (2022). The Effect of Non-synonymous Single Nucleotide Polymorphisms Variants in ALPL Gene, a Computational Approach. International Journal of Genetics and Genomics, 10(4), 94-102. https://doi.org/10.11648/j.ijgg.20221004.12

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    ACS Style

    Nabaa Kamal Alshafei; Intisar Hassan Saeed; Mona Abdelrahman Mohamed Khaier. The Effect of Non-synonymous Single Nucleotide Polymorphisms Variants in ALPL Gene, a Computational Approach. Int. J. Genet. Genomics 2022, 10(4), 94-102. doi: 10.11648/j.ijgg.20221004.12

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    AMA Style

    Nabaa Kamal Alshafei, Intisar Hassan Saeed, Mona Abdelrahman Mohamed Khaier. The Effect of Non-synonymous Single Nucleotide Polymorphisms Variants in ALPL Gene, a Computational Approach. Int J Genet Genomics. 2022;10(4):94-102. doi: 10.11648/j.ijgg.20221004.12

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  • @article{10.11648/j.ijgg.20221004.12,
      author = {Nabaa Kamal Alshafei and Intisar Hassan Saeed and Mona Abdelrahman Mohamed Khaier},
      title = {The Effect of Non-synonymous Single Nucleotide Polymorphisms Variants in ALPL Gene, a Computational Approach},
      journal = {International Journal of Genetics and Genomics},
      volume = {10},
      number = {4},
      pages = {94-102},
      doi = {10.11648/j.ijgg.20221004.12},
      url = {https://doi.org/10.11648/j.ijgg.20221004.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20221004.12},
      abstract = {Background: Phosphorus is one of the major macronutrient essential for normal growth and development of living organisms. Alkaline phosphatase (ALP) is an enzyme present in human and animals responsible for solubilization and mineralization of organic phosphate and makes it readily available for the body. The disease Hypophosphatasia (HPP) is an autosomal recessive inherited one, branded by malfunctioning mineralization of bone, dental problems, and low serum ALP levels. This study aimed to scrutinize the effect of non-synonymous SNPs (nsSNPs) of ALPL gene on protein function and structure using different computational software. Material and Methods: Different Non-Synonymous Single Nucleotide Polymorphisms (nsSNPs) and protein related sequences were attained from NCBI and ExPASY databases. Deleterious and damaging effect of nsSNPs were analyzed using SIFT, Polyphen-2, Provean and SNPs&GO software. Protein stability was inspected using I-Mutant and MUpro software. The interaction of ALPL with other genes was studied using GeneMANIA software. The structural and functional influence of point mutations was predicted using Project Hope software. Results: ALPL gene was found to have an association with 20 other genes such as TRAF3 and TPP1 using GeneMANIA. It comprises a total of 485 SNPs out of that 188 were found to be synonymous, 298 were nsSNPs. Analysis of the nsSNPs by SIFT predicts 33 as deleterious and 265 as tolerated ones. Using Provean software, 26 were deleterious while 7 nsSNPs were neutral. Taking the deleterious nsSNPSs to Polyphen-2, 24 nsSNPs were damaging, while 2 were benign. Using SNPs&GO 13 nsSNPs were predicted as disease-related while 11 were predicted to be neutral. By using PHD SNPs 11 nsSNPs were predicted as disease-related while 13 were predicted to be neutral. Project Hope analyzes the mutations according to their size, charge, hydrophobicity, and conservancy. Conclusion: This study reveals 11 nsSNPs as being possibly pathogenic variants. Seven of them were already reported from previous studies by DNA sequencing, while the remaining four were predicted in this study for the first time.},
     year = {2022}
    }
    

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  • TY  - JOUR
    T1  - The Effect of Non-synonymous Single Nucleotide Polymorphisms Variants in ALPL Gene, a Computational Approach
    AU  - Nabaa Kamal Alshafei
    AU  - Intisar Hassan Saeed
    AU  - Mona Abdelrahman Mohamed Khaier
    Y1  - 2022/12/29
    PY  - 2022
    N1  - https://doi.org/10.11648/j.ijgg.20221004.12
    DO  - 10.11648/j.ijgg.20221004.12
    T2  - International Journal of Genetics and Genomics
    JF  - International Journal of Genetics and Genomics
    JO  - International Journal of Genetics and Genomics
    SP  - 94
    EP  - 102
    PB  - Science Publishing Group
    SN  - 2376-7359
    UR  - https://doi.org/10.11648/j.ijgg.20221004.12
    AB  - Background: Phosphorus is one of the major macronutrient essential for normal growth and development of living organisms. Alkaline phosphatase (ALP) is an enzyme present in human and animals responsible for solubilization and mineralization of organic phosphate and makes it readily available for the body. The disease Hypophosphatasia (HPP) is an autosomal recessive inherited one, branded by malfunctioning mineralization of bone, dental problems, and low serum ALP levels. This study aimed to scrutinize the effect of non-synonymous SNPs (nsSNPs) of ALPL gene on protein function and structure using different computational software. Material and Methods: Different Non-Synonymous Single Nucleotide Polymorphisms (nsSNPs) and protein related sequences were attained from NCBI and ExPASY databases. Deleterious and damaging effect of nsSNPs were analyzed using SIFT, Polyphen-2, Provean and SNPs&GO software. Protein stability was inspected using I-Mutant and MUpro software. The interaction of ALPL with other genes was studied using GeneMANIA software. The structural and functional influence of point mutations was predicted using Project Hope software. Results: ALPL gene was found to have an association with 20 other genes such as TRAF3 and TPP1 using GeneMANIA. It comprises a total of 485 SNPs out of that 188 were found to be synonymous, 298 were nsSNPs. Analysis of the nsSNPs by SIFT predicts 33 as deleterious and 265 as tolerated ones. Using Provean software, 26 were deleterious while 7 nsSNPs were neutral. Taking the deleterious nsSNPSs to Polyphen-2, 24 nsSNPs were damaging, while 2 were benign. Using SNPs&GO 13 nsSNPs were predicted as disease-related while 11 were predicted to be neutral. By using PHD SNPs 11 nsSNPs were predicted as disease-related while 13 were predicted to be neutral. Project Hope analyzes the mutations according to their size, charge, hydrophobicity, and conservancy. Conclusion: This study reveals 11 nsSNPs as being possibly pathogenic variants. Seven of them were already reported from previous studies by DNA sequencing, while the remaining four were predicted in this study for the first time.
    VL  - 10
    IS  - 4
    ER  - 

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Author Information
  • Department of Biochemistry, College of Veterinary Medicine, University of Bahri, Khartoum, Sudan

  • Department of Physiology, College of Veterinary Medicine, University of Bahri, Khartoum, Sudan

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

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