Computational Prediction of the Effects of Single Nucleotide Polymorphisms of the Gene Encoding Human Endothelial Nitric Oxide Synthase
ABSTRACT Background and Objective: Genetic variations in the gene encoding endothelial nitric oxide synthase (eNOS) enzyme affect the susceptibility to cardiovascular disease. Identification of the way these changes affect eNOS structure and function in laboratory conditions is difficult...
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| Format: | Article |
| Language: | English |
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Golestan University of Medical Sciences
2016-05-01
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| Series: | Medical Laboratory Journal |
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| Online Access: | http://mlj.goums.ac.ir/article-1-856-en.html |
| _version_ | 1828851966401314816 |
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| author | Esmaeil Samadian Ayyoob Khosravi Roghaye Gharae Mostafa Mir Seyed Ahmad Sajjadi Fahimeh Mohammad Abadi Nader Hashemi Sahar Alijanpour Hamid Reza Joshaghani |
| author_facet | Esmaeil Samadian Ayyoob Khosravi Roghaye Gharae Mostafa Mir Seyed Ahmad Sajjadi Fahimeh Mohammad Abadi Nader Hashemi Sahar Alijanpour Hamid Reza Joshaghani |
| author_sort | Esmaeil Samadian |
| collection | DOAJ |
| description | ABSTRACT
Background and Objective: Genetic variations in the gene encoding endothelial nitric oxide synthase (eNOS) enzyme affect the susceptibility to cardiovascular disease. Identification of the way these changes affect eNOS structure and function in laboratory conditions is difficult and time-consuming. Thus, it seems essential to perform bioinformatics studies prior to laboratory studies to find the variants that are more important. This study aimed to predict the damaging effect of changes in the coding region of eNOS using homology- and structure-based algorithms (SIFT and PolyPhen).
Methods: First, the single nucleotide polymorphisms in the coding region (cSNPs) of the human eNOS gene were extracted from dbSNP. Resulting amino acid changes were reported as primary data required for the study. Then, position and type of amino acid changes along with the complete amino acid sequence were separately entered into the SIFT and PolyPhen tools for analysis.
Results: Of 144 single nucleotide changes, 38 changes by the SIFT, 47 changes by the PolyPhen and 18 amino acid substitutions by both tools were predicted as damaging.
Conclusion: It is predicted that 18 amino acid changes may have damaging phenotypic effects on the structure of the eNOS enzyme that may affect its performance by potentially affecting the enzyme’s various functional regions. Therefore, computational prediction of potentially damaging nsSNPs and prioritizing amino acid changes may be useful for investigating protein performance using targeted re-sequencing and gene mutagenesis experiments. |
| first_indexed | 2024-12-12T23:43:02Z |
| format | Article |
| id | doaj.art-b2d71f4651d546e5bc03ed3afb9dc2ff |
| institution | Directory Open Access Journal |
| issn | 2538-4449 |
| language | English |
| last_indexed | 2024-12-12T23:43:02Z |
| publishDate | 2016-05-01 |
| publisher | Golestan University of Medical Sciences |
| record_format | Article |
| series | Medical Laboratory Journal |
| spelling | doaj.art-b2d71f4651d546e5bc03ed3afb9dc2ff2022-12-22T00:07:03ZengGolestan University of Medical SciencesMedical Laboratory Journal2538-44492016-05-0110315Computational Prediction of the Effects of Single Nucleotide Polymorphisms of the Gene Encoding Human Endothelial Nitric Oxide SynthaseEsmaeil Samadian0Ayyoob Khosravi1Roghaye Gharae2Mostafa Mir3Seyed Ahmad Sajjadi4Fahimeh Mohammad Abadi5Nader Hashemi6Sahar Alijanpour7Hamid Reza Joshaghani8 Department of Molecular Medicine Department of Molecular Medicine Laboratory Sciences Research Center Department of Clinical Biochemistry Reference Laboratory Department of Clinical Biochemistry Department of Clinical Biochemistry department of medical genetics, Faculty of advanced medical technologies, Golestan university of medical sciences, Gorgan, Iran Laboratory Sciences Research Center, Golestan University of Medical Science, Gorgan, Iran ABSTRACT Background and Objective: Genetic variations in the gene encoding endothelial nitric oxide synthase (eNOS) enzyme affect the susceptibility to cardiovascular disease. Identification of the way these changes affect eNOS structure and function in laboratory conditions is difficult and time-consuming. Thus, it seems essential to perform bioinformatics studies prior to laboratory studies to find the variants that are more important. This study aimed to predict the damaging effect of changes in the coding region of eNOS using homology- and structure-based algorithms (SIFT and PolyPhen). Methods: First, the single nucleotide polymorphisms in the coding region (cSNPs) of the human eNOS gene were extracted from dbSNP. Resulting amino acid changes were reported as primary data required for the study. Then, position and type of amino acid changes along with the complete amino acid sequence were separately entered into the SIFT and PolyPhen tools for analysis. Results: Of 144 single nucleotide changes, 38 changes by the SIFT, 47 changes by the PolyPhen and 18 amino acid substitutions by both tools were predicted as damaging. Conclusion: It is predicted that 18 amino acid changes may have damaging phenotypic effects on the structure of the eNOS enzyme that may affect its performance by potentially affecting the enzyme’s various functional regions. Therefore, computational prediction of potentially damaging nsSNPs and prioritizing amino acid changes may be useful for investigating protein performance using targeted re-sequencing and gene mutagenesis experiments.http://mlj.goums.ac.ir/article-1-856-en.htmlenosnon-synonymous snpfunctional impacts. |
| spellingShingle | Esmaeil Samadian Ayyoob Khosravi Roghaye Gharae Mostafa Mir Seyed Ahmad Sajjadi Fahimeh Mohammad Abadi Nader Hashemi Sahar Alijanpour Hamid Reza Joshaghani Computational Prediction of the Effects of Single Nucleotide Polymorphisms of the Gene Encoding Human Endothelial Nitric Oxide Synthase Medical Laboratory Journal enos non-synonymous snp functional impacts. |
| title | Computational Prediction of the Effects of Single Nucleotide Polymorphisms of the Gene Encoding Human Endothelial Nitric Oxide Synthase |
| title_full | Computational Prediction of the Effects of Single Nucleotide Polymorphisms of the Gene Encoding Human Endothelial Nitric Oxide Synthase |
| title_fullStr | Computational Prediction of the Effects of Single Nucleotide Polymorphisms of the Gene Encoding Human Endothelial Nitric Oxide Synthase |
| title_full_unstemmed | Computational Prediction of the Effects of Single Nucleotide Polymorphisms of the Gene Encoding Human Endothelial Nitric Oxide Synthase |
| title_short | Computational Prediction of the Effects of Single Nucleotide Polymorphisms of the Gene Encoding Human Endothelial Nitric Oxide Synthase |
| title_sort | computational prediction of the effects of single nucleotide polymorphisms of the gene encoding human endothelial nitric oxide synthase |
| topic | enos non-synonymous snp functional impacts. |
| url | http://mlj.goums.ac.ir/article-1-856-en.html |
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