In silico profiling of non-synonymous SNPs in IDS gene for early diagnosis of Hunter syndrome
Abstract Background Single amino acid substitutions in the Iduronate-2-sulfatase enzyme result in destabilization of the protein and cause a genetic disorder called Hunter syndrome. To gain functional insight into the mutations causing Hunter syndrome, various bioinformatics tools were employed, and...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2022-03-01
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| Series: | Egyptian Journal of Medical Human Genetics |
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| Online Access: | https://doi.org/10.1186/s43042-022-00271-3 |
| _version_ | 1818245660775809024 |
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| author | Adarshan Sivakumar Yuvaraj Dinakarkumar Wahidah H. Al-Qahtani Muthusamy Karnan Jothiramalingam Rajabathar Arokiyaraj Charumathi Elakiya Sadhaasivam Aparna Preetha Venugopal Baljeet Mukhtiar Singh Maqbool Qutub Sai Ramesh Anjaneyulu |
| author_facet | Adarshan Sivakumar Yuvaraj Dinakarkumar Wahidah H. Al-Qahtani Muthusamy Karnan Jothiramalingam Rajabathar Arokiyaraj Charumathi Elakiya Sadhaasivam Aparna Preetha Venugopal Baljeet Mukhtiar Singh Maqbool Qutub Sai Ramesh Anjaneyulu |
| author_sort | Adarshan Sivakumar |
| collection | DOAJ |
| description | Abstract Background Single amino acid substitutions in the Iduronate-2-sulfatase enzyme result in destabilization of the protein and cause a genetic disorder called Hunter syndrome. To gain functional insight into the mutations causing Hunter syndrome, various bioinformatics tools were employed, and special significance is given to molecular docking. Results In-silico tools available online for preliminary analysis including SIFT, PolyPhen 2.0, etc., were primarily employed and have identified 51 Non-synonymous Single Nucleotide Polymorphisms (ns-SNPs) as possibly deleterious. Further, modelling and energy minimization followed by Root Mean Square Deviation (RMSD) calculation has labelled 42 mutations as probably deleterious ns-SNPs. Later, trajectory analysis was performed using online tools like PSIPRED, SRide, etc., and has predicted six ns-SNPs as potentially deleterious. Additionally, docking was performed, and three candidate ns-SNPs were identified. Finally, these three ns-SNPs were confirmed to play a significant role in causing syndrome through root mean square fluctuation (RMSF) calculations. Conclusion From the observed results, G134E, V503D, and E521D were predicted to be candidate ns-SNPs in comparison with other in-silico tools and confirmed by RMSF calculations. Thus, the identified candidate ns-SNPs can be employed as a potential genetic marker in the early diagnosis of Hunter syndrome after clinical validation. |
| first_indexed | 2024-12-12T14:36:27Z |
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| id | doaj.art-f84260d89df1430bb64854025c88a002 |
| institution | Directory Open Access Journal |
| issn | 2090-2441 |
| language | English |
| last_indexed | 2024-12-12T14:36:27Z |
| publishDate | 2022-03-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj.art-f84260d89df1430bb64854025c88a0022022-12-22T00:21:23ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412022-03-012311910.1186/s43042-022-00271-3In silico profiling of non-synonymous SNPs in IDS gene for early diagnosis of Hunter syndromeAdarshan Sivakumar0Yuvaraj Dinakarkumar1Wahidah H. Al-Qahtani2Muthusamy Karnan3Jothiramalingam Rajabathar4Arokiyaraj Charumathi5Elakiya Sadhaasivam6Aparna Preetha Venugopal7Baljeet Mukhtiar Singh8Maqbool Qutub9Sai Ramesh Anjaneyulu10Department of Biotechnology, Alagappa UniversityDepartment of Biotechnology, Vel Tech High-Tech Dr. Rangarajan Dr. Sakunthala Engineering CollegeDepartment of Food Sciences and Nutrition, College of Food and Agriculture Sciences, King Saud UniversityGrassland and Forage Division, National Institute of Animal Science, Rural Development AdministrationDepartment of Food Sciences and Nutrition, College of Food and Agriculture Sciences, King Saud UniversityDepartment of Biotechnology, Sree Sastha Institute of Engineering and Technology (Anna University)Department of Biotechnology, Kongunadu Arts and Science CollegeDepartment of Advanced Biochemistry, University of MadrasDepartment of Zoology, Punjabi UniversityDepartment of Agricultural Biotechnology, Tamil Nadu Agricultural UniversityDepartment of Biotechnology, Vel Tech High-Tech Dr. Rangarajan Dr. Sakunthala Engineering CollegeAbstract Background Single amino acid substitutions in the Iduronate-2-sulfatase enzyme result in destabilization of the protein and cause a genetic disorder called Hunter syndrome. To gain functional insight into the mutations causing Hunter syndrome, various bioinformatics tools were employed, and special significance is given to molecular docking. Results In-silico tools available online for preliminary analysis including SIFT, PolyPhen 2.0, etc., were primarily employed and have identified 51 Non-synonymous Single Nucleotide Polymorphisms (ns-SNPs) as possibly deleterious. Further, modelling and energy minimization followed by Root Mean Square Deviation (RMSD) calculation has labelled 42 mutations as probably deleterious ns-SNPs. Later, trajectory analysis was performed using online tools like PSIPRED, SRide, etc., and has predicted six ns-SNPs as potentially deleterious. Additionally, docking was performed, and three candidate ns-SNPs were identified. Finally, these three ns-SNPs were confirmed to play a significant role in causing syndrome through root mean square fluctuation (RMSF) calculations. Conclusion From the observed results, G134E, V503D, and E521D were predicted to be candidate ns-SNPs in comparison with other in-silico tools and confirmed by RMSF calculations. Thus, the identified candidate ns-SNPs can be employed as a potential genetic marker in the early diagnosis of Hunter syndrome after clinical validation.https://doi.org/10.1186/s43042-022-00271-3IDS geneHunter syndromeMolecular dockingTrajectory analysisRMSFNs-SNPs |
| spellingShingle | Adarshan Sivakumar Yuvaraj Dinakarkumar Wahidah H. Al-Qahtani Muthusamy Karnan Jothiramalingam Rajabathar Arokiyaraj Charumathi Elakiya Sadhaasivam Aparna Preetha Venugopal Baljeet Mukhtiar Singh Maqbool Qutub Sai Ramesh Anjaneyulu In silico profiling of non-synonymous SNPs in IDS gene for early diagnosis of Hunter syndrome Egyptian Journal of Medical Human Genetics IDS gene Hunter syndrome Molecular docking Trajectory analysis RMSF Ns-SNPs |
| title | In silico profiling of non-synonymous SNPs in IDS gene for early diagnosis of Hunter syndrome |
| title_full | In silico profiling of non-synonymous SNPs in IDS gene for early diagnosis of Hunter syndrome |
| title_fullStr | In silico profiling of non-synonymous SNPs in IDS gene for early diagnosis of Hunter syndrome |
| title_full_unstemmed | In silico profiling of non-synonymous SNPs in IDS gene for early diagnosis of Hunter syndrome |
| title_short | In silico profiling of non-synonymous SNPs in IDS gene for early diagnosis of Hunter syndrome |
| title_sort | in silico profiling of non synonymous snps in ids gene for early diagnosis of hunter syndrome |
| topic | IDS gene Hunter syndrome Molecular docking Trajectory analysis RMSF Ns-SNPs |
| url | https://doi.org/10.1186/s43042-022-00271-3 |
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