Bioinformatic Characterization of the Functional and Structural Effect of Single Nucleotide Mutations in Patients with High-Grade Glioma
<b>Background:</b> Gliomas are neoplasms of the central nervous system that originate in glial cells. The genetic characteristics of this type of neoplasm are the loss of function of tumor suppressor genes such as <i>TP53</i> and somatic mutations in genes such as <i>ID...
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2024-10-01
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| author | Sara Vélez Gómez Juliana María Martínez Garro León Darío Ortiz Gómez Jorge Emilio Salazar Flórez Fernando P. Monroy Ronald Guillermo Peláez Sánchez |
| author_facet | Sara Vélez Gómez Juliana María Martínez Garro León Darío Ortiz Gómez Jorge Emilio Salazar Flórez Fernando P. Monroy Ronald Guillermo Peláez Sánchez |
| author_sort | Sara Vélez Gómez |
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| description | <b>Background:</b> Gliomas are neoplasms of the central nervous system that originate in glial cells. The genetic characteristics of this type of neoplasm are the loss of function of tumor suppressor genes such as <i>TP53</i> and somatic mutations in genes such as <i>IDH1/2</i>. Additionally, in clinical cases, de novo single nucleotide polymorphisms (SNP) are reported, of which their pathogenicity and their effects on the function and stability of the protein are known. <b>Methodology:</b> Non-synonymous SNPs were analyzed for their structural and functional effect on proteins using a set of bioinformatics tools such as SIFT, PolyPhen-2, PhD-SNP, I-Mutant 3.0, MUpro, and mutation3D. A structural comparison between normal and mutated residues for disease-associated coding SNPs was performed using TM-aling and the SWISS MODEL. <b>Results:</b> A total of 13 SNPs were obtained for the <i>TP53</i> gene, 1 SNP for <i>IDH1</i>, and 1 for <i>IDH2</i>, which would be functionally detrimental and associated with disease. Additionally, these changes compromise the structure and function of the protein; the A161S SNP for <i>TP53</i> that has not been reported in any databases was classified as detrimental. <b>Conclusions:</b> All non-synonymous SNPs reported for <i>TP53</i> were in the region of the deoxyribonucleic acid (DNA) binding domain and had a great impact on the function and stability of the protein. In addition, the two polymorphisms detected in <i>IDH1</i> and <i>IDH2</i> genes compromise the structure and activity of the protein. Both genes are related to the development of high-grade gliomas. All the data obtained in this study must be validated through experimental approaches. |
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| language | English |
| publishDate | 2024-10-01 |
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| spelling | doaj-art-8e231d12727246729cbf5e2f228f14c72025-08-20T02:11:01ZengMDPI AGBiomedicines2227-90592024-10-011210228710.3390/biomedicines12102287Bioinformatic Characterization of the Functional and Structural Effect of Single Nucleotide Mutations in Patients with High-Grade GliomaSara Vélez Gómez0Juliana María Martínez Garro1León Darío Ortiz Gómez2Jorge Emilio Salazar Flórez3Fernando P. Monroy4Ronald Guillermo Peláez Sánchez5Faculty of Sciences and Biotechnology, CES University, Medellín 050021, ColombiaCES Biology, Science and Biotechnology School, CES University, Medellín 050021, ColombiaCancer Institute, Las Americas-AUNA Clinic, Medellín 050023, ColombiaGEINCRO Research Group, Medicine Program, School of Health Sciences, San Martín University Foundation, Sabaneta 055457, ColombiaDepartment of Biological Sciences, Northerm Arizona University, Flagstaff, AZ 85721, USALife and Health Sciences Research Group, Graduate School, CES University, Medellín 050021, Colombia<b>Background:</b> Gliomas are neoplasms of the central nervous system that originate in glial cells. The genetic characteristics of this type of neoplasm are the loss of function of tumor suppressor genes such as <i>TP53</i> and somatic mutations in genes such as <i>IDH1/2</i>. Additionally, in clinical cases, de novo single nucleotide polymorphisms (SNP) are reported, of which their pathogenicity and their effects on the function and stability of the protein are known. <b>Methodology:</b> Non-synonymous SNPs were analyzed for their structural and functional effect on proteins using a set of bioinformatics tools such as SIFT, PolyPhen-2, PhD-SNP, I-Mutant 3.0, MUpro, and mutation3D. A structural comparison between normal and mutated residues for disease-associated coding SNPs was performed using TM-aling and the SWISS MODEL. <b>Results:</b> A total of 13 SNPs were obtained for the <i>TP53</i> gene, 1 SNP for <i>IDH1</i>, and 1 for <i>IDH2</i>, which would be functionally detrimental and associated with disease. Additionally, these changes compromise the structure and function of the protein; the A161S SNP for <i>TP53</i> that has not been reported in any databases was classified as detrimental. <b>Conclusions:</b> All non-synonymous SNPs reported for <i>TP53</i> were in the region of the deoxyribonucleic acid (DNA) binding domain and had a great impact on the function and stability of the protein. In addition, the two polymorphisms detected in <i>IDH1</i> and <i>IDH2</i> genes compromise the structure and activity of the protein. Both genes are related to the development of high-grade gliomas. All the data obtained in this study must be validated through experimental approaches.https://www.mdpi.com/2227-9059/12/10/2287neoplasia of the central nervous systemcomputational analysisproteinvariant<i>TP53</i><i>IDH1</i> |
| spellingShingle | Sara Vélez Gómez Juliana María Martínez Garro León Darío Ortiz Gómez Jorge Emilio Salazar Flórez Fernando P. Monroy Ronald Guillermo Peláez Sánchez Bioinformatic Characterization of the Functional and Structural Effect of Single Nucleotide Mutations in Patients with High-Grade Glioma Biomedicines neoplasia of the central nervous system computational analysis protein variant <i>TP53</i> <i>IDH1</i> |
| title | Bioinformatic Characterization of the Functional and Structural Effect of Single Nucleotide Mutations in Patients with High-Grade Glioma |
| title_full | Bioinformatic Characterization of the Functional and Structural Effect of Single Nucleotide Mutations in Patients with High-Grade Glioma |
| title_fullStr | Bioinformatic Characterization of the Functional and Structural Effect of Single Nucleotide Mutations in Patients with High-Grade Glioma |
| title_full_unstemmed | Bioinformatic Characterization of the Functional and Structural Effect of Single Nucleotide Mutations in Patients with High-Grade Glioma |
| title_short | Bioinformatic Characterization of the Functional and Structural Effect of Single Nucleotide Mutations in Patients with High-Grade Glioma |
| title_sort | bioinformatic characterization of the functional and structural effect of single nucleotide mutations in patients with high grade glioma |
| topic | neoplasia of the central nervous system computational analysis protein variant <i>TP53</i> <i>IDH1</i> |
| url | https://www.mdpi.com/2227-9059/12/10/2287 |
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