Estudos de SNPs no gene do receptor de serotonina 5HTR2A
Knowledge of the human genome has been rapidly expanded by innovative genome sequencing and bioinformatic analysis technologies, making it possible to detect variations in the genome: the variome. Substitutions of a single SNP (Single Nucleotide Polymorphism) nucleotide in DNA can have several alter...
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| Formato: | bachelorThesis |
| Idioma: | pt_BR |
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Universidade Federal do Rio Grande do Norte
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| Endereço do item: | https://repositorio.ufrn.br/handle/123456789/56843 |
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| Resumo: | Knowledge of the human genome has been rapidly expanded by innovative genome sequencing and bioinformatic analysis technologies, making it possible to detect variations in the genome: the variome. Substitutions of a single SNP (Single Nucleotide Polymorphism) nucleotide in DNA can have several alternative effects on the cell/individual. In the human body, neurotransmitters control several physiological processes, including serotonin. Changes in the 5HTR2A gene, which encodes the 5-hydroxytryptamine 2 A receptor, have been related to several neurological conditions that characterize a diagnosis of schizophrenia, obsessive-compulsive disorder, major depressive disorder (MDD), suicidal ideation, among others. This prospective study aims to evaluate genetic mutations (SNPs) in the 5HTR2A gene deposited in the dbSNP Short Genetic Variations database that can alter the amino acid composition of the protein. The SNP rs 1593423658 and SNP rs6308 were chosen and based on this information, three-dimensional normal and polymorphic 5HT2A protein models were obtained using 3D Homology Modeling on the SWISS MODEL online platform and also using AlphaFold2, a platform managed by Artificial Intelligence. Subsequently, Molecular Docking computational simulations were carried out to evaluate the interaction of the drugs Citalopram and Paroxetine. The polymorphic HTR2A proteins underwent changes in their 2D and 3D structure conformation when compared to the normal protein. Molecular Docking computational simulations revealed different interaction profiles for each ligand, consistent with the structural characteristics of each protein. Data from this preliminary prospective study suggest that genetic variations SNPs in the 5HTR2A gene may be important in the response to SSRI medications, as well as the interaction with serotonin, since these SNPs result in amino acid substitutions that alter the 3D structure of the 5HTR2A protein. |
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