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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Serotonina Serotonin Polimorfismos Polymorphisms Neuropatologias Neuropathologies |
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Serotonina Serotonin Polimorfismos Polymorphisms Neuropatologias Neuropathologies Silva, Fabiana Lúcio da Estudos de SNPs no gene do receptor de serotonina 5HTR2A |
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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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Blaha, Carlos Alfredo Galindo |
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Blaha, Carlos Alfredo Galindo Silva, Fabiana Lúcio da |
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bachelorThesis |
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Silva, Fabiana Lúcio da |
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Silva, Fabiana Lúcio da |
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Estudos de SNPs no gene do receptor de serotonina 5HTR2A |
title_short |
Estudos de SNPs no gene do receptor de serotonina 5HTR2A |
title_full |
Estudos de SNPs no gene do receptor de serotonina 5HTR2A |
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Estudos de SNPs no gene do receptor de serotonina 5HTR2A |
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Estudos de SNPs no gene do receptor de serotonina 5HTR2A |
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estudos de snps no gene do receptor de serotonina 5htr2a |
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Universidade Federal do Rio Grande do Norte |
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2023 |
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https://repositorio.ufrn.br/handle/123456789/56843 |
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AT silvafabianalucioda estudosdesnpsnogenedoreceptordeserotonina5htr2a AT silvafabianalucioda studiesofsnpsinthe5htr2aserotoninreceptorgene |
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ri-123456789-568432023-12-22T17:03:12Z Estudos de SNPs no gene do receptor de serotonina 5HTR2A Studies of SNPs in the 5HTR2A serotonin receptor gene Silva, Fabiana Lúcio da Blaha, Carlos Alfredo Galindo http://lattes.cnpq.br/2307806644081146 Lúcio, Paulo Sérgio Marinho http://lattes.cnpq.br/8301201882084757 Gavioli, Elaine Cristina http://lattes.cnpq.br/1759328747578795 Serotonina Serotonin Polimorfismos Polymorphisms Neuropatologias Neuropathologies 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. O conhecimento do genoma humano tem sido rapidamente expandido pelas inovadoras tecnologias de seqüenciamento de genomas e analise bioinformática sendo possível hoje detectar variações no genoma: o variome. As substituições de um único nucleotídeo SNP (Single nucleotide polimorphism) no DNA podem ter diversas alternativas de efeitos na célula/individuo. No corpo humano os neurotransmissores controlam diversos processos fisiológicos, dentre eles a serotonina. Alterações no gene 5HTR2A, que codifica o receptor de 5-hidroxitriptamina2A, tem sido relacionado com várias condições neurológicas que caracteriza um diagnóstico de esquizofrenia, transtorno obsessivo-compulsivo, transtorno depressivo maior (TDM), ideação suicida dentre outros. Este estudo prospectivo tem como objetivo avaliar mutações genéticas (SNPs) no gene 5HTR2A depositadas o banco de dados dbSNP Short GeneticVariationsque podem em alterar a composição de aminoácidos da proteína. Foram escolhidas os SNP rs 1593423658 e SNP rs6308 e a partir destas informações,modelos tridimensionais proteína 5HT2A normal e polimórfica foram obtidos utilizando a Modelagem 3D por Homologia na plataforma online SWISS MODEL e também utilizando AlphaFold2, uma plataforma gerenciada por Inteligência Artificial. Posteriormente, foram realizadas simulações computacionais de Docking Molecular para avaliar a interação dos medicamentos Citalopram e Paroxetina. As proteínas 5HTR2A polimórficas apresentaram mudanças em sua conformação de estrutura 2D e 3D quando comparadas com a proteína normal. As simulações computacionais de Docking Molecular revelaram diferentes perfis de interação para cada ligante, consistentes com as características estruturais de cada proteína. Os dados deste estudo prospectivo preliminar sugerem que, as variações genéticas de SNPs no gene 5HTR2A, podem ter importância na resposta a fármacos ISRS, bem como a interação com à serotonina, uma vez estes SNPs resultam em substituições de aminoácidos que alteram a estrutura 3D da proteína 5HTR2A. Palavras-chave: Serotonina; polimorfismos; Neuropatologias; ISRSs. 2023-12-22T17:03:11Z 2023-12-22T17:03:11Z 2023-12-18 bachelorThesis SILVA, Fabiana Lúcio. Estudos de SNPs no receptor de serotonina 5HTR2A. 2023. 68f. Trabalho de Conclusão de Curso (Graduação em Biomedicina). Centro de Biociências. Universidade Federal do Rio Grande do Norte. Natal, 2023. https://repositorio.ufrn.br/handle/123456789/56843 pt_BR Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ application/pdf Universidade Federal do Rio Grande do Norte Brasil UFRN BIOMEDICINA DEPARTAMENTO DE BIOLOGIA CELULAR E GENETICA |