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Authors
Advisor(s)
Abstract(s)
A sequência genómica esteve, durante muitos anos, apenas associada à sua capacidade de codificar proteínas fazendo com que as sequências intrónicas fossem consideradas não funcionais. Os genes são compostos por exões interrompidos por intrões. Os intrões são sequências nucleotidicas não codificantes não sendo, portanto, traduzidos, uma vez que são removidos num processo anterior, denominado splicing. Foram identificadas diversas variantes de nucleotídeos localizadas profundamente nos intrões com associação significativa a doenças. Variantes intrónicas profundas são mutações que ocorrem a mais de 100 pares de bases dos limites exão-intrão. O cancro representa a primeira causa de morte nos países desenvolvidos e a segunda causa de morte nos países em desenvolvimento. Em 2019 o cancro colorretal foi a sexta causa de morte em Portugal. Esta neoplasia é caracterizada por ser uma doença do genoma que evolui e progride por um acumular de mutações somáticas, e alterações epigenéticas com ou sem hereditariedade. Assim, o objetivo deste trabalho é realizar uma análise exaustiva de mutações intrónicas profundas já identificadas e prever o efeito funcional dessas mutações através de uma análise in sílico. Através do programa bioinformático, foi possível obter dados e dividi-los em duas tabelas. A primeira tabela consiste nas variantes e genes já reportados clinicamente e a segunda tabela contém variantes que ainda não foram reportadas clinicamente. Existem várias variantes envolvidas no CRR e seria importante começar a estudar essas mutações, especificamente para este tipo de cancro, de modo a perceber se poderão, por exemplo, ser um biomarcador deste cancro.
ABSTRACT - The genomic sequence was, for many years, only associated with its ability to encode proteins causing the intronic sequences to be considered non-functional. Genes are made of exons interrupted by introns. Introns are non-coding nucleotide sequences and are therefore not translated, as they are removed in an earlier process called splicing. Several nucleotide variants located deep in introns with significant disease association have been identified. Deep intronic variants are mutations that occur more than 100 base pairs from the exon-intron boundaries. Cancer represents the leading cause of death in developed countries and the second leading cause of death in developing countries. In 2019 colorectal cancer was the sixth leading cause of death in Portugal. This neoplasm is characterized for being a disease of the genome that evolves and progresses through the accumulation of somatic mutations, and epigenetic alterations with or without heredity. Thus, the purpose of this study is to carry out an exhaustive analysis of already identified deep intronic mutations and to predict the functional effect of these mutations through an in silico analysis. Through a bioinformatics program, it was possible to obtain data and divide them into two tables. The first table consists of the variants and genes that have already been clinically reported and the second table contains variants that have not yet been clinically reported. There are several variants involved in CRR and it would be important to start studying these mutations, specifically for this type of cancer, in order to understand if they could, for example, be a biomarker of this cancer.
ABSTRACT - The genomic sequence was, for many years, only associated with its ability to encode proteins causing the intronic sequences to be considered non-functional. Genes are made of exons interrupted by introns. Introns are non-coding nucleotide sequences and are therefore not translated, as they are removed in an earlier process called splicing. Several nucleotide variants located deep in introns with significant disease association have been identified. Deep intronic variants are mutations that occur more than 100 base pairs from the exon-intron boundaries. Cancer represents the leading cause of death in developed countries and the second leading cause of death in developing countries. In 2019 colorectal cancer was the sixth leading cause of death in Portugal. This neoplasm is characterized for being a disease of the genome that evolves and progresses through the accumulation of somatic mutations, and epigenetic alterations with or without heredity. Thus, the purpose of this study is to carry out an exhaustive analysis of already identified deep intronic mutations and to predict the functional effect of these mutations through an in silico analysis. Through a bioinformatics program, it was possible to obtain data and divide them into two tables. The first table consists of the variants and genes that have already been clinically reported and the second table contains variants that have not yet been clinically reported. There are several variants involved in CRR and it would be important to start studying these mutations, specifically for this type of cancer, in order to understand if they could, for example, be a biomarker of this cancer.
Description
Mestrado em Tecnologias Clínico Laboratoriais
Keywords
Cancro colorretal Genética Intrões profundos Colorectal cancer Genetics Deep introns
Pedagogical Context
Citation
Luís MJ. Deep intronic mutations in colorretal cancer [dissertation]. Lisboa: Escola Superior de Tecnologia da Saúde de Lisboa/Instituto Politécnico de Lisboa; 2021.
Publisher
Instituto Politécnico de Lisboa, Escola Superior de Tecnologia da Saúde de Lisboa