Browsing by Author "Moura Vicente, Astrid"
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- 1M Genomas Europeus: ganhos e desafiosPublication . Moura Vicente, AstridMedicina personalisada: A medicina personalizada é amplamente entendida como um modelo médico que utiliza a caracterização dos fenótipos e genótipos das pessoas (por exemplo, a caracterização molecular, a imagiologia médica, dados relativos ao estilo de vida) para ajustar a estratégia terapêutica a cada pessoa no momento certo, e/ou para determinar a predisposição a doenças e/ou para prestar cuidados preventivos atempados e devidamente direcionados. Conclusões do Conselho da União Europeia sobre a medicina personalizada para os doentes (2015/C 421/03)
- Autism Genome ProjectPublication . Moura Vicente, Astrid
- Autism Spectrum DisorderPublication . Moura Vicente, Astrid; Vilela, Joana; Marques, Ana Rita1) Identification of neurotransmitter and synaptic gene variants in ASD patients; 2) Are genetic variants targeting noncoding RNAs contributing to ASD risk?; 3) An integrative system biology approach to delineate complex genotype-phenotype associations in ASD; 4) Mining of genes relevant for ASD in large databases.
- Autism Spectrum Disorder: contribution of genetic variants involved in the nonsense-mediated mRNA decayPublication . Marques, Ana Rita; Santos, João Xavier; Vilela, Joana; Rasga, Célia; Martiniano, Hugo; Oliveira, Guiomar; Romão, Luísa; Moura Vicente, AstridIntroduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impairedsocial/communication skills and stereotyped/repetitive behaviors. Genetic factors account for 50-80% of the familialrisk of ASD, but genetic determinants are not fully understood and a role for regulatory processes is plausible. Inthis study, we explored the contribution to ASD etiology of genes involved in an important post-transcriptionalregulatory mechanism implicated in neurodevelopment, the Nonsense-Mediated Decay (NMD). Methods: We first compiled a group of 46 genes encoding NMD factors and regulators. In these genes wesearched for Single Nucleotide Variants (SNVs) and Copy Number Variants (CNVs) in two samples of ASD patients(N=1828 and N=3570, respectively). We observed the frequency of these variants in 60146 controls from gnomADv2.1.1 (for SNVs) and in 10355 controls from the Database of Genomic Variant ( for CNVs). In genes with rarevariants (MAF<1% in controls) predicted to be pathogenic in silico , we further investigated whether these variantsaffect protein domains required for NMD. Results: We identified 270 predicted pathogenic SNVs within 38 genes in 524 ASD patients (28.7% of the total ASDcases) and 38 CNVs located in 18 genes in 38 ASD patients (1% of the ASD cases). Five of these genes, RBM8A , UPF2 , FMR1 , SMG6 and EIF4G1, were previously associated with ASD. We found that 136 variants (122 SNVsand 11 CNVs), in 23 genes, were located within known protein domainsrequired for NMD. These variants, identifiedin 258 ASD patients, may affect proper NMD function and consequently contribute to changes in the expression ofNMD targets. Discussion : In this study we identified genetic variants that may affect NMD function in ASD patients. Since mostNMD targets encode proteins expressed in the brain, we hypothesize that NMD impairment can constitute a riskfactor to ASD pathophysiology. Further studies are needed to better understand the impact of these genetic variantson NMD function and their relevance for ASD.A full understanding of these regulatory mechanisms may constitutean opportunity for the development of therapeutic interventions.
- O AutismoPublication . Moura Vicente, Astrid; Conceição, Inês; Miranda, Natércia; Bourbon, Mafalda; Rasga, CéliaDe acordo com os manuais médicos, o autismo, ou a Perturbação do Espetro do Autismo (PEA), é uma condição médica do sistema nervoso central que se manifesta na infância e que se caracteriza por dificuldades na comunicação e interação social e por comportamentos, interesses ou atividades repetitivos e estereotipados.
- CNV selection in 342 Portuguese individuals genotyped by the AGPPublication . Moura Vicente, Astrid
- Doenças CardiovascularesPublication . Bourbon, Mafalda; Miranda, Natercia; Moura Vicente, Astrid; Rato, QuitériaAs doenças cardiovasculares (cardio = coração; vasculares = vasos sanguíneos) afetam o sistema circulatório, ou seja, o coração e os vasos sanguíneos (artérias, veias e vasos capilares). As doenças cardiovasculares (DCV) são de vários tipos, sendo as mais preocupantes a doença das artérias coronárias (artérias do coração) e a doença das artérias do cérebro. Quase todas são provocadas por aterosclerose, ou seja, pelo depósito de placas de gordura e cálcio no interior das artérias que dificultam a circulação sanguínea nos órgãos e podem mesmo chegar a impedi-la. Quando a aterosclerose aparece nas artérias coronárias, pode causar sintomas e doenças como a angina de peito, ou provocar um enfarte do miocárdio. Quando se desenvolve nas artérias do cérebro, pode originar sintomas como, por exemplo, alterações de memória, tonturas ou causar um acidente vascular cerebral (AVC). Sabia que o enfarte do miocárdio e o AVC são uma das principais causas de morte em Portugal? Pois, é verdade. Mas a situação pode ser alterada, já que estas doenças podem ser prevenidas pela adoção de um estilo de vida saudável e vigilância médica regular.
- Estudo Longitudinal da Exposição Ambiental a Toxinas (ELEAT): interações gene-ambiente na Perturbação do Espetro do AutismoPublication . Moura Vicente, AstridSobre interações gene-ambiente na Perturbação do Espetro do Autismo.
- Evidence for an association of prenatal exposure to particulate matter with clinical severity of Autism Spectrum DisorderPublication . Santos, João Xavier; Sampaio, Pedro; Rasga, Célia; Martiniano, Hugo; Faria, Clarissa; Café, Cátia; Oliveira, Alexandra; Duque, Frederico; Oliveira, Guiomar; Sousa, Lisete; Nunes, Ana; Moura Vicente, AstridEarly-life exposure to air pollutants, including ozone (O3), particulate matter (PM2.5 or PM10, depending on diameter of particles), nitrogen dioxide (NO2) and sulfur dioxide (SO2) has been suggested to contribute to the etiology of Autism Spectrum Disorder (ASD). In this study, we used air quality monitoring data to examine whether mothers of children with ASD were exposed to high levels of air pollutants during critical periods of pregnancy, and if higher exposure levels may lead to a higher clinical severity in their offspring. We used public data from the Portuguese Environment Agency to estimate exposure to these pollutants during the first, second and third trimesters of pregnancy, full pregnancy and first year of life of the child, for 217 subjects with ASD born between 2003 and 2016. These subjects were stratified in two subgroups according to clinical severity, as defined by the Autism Diagnostic Observational Schedule (ADOS). For all time periods, the average levels of PM2.5, PM10 and NO2 to which the subjects were exposed were within the admissible levels defined by the European Union. However, a fraction of these subjects showed exposure to levels of PM2.5 and PM10 above the admissible threshold. A higher clinical severity was associated with higher exposure to PM2.5 (p = 0.001), NO2 (p = 0.011) and PM10 (p = 0.041) during the first trimester of pregnancy, when compared with milder clinical severity. After logistic regression, associations with higher clinical severity were identified for PM2.5 exposure during the first trimester (p = 0.002; OR = 1.14, 95%CI: 1.05–1.23) and full pregnancy (p = 0.04; OR = 1.07, 95%CI: 1.00–1.15) and for PM10 (p = 0.02; OR = 1.07, 95%CI: 1.01–1.14) exposure during the third trimester. Exposure to PM is known to elicit neuropathological mechanisms associated with ASD, including neuroinflammation, mitochondrial disruptions, oxidative stress and epigenetic changes. These results offer new insights on the impact of earlylife exposure to PM in ASD clinical severity.
- Exploring mechanisms of gene-environment interactions contributing to the onset of idiopathic Autism Spectrum DisorderPublication . Xavier Santos, João; Martiniano, Hugo; Marques, Ana Rita; Rasga, Célia; Vilela, Joana; Moura Vicente, AstridSequencing studies have yielded several candidate genes for Autism Spectrum Disorder (ASD). However, the biological mechanisms underlying its onset are still unclear. Environmental factors may modulate ASD risk, with heritability estimates of 50-80% supporting a role for gene-environment interactions in idiopathic cases. We hypothesize that ASD candidate genes interact with reported ubiquitous environmental risk factors. Thus, we interrogated the Comparative Toxicogenomics Database (CTD) for interactions between 1144 ASD candidate genes and 59 ASD-risk chemicals. A proportion analysis was performed to identify genes that selectively interact with ASD risk chemicals (and vice-versa). Genetic data from ASD-individuals was inspected to identify SNVs (n=2674) and CNVs (n=3570). Eleven genes, including genes encoding for sex hormone receptors (AR, ESR1 and ESR2), signaling kinases (MAPK1 and MAPK3) and xenobiotics-responding molecules (GSTM1 and SLC7A5) were found to selectively interact with ASD-chemicals. Meanwhile, heavy metals, endocrine disruptors (pesticides, benzo(a)pyrene and a phthalate) and valproic acid were found to selectively target ASD-candidate genes. In ASD-cases, we found 22 loss-of-function or deleterious missense SNVs in 8/11 genes, of which 3 (ESR1, ESR2, and MAPK3) were also targeted by CNVs. External cues may dysregulate the MAPK signaling cascade, leading to neurodevelopmental problems. Hormone-mimicking toxins act as agonist/antagonist ligands to hormone receptors, while SLC7A5 is a blood-brain barrier (BBB) transporter. Sex hormones and BBB are fundamental during early development. We highlight the need of considering genetics and environment as interacting entities. Efforts to collect early-life exposure data from genetically susceptible patients may accelerate the implementation of health management strategies for ASD.