Percorrer por autor "Marques, Ana Rita"
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- Bridging genetic insights with neuroimaging in Autism Spectrum Disorder — A systematic reviewPublication . Vilela, Joana; Rasga, Célia; Santos, João Xavier; Martiniano, Hugo; Marques, Ana Rita; Oliveira, Guiomar; Vicente, Astrid Moura; Maria Rasga, CéliaAutism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of behavior. Family studies show that ASD is highly heritable, and hundreds of genes have previously been implicated in the disorder; however, the etiology is still not fully clear. Brain imaging and electroencephalography (EEG) are key techniques that study alterations in brain structure and function. Combined with genetic analysis, these techniques have the potential to help in the clarification of the neurobiological mechanisms contributing to ASD and help in defining novel therapeutic targets. To further understand what is known today regarding the impact of genetic variants in the brain alterations observed in individuals with ASD, a systematic review was carried out using Pubmed and EBSCO databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review shows that specific genetic variants and altered patterns of gene expression in individuals with ASD may have an effect on brain circuits associated with face processing and social cognition, and contribute to excitation–inhibition imbalances and to anomalies in brain volumes.
- Identification of neurotransmission and synaptic biological processes Disrupted in Autism Spectrum Disorder using interaction networks and community detection analysisPublication . Vilela, Joana; Martiniano, Hugo; Marques, Ana Rita; Santos, João Xavier; Asif, Muhammad; Rasga, Célia; Oliveira, Guiomar; Vicente, Astrid Moura; Maria Rasga, CéliaAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by communication deficits and repetitive behavioral patterns. Hundreds of candidate genes have been implicated in ASD, including neurotransmission and synaptic (NS) genes; however, the genetic architecture of this disease is far from clear. In this study, we seek to clarify the biological processes affected by NS gene variants identified in individuals with ASD and the global networks that link those processes together. For a curated list of 1216 NS candidate genes, identified in multiple databases and the literature, we searched for ultra-rare (UR) loss-of-function (LoF) variants in the whole-exome sequencing dataset from the Autism Sequencing Consortium (N = 3938 cases). Filtering for population frequency was carried out using gnomAD (N = 60,146 controls). NS genes with UR LoF variants were used to construct a network of protein–protein interactions, and the network’s biological communities were identified by applying the Leiden algorithm. We further explored the expression enrichment of network genes in specific brain regions. We identified 356 variants in 208 genes, with a preponderance of UR LoF variants in the PDE11A and SYTL3 genes. Expression enrichment analysis highlighted several subcortical structures, particularly the basal ganglia. The interaction network defined seven network communities, clustering synaptic and neurotransmitter pathways with several ubiquitous processes that occur in multiple organs and systems. This approach also uncovered biological pathways that are not usually associated with ASD, such as brain cytochromes P450 and brain mitochondrial metabolism. Overall, the community analysis suggests that ASD involves the disruption of synaptic and neurotransmitter pathways but also ubiquitous, but less frequently implicated, biological processes.