Single Nucleotide Variant (SNV) analysis in Autism Spectrum Disorder

Vilela, Joana

http://hdl.handle.net/10400.18/8281

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Vilela, Joana

Abstract(s)

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by communication deficits and repetitive behavioral patterns of variable degrees of clinical severity, and an important genetic component. There is strong evidence indicating that neurotransmission and synaptic processes are altered in ASD. Our objective was to identify ultra-rare variants in neurotransmission and synaptic (NS) genes that play a role in ASD, linking mutations to the biological pathways affected. We identified 357 variants in 208 genes in the ASD dataset, defining 7 network communities: Cytochrome P450 metabolism; Ion channel activity; Chemical synapse transmission; Neuronal development; G protein-coupled receptors; Energy metabolism and Neurotransmitter release cycle. The neuronal development community (27,6% of network cases; 54 genes), the Cytochrome P450 metabolism community (18,8% of network cases; 33 genes) and the G protein-coupled receptors community (16,1% of network cases; 32 genes), are the biological communities with the highest number of cases affected by ultra-rare SNVs in the network analysed. The majority of the network cases analyzed has mutations in genes involved in neuronal development, supporting the relevance of this pathway in ASD. This study reinforces the synaptic and neurotransmitter pathway hypothesis as one of the disease-relevant genetic drivers for ASD.