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Epigenetic inheritance of Autism Spectrun Disorder (ASD): possible role of sncRNA

Abstract

Epigenetics refers to the modulation on gene expression and on DNA structure that are not related to alterations of base sequence. These type of modulation of gene expression include DNA methylation and regulation through short non-coding RNAs (sncRNA). The sncRNA have been pointed as potential biomarkers for psychiatric disorders. The Autism Spectrum Disorder (ASD) is developmental neurologic disorder that involves a broad spectrum of phenotypes and that show complex genetic contribution. Although ASD heritability has been indicated, clear and defined genetic patterns to identify ASD inheritance have not been established so far. Mechanisms of epigenetic inheritance are being identified in the transmission of stress memory and in the transmission of the increase of synaptic plasticity. Considering this, we raise the hypothesis that the combination of genetic and epigenetic landscape might influence ASD development and manifestation. Thus, the aim of this study is to investigate possible alterations of sncRNA profile in neurons derived from iPSC of ASD when compared with control neurons, and then compare it with sncRNA profile in the sperm of the patients' fathers. ASD patients and their fathers will be recruited and their blood will be collected. Semen samples from the fathers and from control individuals will also be collected. iPSC will be obtained from the PBMC and will be differentiated into neural progenitor cells (NPC) and neurons. The neurons, the NPC and the sperm will be submitted to RNA extraction and the sncRNA will be analyzed through next generation sequencing the sncRNA that show differential expression and that show relevance for this study will be validated by RT-qPCR. (AU)

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