Jul 19, 2016

Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder

BioRxiv : the Preprint Server for Biology
Michael V LombardoTiziano Pramparo

Abstract

Maternal immune activation (MIA) via infection during pregnancy is known to increase risk for autism spectrum disorder (ASD). However, it is unclear how MIA disrupts fetal brain gene expression in ways that may explain this increased risk. Here we examine how MIA dysregulates fetal brain gene expression near the end of the first trimester of human gestation in ways relevant to ASD-associated pathophysiology. MIA downregulates expression of ASD- associated genes, with the largest enrichments in genes known to harbor rare highly penetrant mutations. MIA also downregulates expression of many genes also known to be persistently downregulated in ASD cortex later in life and which are canonically known for roles in affecting prenatally-late developmental processes at the synapse. Transcriptional and translational programs that are downstream targets of highly ASD-penetrant FMR1 and CHD8 genes are also heavily affected by MIA. MIA strongly upregulates expression of a large number of genes involved in translation initiation, cell cycle, DNA damage, and proteolysis processes that affect multiple key neural developmental functions. Upregulation of translation initiation is common to and preserved in gene network structure with the ASD co...Continue Reading

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Mentioned in this Paper

Transcriptional Regulation
Cortex Bone Disorders
Adrenal Cortex Diseases
Fmr1
Tsc2
Genes
TSC2 gene
Eif4e
EIF4E gene
Transcription, Genetic

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