Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism
Nature Communications 5, Article number: 5748 doi:10.1038/ncomms6748 Received 28 September 2014 Accepted 03 November 2014 Published 10 December 2014 Department of Medicine, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Simone Gupta, Shannon E. Ellis, Foram N. Ashar, Anna Moes, Joel S. Bader Dan E. Arking Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA Joel S. Bader & Jianan Zhan Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA Andrew B. West
Abstract
Recent studies of genomic variation associated with autism have suggested the existence of extreme heterogeneity. Large-scale transcriptomics should complement these results to identify core molecular pathways underlying autism. Here we report results from a large-scale RNA sequencing effort, utilizing region-matched autism and control brains to identify neuronal and microglial genes robustly dysregulated in autism cortical brain. Remarkably, we note that a gene expression module corresponding to M2-activation states in microglia is negatively correlated with a differentially expressed neuronal module, implicating dysregulated microglial responses in concert with altered neuronal activity-dependent genes in autism brains. These observations provide pathways and candidate genes that highlight the interplay between innate immunity and neuronal activity in the aetiology of autism.
