Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism

Simone Gupta, Shannon E. Ellis, Foram N. Ashar, Anna Moes, Joel S. Bader, Jianan Zhan, Andrew B. West, Dan Arking

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number5748
JournalNature Communications
Volume5
DOIs
StatePublished - 2014

Fingerprint

Gene Expression Profiling
Autistic Disorder
Innate Immunity
genes
brain
Brain
Genes
modules
etiology
sequencing
gene expression
immunity
Gene expression
complement
Chemical activation
activation
RNA
RNA Sequence Analysis
Gene Regulatory Networks
Microglia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. / Gupta, Simone; Ellis, Shannon E.; Ashar, Foram N.; Moes, Anna; Bader, Joel S.; Zhan, Jianan; West, Andrew B.; Arking, Dan.

In: Nature Communications, Vol. 5, 5748, 2014.

Research output: Contribution to journalArticle

Gupta, Simone ; Ellis, Shannon E. ; Ashar, Foram N. ; Moes, Anna ; Bader, Joel S. ; Zhan, Jianan ; West, Andrew B. ; Arking, Dan. / Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. In: Nature Communications. 2014 ; Vol. 5.
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