Brain transcriptional and epigenetic associations with autism

PLoS One. 2012;7(9):e44736. doi: 10.1371/journal.pone.0044736. Epub 2012 Sep 12.


Background: Autism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic.

Methodology/principal findings: To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and whole genome DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling.

Conclusions/significance: This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autistic Disorder / genetics*
  • Brain / pathology
  • Child
  • Child, Preschool
  • DNA Methylation
  • Epigenesis, Genetic*
  • Fragile X Syndrome / genetics
  • Gene Dosage
  • Gene Expression Regulation
  • Humans
  • Infant
  • Inflammation
  • Male
  • Middle Aged
  • Mitochondria / metabolism
  • Models, Statistical
  • Myelin Sheath / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Phosphorylation
  • Phenotype
  • Protein Biosynthesis
  • Sequence Analysis, DNA
  • Signal Transduction
  • Transcription, Genetic*

Associated data

  • GEO/GSE38322
  • GEO/GSE38608