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

Author

Listed:
  • Simone Gupta

    (McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine)

  • Shannon E. Ellis

    (McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine)

  • Foram N. Ashar

    (McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine)

  • Anna Moes

    (McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine)

  • Joel S. Bader

    (McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Jianan Zhan

    (Johns Hopkins University School of Medicine)

  • Andrew B. West

    (University of Alabama at Birmingham)

  • Dan E. Arking

    (McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine)

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.

Suggested Citation

  • Simone Gupta & Shannon E. Ellis & Foram N. Ashar & Anna Moes & Joel S. Bader & Jianan Zhan & Andrew B. West & Dan E. Arking, 2014. "Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism," Nature Communications, Nature, vol. 5(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6748
    DOI: 10.1038/ncomms6748
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    Cited by:

    1. Fan, Jianqing & Guo, Yongyi & Jiang, Bai, 2022. "Adaptive Huber regression on Markov-dependent data," Stochastic Processes and their Applications, Elsevier, vol. 150(C), pages 802-818.

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