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Epigenomic Convergence of Neural-Immune Risk Factors in Neurodevelopmental Disorder Cortex.

A Vogel Ciernia1, B I Laufer1, H Hwang1

  • 1Department of Medical Microbiology and Immunology, MIND Institute, Genome Center, University of California, Davis, CA 95616, USA.

Cerebral Cortex (New York, N.Y. : 1991)
|June 27, 2019
PubMed
Summary
This summary is machine-generated.

Epigenetic changes in the brain are linked to neurodevelopmental disorders (NDDs). This study identified specific DNA methylation patterns in NDDs, offering insights into disease mechanisms and potential therapeutic targets.

Keywords:
DNA methylationautism spectrum disordersepigeneticsmicroglianeurodevelopmental disorders

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Area of Science:

  • Neuroscience
  • Genetics
  • Epigenetics

Background:

  • Neurodevelopmental disorders (NDDs) affect a significant portion of children, leading to lifelong disabilities.
  • Epigenetic modifications, particularly DNA methylation, are crucial in understanding the interplay between genes and environmental factors in NDD etiology.

Purpose of the Study:

  • To investigate DNA cytosine methylation patterns in the human cortex across three distinct NDDs: autism spectrum disorder, Rett syndrome, and Dup15q syndrome.
  • To identify differentially methylated regions (DMRs) unique to each NDD and explore their shared regulatory functions.

Main Methods:

  • Whole-genome bisulfite sequencing was employed to analyze DNA methylation in 49 human cortex samples from individuals with NDDs and matched controls.
  • Integration of methylation data with genomic, genetic, and gene expression datasets.

Main Results:

  • Differentially methylated regions (DMRs) were identified, unique to each NDD but sharing regulatory functions in neurons and microglia.
  • NDD DMRs were enriched in promoter regions, transcription factor binding sites, and genes associated with nervous system development.
  • Genes linked to NDD DMRs indicated a role for altered microglial function in brain development.

Conclusions:

  • An epigenomic signature for NDDs in the human cortex has been identified.
  • These findings highlight the importance of microglial function in NDDs and suggest potential therapeutic targets and early biomarkers.