Identification of amygdala-expressed genes associated with autism spectrum disorder

Mol Autism. 2020 May 27;11(1):39. doi: 10.1186/s13229-020-00346-1.


Background: Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implicating complex genetics and involvement of a variety of brain regions. However, how mutations and mis-expression of select gene sets are associated with the behavioral components of ASD remains unknown. We reasoned that for genes to be associated with ASD core behaviors they must be: (1) expressed in brain regions relevant to ASD social behaviors and (2) expressed during the ASD susceptible window of brain development.

Methods: Focusing on the amygdala, a brain region whose dysfunction has been highly implicated in the social component of ASD, we mined publicly available gene expression databases to identify ASD-susceptibility genes expressed during human and mouse amygdala development. We found that a large cohort of known ASD susceptibility genes is expressed in the developing human and mouse amygdala. We further performed analysis of single-nucleus RNA-seq (snRNA-seq) data from microdissected amygdala tissue from five ASD and five control human postmortem brains ranging in age from 4 to 20 years to elucidate cell type specificity of amygdala-expressed genes and their dysregulation in ASD.

Results: Our analyses revealed that of the high-ranking ASD susceptibility genes, 80 are expressed in both human and mouse amygdala during fetal to early postnatal stages of development. Our human snRNA-seq analyses revealed cohorts of genes with altered expression in the ASD amygdala postnatally, especially within excitatory neurons, with dysregulated expression of seven genes predicted from our datamining pipeline.

Limitations: We were limited by the ages for which we were able to obtain human tissue; therefore, the results from our datamining pipeline approach will require validation, to the extent possible, in human tissue from earlier developmental stages.

Conclusions: Our pipeline narrows down the number of amygdala-expressed genes possibly involved in the social pathophysiology of ASD. Our human single-nucleus gene expression analyses revealed that ASD is characterized by changes in gene expression in specific cell types in the early postnatal amygdala.

Keywords: ASD genes; Amygdala; Autism spectrum disorder; Brain development; Single nucleus RNA sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amygdala / metabolism*
  • Amygdala / physiopathology
  • Animals
  • Autism Spectrum Disorder / etiology*
  • Autism Spectrum Disorder / metabolism
  • Biomarkers*
  • Brain / metabolism
  • Brain / physiopathology
  • Computational Biology / methods
  • Databases, Genetic
  • Disease Susceptibility*
  • Gene Expression
  • Gene Expression Profiling
  • Gene Ontology
  • Gene Regulatory Networks
  • Genetic Predisposition to Disease
  • Humans
  • Mice
  • Signal Transduction
  • Transcriptome


  • Biomarkers