Towards a molecular characterization of autism spectrum disorders

An exome sequencing and systems approach

Joon-Yong An, A. S. Cristino, Q. Zhao, J. Edson, S. M. Williams, D. Ravine, J. Wray, V. M. Marshall, A. Hunt, A. J.O. Whitehouse, C. Claudianos

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The hypothetical 'AXAS' gene network model that profiles functional patterns of heterogeneous DNA variants overrepresented in autism spectrum disorder (ASD), X-linked intellectual disability, attention deficit and hyperactivity disorder and schizophrenia was used in this current study to analyze whole exome sequencing data from an Australian ASD cohort. An optimized DNA variant filtering pipeline was used to identify loss-of-function DNA variations. Inherited variants from parents with a broader autism phenotype and de novo variants were found to be significantly associated with ASD. Gene ontology analysis revealed that putative rare causal variants cluster in key neurobiological processes and are overrepresented in functions involving neuronal development, signal transduction and synapse development including the neurexin trans-synaptic complex. We also show how a complex gene network model can be used to fine map combinations of inherited and de novo variations in families with ASD that converge in the L1CAM pathway. Our results provide an important step forward in the molecular characterization of ASD with potential for developing a tool to analyze the pathogenesis of individual affected families.

Original languageEnglish
Article numbere394
JournalTranslational psychiatry
Volume4
DOIs
Publication statusPublished - 2014 Jun 3
Externally publishedYes

Fingerprint

Exome
Systems Analysis
Gene Regulatory Networks
DNA
Neural Cell Adhesion Molecule L1
Gene Ontology
Attention Deficit Disorder with Hyperactivity
Autistic Disorder
Intellectual Disability
Synapses
Signal Transduction
Schizophrenia
Autism Spectrum Disorder
Phenotype

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Towards a molecular characterization of autism spectrum disorders : An exome sequencing and systems approach. / An, Joon-Yong; Cristino, A. S.; Zhao, Q.; Edson, J.; Williams, S. M.; Ravine, D.; Wray, J.; Marshall, V. M.; Hunt, A.; Whitehouse, A. J.O.; Claudianos, C.

In: Translational psychiatry, Vol. 4, e394, 03.06.2014.

Research output: Contribution to journalArticle

An, J-Y, Cristino, AS, Zhao, Q, Edson, J, Williams, SM, Ravine, D, Wray, J, Marshall, VM, Hunt, A, Whitehouse, AJO & Claudianos, C 2014, 'Towards a molecular characterization of autism spectrum disorders: An exome sequencing and systems approach', Translational psychiatry, vol. 4, e394. https://doi.org/10.1038/tp.2014.38
An, Joon-Yong ; Cristino, A. S. ; Zhao, Q. ; Edson, J. ; Williams, S. M. ; Ravine, D. ; Wray, J. ; Marshall, V. M. ; Hunt, A. ; Whitehouse, A. J.O. ; Claudianos, C. / Towards a molecular characterization of autism spectrum disorders : An exome sequencing and systems approach. In: Translational psychiatry. 2014 ; Vol. 4.
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