Towards a molecular characterization of autism spectrum disorders: An exome sequencing and systems approach

Joon-Yong An, Alexandre Santos Cristino, Qiongyi Zhao, Janette Edson, Sarah M Williams, David Ravine, John Wray, Vikki Maree Marshall, Anna Hunt, Andrew Joseph Orgar Whitehouse, Charles Claudianos

Research output: Contribution to journalArticleResearchpeer-review

47 Citations (Scopus)


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
Number of pages9
JournalTranslational Psychiatry
Issue number6
Publication statusPublished - 3 Jun 2014
Externally publishedYes

Cite this