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

An, J. Y., Cristino, A. S., Zhao, Q., Edson, J., Williams, S. M., Ravine, D., Wray, J., Marshall, V. M., Hunt, A., Whitehouse, A. J. O. and Claudianos, C. (2014) Towards a molecular characterization of autism spectrum disorders: an exome sequencing and systems approach. Translational Psychiatry, 4 e394.1-e394.9. doi:10.1038/tp.2014.38

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Author An, J. Y.
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.
Title Towards a molecular characterization of autism spectrum disorders: an exome sequencing and systems approach
Journal name Translational Psychiatry   Check publisher's open access policy
ISSN 2158-3188
Publication date 2014-06-03
Sub-type Article (original research)
DOI 10.1038/tp.2014.38
Open Access Status DOI
Volume 4
Start page e394.1
End page e394.9
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 2738 Psychiatry and Mental health
2803 Biological Psychiatry
2804 Cellular and Molecular Neuroscience
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
 
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