Print Email Facebook Twitter Shared Pathways Among Autism Candidate Genes Determined by Co-expression Network Analysis of the Developing Human Brain Transcriptome Title Shared Pathways Among Autism Candidate Genes Determined by Co-expression Network Analysis of the Developing Human Brain Transcriptome Author Mahfouz, A. Ziats, M.N. Rennert, O.M. Lelieveldt, B.P.F. Reinders, M.J.T. Faculty Electrical Engineering, Mathematics and Computer Science Department Intelligent Systems Date 2015-09-23 Abstract Autism spectrum disorder (ASD) is a neurodevelopmental syndrome known to have a significant but complex genetic etiology. Hundreds of diverse genes have been implicated in ASD; yet understanding how many genes, each with disparate function, can all be linked to a single clinical phenotype remains unclear. We hypothesized that understanding functional relationships between autism candidate genes during normal human brain development may provide convergent mechanistic insight into the genetic heterogeneity of ASD. We analyzed the co-expression relationships of 455 genes previously implicated in autism using the BrainSpan human transcriptome database, across 16 anatomical brain regions spanning prenatal life through adulthood. We discovered modules of ASD candidate genes with biologically relevant temporal co-expression dynamics, which were enriched for functional ontologies related to synaptogenesis, apoptosis, and GABA-ergic neurons. Furthermore, we also constructed co-expression networks from the entire transcriptome and found that ASD candidate genes were enriched in modules related to mitochondrial function, protein translation, and ubiquitination. Hub genes central to these ASD-enriched modules were further identified, and their functions supported these ontological findings. Overall, our multi-dimensional co-expression analysis of ASD candidate genes in the normal developing human brain suggests the heterogeneous set of ASD candidates share transcriptional networks related to synapse formation and elimination, protein turnover, and mitochondrial function. Subject autism spectrum disordergene co-expression networksynaptogenesismitochondrionapoptosis To reference this document use: http://resolver.tudelft.nl/uuid:00359bfe-96ac-4dfe-b544-9559131f0d1e Publisher Springer ISSN 0895-8696 Source https://doi.org/10.1007/s12031-015-0641-3 Source Journal of Molecular Neuroscience, 2015 Part of collection Institutional Repository Document type journal article Rights (c) 2015 The Author(s)This article is published with open access at Springerlink.com Files PDF Mahfouz_2015.pdf 5.05 MB Close viewer /islandora/object/uuid:00359bfe-96ac-4dfe-b544-9559131f0d1e/datastream/OBJ/view