title: SLC9A9 Co-expression modules in autism-associated brain regions.
abstract: SLC9A9 is a sodium hydrogen exchanger present in the recycling endosome and highly expressed in the brain. It is implicated in neuropsychiatric disorders, including autism spectrum disorders (ASDs). Little research concerning its gene expression patterns and biological pathways has been conducted. We sought to investigate its possible biological roles in autism-associated brain regions throughout development. We conducted a weighted gene co-expression network analysis on RNA-seq data downloaded from Brainspan. We compared prenatal and postnatal gene expression networks for three ASD-associated brain regions known to have high SLC9A9 gene expression. We also performed an ASD-associated single nucleotide polymorphism enrichment analysis and a cell signature enrichment analysis. The modules showed differences in gene constituents (membership), gene number, and connectivity throughout time. SLC9A9 was highly associated with immune system functions, metabolism, apoptosis, endocytosis, and signaling cascades. Gene list comparison with co-immunoprecipitation data was significant for multiple modules. We found a disproportionately high autism risk signal among genes constituting the prenatal hippocampal module. The modules were enriched with astrocyte and oligodendrocyte markers. SLC9A9 is potentially involved in the pathophysiology of ASDs. Our investigation confirmed proposed functions for SLC9A9, such as endocytosis and immune regulation, while also revealing potential roles in mTOR signaling and cell survival.. By providing a concise molecular map and interactions, evidence of cell type and implicated brain regions we hope this will guide future research on SLC9A9. Autism Res 2017, 10: 414-429. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
authors.affiliation: Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, New York.
authors.forename: Jameson
authors.initials: J
authors.lastname: Patak
authors.affiliation: Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, New York.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Hess
authors.affiliation: Department of Psychiatry, Upstate Medical University, Syracuse, New York.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang-James
authors.affiliation: Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, New York.|Department of Psychiatry, Upstate Medical University, Syracuse, New York.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Glatt
authors.affiliation: Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, New York.|Department of Psychiatry, Upstate Medical University, Syracuse, New York.|Department of Biomedicine, K.G. Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, Bergen, Norway.
authors.forename: Stephen V
authors.identifier: http://orcid.org/0000-0002-9217-3982
authors.initials: SV
authors.lastname: Faraone
mesh_terms: D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics* / Q000378:metabolism*
chemical_list: C478541:SLC9A9 protein, human; D017923:Sodium-Hydrogen Exchangers
keywords: Autism spectrum disorder; SLC9A9; endosomal pathway; transcriptome; weighted gene co-expression network analysis