title: Decoding the contribution of dopaminergic genes and pathways to autism spectrum disorder (ASD).
abstract: Autism spectrum disorder (ASD) is a debilitating brain illness causing social deficits, delayed development and repetitive behaviors. ASD is a heritable neurodevelopmental disorder with poorly understood and complex etiology. The central dopaminergic system is strongly implicated in ASD pathogenesis. Genes encoding various elements of this system (including dopamine receptors, the dopamine transporter or enzymes of synthesis and catabolism) have been linked to ASD. Here, we comprehensively evaluate known molecular interactors of dopaminergic genes, and identify their potential molecular partners within up/down-steam signaling pathways associated with dopamine. These in silico analyses allowed us to construct a map of molecular pathways, regulated by dopamine and involved in ASD. Clustering these pathways reveals groups of genes associated with dopamine metabolism, encoding proteins that control dopamine neurotransmission, cytoskeletal processes, synaptic release, Ca(2+) signaling, as well as the adenosine, glutamatergic and gamma-aminobutyric systems. Overall, our analyses emphasize the important role of the dopaminergic system in ASD, and implicate several cellular signaling processes in its pathogenesis.
authors.affiliation: Department of Biomedical Engineering, University of Virginia, 415 Lane Road, Charlottesville, VA 22908, USA; ZENEREI Institute, 309 Palmer Court, Slidell, LA 70458, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Nguyen
authors.affiliation: School of Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Roth
authors.affiliation: College of Medicine, University of Illinois at Chicago, 808 S. Wood Street, Room 165 CME, M/C 783, Chicago, IL 60612, USA.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Kyzar
authors.affiliation: ZENEREI Institute, 309 Palmer Court, Slidell, LA 70458, USA.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Poudel
authors.affiliation: University of California San Diego (UCSD) School of Medicine, 9500 Gilman Dr, La Jolla, CA 92093, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Wong
authors.affiliation: ZENEREI Institute, 309 Palmer Court, Slidell, LA 70458, USA; Department of Neuroscience, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA 15260, USA.
authors.forename: Adam Michael
authors.initials: AM
authors.lastname: Stewart
authors.affiliation: ZENEREI Institute, 309 Palmer Court, Slidell, LA 70458, USA. Electronic address: avkalueff@gmail.com.
authors.forename: Allan V
authors.initials: AV
authors.lastname: Kalueff
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D004298:Dopamine / Q000235:genetics* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000502:physiology*; D006801:Humans; D009434:Neural Pathways / Q000502:physiology; D011954:Receptors, Dopamine / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; D004298:Dopamine
keywords: Autism; Dopaminergic system; Genetics; Molecular pathways; Translational research