title: The role of protein intrinsic disorder in major psychiatric disorders.
abstract: Although new candidate genes for Autism Spectrum Disorder (ASD), Schizophrenia (SCZ), Attention-Deficit/Hyperactivity Disorder (ADHD), and Bipolar Disorder (BD) emerged from genome-wide association studies (GWAS), their underlying molecular mechanisms remain poorly understood. Evidences of the involvement of intrinsically disordered proteins in diseases have grown in the last decade. These proteins lack tridimensional structure under physiological conditions and are involved in important cellular functions such as signaling, recognition and regulation. The aim of the present study was to identify the role and abundance of intrinsically disordered proteins in a set of psychiatric diseases and to test whether diseases are different regarding protein intrinsic disorder. Our hypothesis is that differences across psychiatric illnesses phenotypes and symptoms may arise from differences in intrinsic protein disorder content and properties of each group. A bioinformatics prediction of intrinsic disorder was performed in proteins retrieved based on top findings from GWAS, Copy Number Variation and candidate gene investigations for each disease. This approach revealed that about 80% of studied proteins presented long stretches of disorder. This amount was significantly higher than that observed in general eukaryotic proteins, and those involved in cardiovascular diseases. These results suggest that proteins with intrinsic disorder are a common feature of neurodevelopment and synaptic transmission processes which are potentially involved in the etiology of psychiatric diseases. Moreover, we identified differences between ADHD and ASD when the binary prediction of structure and putative binding sites were compared. These differences may be related to variation in symptom complexity between both diseases. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.|Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, RS, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Tovo-Rodrigues
authors.affiliation: Experimental and Molecular Cardiovascular Laboratory, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Recamonde-Mendoza
authors.affiliation: Postgraduate Program in Genetics and Biodiversity, Federal University of Bahia (UFBA), Salvador, BA, Brazil.
authors.forename: Vanessa Rodrigues
authors.initials: VR
authors.lastname: Paixão-Côrtes
authors.affiliation: Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Estela M
authors.initials: EM
authors.lastname: Bruxel
authors.affiliation: Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Jaqueline B
authors.initials: JB
authors.lastname: Schuch
authors.affiliation: Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Deise C
authors.initials: DC
authors.lastname: Friedrich
authors.affiliation: Child and Adolescent Psychiatric Division, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.|National Institute of Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Rohde
authors.affiliation: Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Mara H
authors.initials: MH
authors.lastname: Hutz
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D000067877:Autism Spectrum Disorder / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics; D056915:DNA Copy Number Variations; D030561:Databases, Nucleic Acid; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D001523:Mental Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D057165:Proteostasis Deficiencies / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics
keywords: intrinsic disorder; neurodevelopment; protein-protein interaction; psychiatric disorders