title: G72 primate-specific gene: a still enigmatic element in psychiatric disorders.
abstract: Numerous studies have demonstrated a link between genetic markers on chromosome 13 and schizophrenia, bipolar affective disorder, and other psychiatric phenotypes. The G72/G30 genes (transcribed in opposite directions) are located on chromosome 13q33, a region demonstrating strong evidence for linkage with various neuropsychiatric disorders. G72/G30 was identified in 2002 as a schizophrenia susceptibility locus; however, subsequent association studies did not reach consensus on single SNPs within the locus. Simultaneously, a new vision for the genetic architecture of psychiatric disorders suggested that schizophrenia was a quantitative trait, therefore ascribable to potentially hundreds of genes and subjected to the vagaries of the environment. The main protein product of G72 gene is named pLG72 or D-amino acid oxidase activator DAOA (153 amino acids) and its function is still debated. Functional analyses, also showing controversial results, indicate that pLG72 contributes to N-methyl-D-aspartate receptor modulation by affecting activity of the flavoprotein D-amino acid oxidase, the enzyme responsible for degrading the neuromodulator D-serine. In this review we, for the first time, summarize findings from molecular genetic linkage and association studies concerning G72 gene, cellular and molecular studies on pLG72, and investigations performed on G72/G30 transgenic mice. This will help elucidate the role of psychosis susceptibility genes, which will have a major impact on our understanding of disease pathophysiology and thus change classification and treatment.
authors.affiliation: Dipartimento di Biotecnologie e Scienze della Vita, Università degli studi dell'Insubria, via J. H. Dunant 3, 21100, Varese, Italy.|The Protein Factory, Centro Interuniversitario di Biotecnologie Proteiche, Università degli studi dell'Insubria and Politecnico di Milano, Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sacchi
authors.affiliation: Dipartimento di Biotecnologie e Scienze della Vita, Università degli studi dell'Insubria, via J. H. Dunant 3, 21100, Varese, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Binelli
authors.affiliation: Dipartimento di Biotecnologie e Scienze della Vita, Università degli studi dell'Insubria, via J. H. Dunant 3, 21100, Varese, Italy. loredano.pollegioni@uninsubria.it.|The Protein Factory, Centro Interuniversitario di Biotecnologie Proteiche, Università degli studi dell'Insubria and Politecnico di Milano, Milano, Italy. loredano.pollegioni@uninsubria.it.
authors.forename: Loredano
authors.initials: L
authors.lastname: Pollegioni
mesh_terms: D000818:Animals; D001714:Bipolar Disorder / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D002882:Chromosomes, Human, Pair 13; D005786:Gene Expression Regulation; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008279:Magnetic Resonance Imaging; D001523:Mental Disorders / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D011618:Psychotic Disorders / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins
keywords: D-Serine; DAOA; Molecular basis; NMDA receptors; Schizophrenia; pLG72