1. G72 primate-specific gene: a still enigmatic element in psychiatric disorders.
- Author
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Sacchi S, Binelli G, and Pollegioni L
- Subjects
- Animals, Bipolar Disorder genetics, Chromosomes, Human, Pair 13, Genetic Linkage, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins, Magnetic Resonance Imaging, Mental Disorders metabolism, Mice, Mice, Transgenic, Polymorphism, Single Nucleotide, Protein Structure, Tertiary, Psychotic Disorders genetics, Recombinant Proteins genetics, Schizophrenia genetics, Carrier Proteins genetics, Carrier Proteins physiology, Gene Expression Regulation, Mental Disorders genetics
- 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.
- Published
- 2016
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