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G72 primate-specific gene: a still enigmatic element in psychiatric disorders

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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.

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Abbreviations

BAC :

Bacterial artificial chromosome

BOLD :

Blood oxygen level-dependent

CNS :

Central nervous system

CPZ :

Chlorpromazine

DAAO :

d-Amino acid oxidase

FA :

Fractional anisotropy

fMRI :

Functional magnetic resonance imaging

GWAS :

Genome-wide association studies

hDAAO :

Human d-amino acid oxidase

MRSB2 :

Mitochondrial methionine-R-sulfoxide reductase B2

MTG :

Middle temporal gyrus

NLS :

N-Lauroylsarcosine

NMDAR :

N-Methyl-d-aspartate type glutamate receptor

ORF :

Open-reading frames

PCP :

Phencyclidine

PPI :

Pre-pulse inhibition

SNP :

Single nucleotide polymorphism

ToM :

Theory of mind

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Acknowledgments

The experimental work about pLG72 was supported by a grant from Fondo di Ateneo per la Ricerca to SS and LP.

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Authors and Affiliations

  1. Dipartimento di Biotecnologie e Scienze della Vita, Università degli studi dell’Insubria, via J. H. Dunant 3, 21100, Varese, Italy

    Silvia Sacchi, Giorgio Binelli & Loredano Pollegioni

  2. The Protein Factory, Centro Interuniversitario di Biotecnologie Proteiche, Università degli studi dell′Insubria and Politecnico di Milano, Milano, Italy

    Silvia Sacchi & Loredano Pollegioni

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  1. Silvia Sacchi
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  2. Giorgio Binelli
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  3. Loredano Pollegioni
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Correspondence to Loredano Pollegioni.

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Sacchi, S., Binelli, G. & Pollegioni, L. G72 primate-specific gene: a still enigmatic element in psychiatric disorders. Cell. Mol. Life Sci. 73, 2029–2039 (2016). https://doi.org/10.1007/s00018-016-2165-6

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