Supportive Evidence for Reduced Expression of GNB1L in Schizophrenia

Ishiguro, Hiroki; Koga, Minoru; Horiuchi, Yasue; Noguchi, Emiko; Morikawa, Miyuki; Suzuki, Yoshimi; Arai, Makoto; Niizato, Kazuhiro; Iritani, Shyuji; Itokawa, Masanari; Inada, Toshiya; Iwata, Nakao; Ozaki, Norio; Ujike, Hiroshi; Sasaki, Tsukasa; Takahashi, Makoto; Watanabe, Yuichiro; Someya, Toshiyuki; Kakita, Akiyoshi; Takahashi, Hitoshi; Nawa, Hiroyuki; Arinami, Tadao

doi:10.1093/schbul/sbn160

Cited by 26 publications

(17 citation statements)

References 36 publications

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“…156–162 Although not many studies are available, reports to date regarding association of GNB1L SNPs with schizophrenia have all been positive. 163–165 Comprehensive screenings of SNPs on 22q11.2 in individuals without 22q11.2 hemizygosity have identified association of SNPs on DGCR6, PRODH, ZDHHC8 ( KIAA1292 ) and RTN4R ( NOGO-R ) with schizophrenia and childhood-onset schizophrenia. 162,166 However, none of these common variants was found to be associated with schizophrenia 4,167 or ASD 3,168,169 in recent large-scale genome-wide association studies, confirming that SNPs on 22q11.2 genes are unlikely to contribute to risk for schizophrenia or ASD.…”

Section: Identifying Specific Genes Within 22q112 Cnvmentioning

confidence: 99%

Copy number variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders

et al. 2013

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Recently discovered genome-wide rare copy number variants (CNVs) have unprecedented levels of statistical association with many developmental neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, intellectual disability and attention deficit hyperactivity disorder. However, as CNVs often include multiple genes, causal genes responsible for CNV-associated diagnoses and traits are still poorly understood. Mouse models of CNVs are in use to delve into the precise mechanisms through which CNVs contribute to disorders and associated traits. Based on human and mouse model studies on rare CNVs within human chromosome 22q11.2, we propose that alterations of a distinct set of multiple, noncontiguous genes encoded in this chromosomal region, in concert with modulatory impacts of genetic background and environmental factors, variably shift the probabilities of phenotypes along a predetermined developmental trajectory. This model can be further extended to the study of other CNVs and may serve as a guide to help characterize the impact of genes in developmental neuropsychiatric disorders.

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Section: Identifying Specific Genes Within 22q112 Cnvmentioning

confidence: 99%

Copy number variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders

et al. 2013

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“…Other CNV-driven genes include TBX1 and GNB1L, both overlapping the 22q11.2 deletion, which have been associated with neuropsychiatric disorders such as schizophrenia and autism (Chen et al 2012; Ishiguro et al 2010; Hiramoto et al 2011). …”

Section: A Systems Biology Approach For Rare and Singleton Cnvsmentioning

confidence: 99%

Copy number variability in Parkinson’s disease: assembling the puzzle through a systems biology approach

et al. 2016

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Parkinson’s disease (PD), the second most common progressive neurodegenerative disorder of aging, was long believed to be a non-genetic sporadic origin syndrome. The proof that several genetic loci are responsible for rare Mendelian forms has represented a revolutionary breakthrough, enabling to reveal molecular mechanisms underlying this debilitating still incurable condition. While single nucleotide polymorphisms (SNPs) and small indels constitute the most commonly investigated DNA variations accounting for only a limited number of PD cases, larger genomic molecular rearrangements have emerged as significant PD-causing mutations, including submicroscopic Copy Number Variations (CNVs). CNVs constitute a prevalent source of genomic variations and substantially participate in each individual’s genomic makeup and phenotypic outcome. However, the majority of genetic studies have focused their attention on single candidate-gene mutations or on common variants reaching a significant statistical level of acceptance. This gene-centric approach is insufficient to uncover the genetic background of polygenic multifactorial disorders like PD, and potentially masks rare individual CNVs that all together might contribute to disease development or progression. In this review, we will discuss literature and bioinformatic data describing the involvement of CNVs on PD pathobiology. We will analyze the most frequent copy number changes in familiar PD genes and provide a “systems biology” overview of rare individual rearrangements that could functionally act on commonly deregulated molecular pathways. Assessing the global genome-wide burden of CNVs in PD patients may reveal new disease-related molecular mechanisms, and open the window to a new possible genetic scenario in the unsolved PD puzzle.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-016-1749-4) contains supplementary material, which is available to authorized users.

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“…Details of the condition of the postmortem brains have been provided elsewhere. 23,24 Analysis of DPP6 transcription in human brain tissue Total RNA was extracted from human brain tissues by using the ISOGEN Reagent (Nippon Gene Co., Tokyo, Japan). The RNA quality was checked by using a Nanodrop ND-1000 spectrophotometer (LMS, Tokyo, Japan) to yield an optical density (OD) 260/280 ratio of 1.8-2 and an OD 260/230 of 1.8 or greater.…”

Section: Genotyping and Statisticsmentioning

confidence: 99%

DPP6 as a candidate gene for neuroleptic-induced tardive dyskinesia

et al. 2011

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We implemented a two-step approach to detect potential predictor gene variants for neuroleptic-induced tardive dyskinesia (TD) in schizophrenic subjects. First, we screened associations by using a genome-wide (Illumina HumanHapCNV370) SNP array in 61 Japanese schizophrenia patients with treatment-resistant TD and 61 Japanese schizophrenia patients without TD. Next, we performed a replication analysis in 36 treatment-resistant TD and 138 non-TD subjects. An association of an SNP in the DPP6 (dipeptidyl peptidase-like protein-6) gene, rs6977820, the most promising association identified by the screen, was significant in the replication sample (allelic P=0.008 in the replication sample, allelic P=4.6 × 10(-6), odds ratio 2.32 in the combined sample). The SNP is located in intron-1 of the DPP6 gene and the risk allele was associated with decreased DPP6 gene expression in the human postmortem prefrontal cortex. Chronic administration of haloperidol increased Dpp6 expression in mouse brains. DPP6 is an auxiliary subunit of Kv4 and regulates the properties of Kv4, which regulates the activity of dopaminergic neurons. The findings of this study indicate that an altered response of Kv4/DPP6 to long-term neuroleptic administration is involved in neuroleptic-induced TD.

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Supportive Evidence for Reduced Expression of GNB1L in Schizophrenia

Cited by 26 publications

References 36 publications

Copy number variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders

Copy number variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders

Copy number variability in Parkinson’s disease: assembling the puzzle through a systems biology approach

DPP6 as a candidate gene for neuroleptic-induced tardive dyskinesia

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