2009
DOI: 10.1038/mp.2009.53
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Association of common copy number variants at the glutathione S-transferase genes and rare novel genomic changes with schizophrenia

Abstract: Copy number variants (CNVs) are a substantial source of human genetic diversity, influencing the variable susceptibility to multifactorial disorders. Schizophrenia is a complex illness thought to be caused by a number of genetic and environmental effects, few of which have been clearly defined. Recent reports have found several low prevalent CNVs associated with the disease. We have used a multiplex ligation-dependent probe amplification-based (MLPA) method to target 140 previously reported and putatively rele… Show more

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Cited by 79 publications
(52 citation statements)
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References 67 publications
(88 reference statements)
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“…All MLPA reactions were analyzed on an ABI PRISM 3100 Genetic analyzer according to manufacturers' instructions. Each MLPA signal was normalized and compared to the corresponding peak height obtained in control samples [57]. The MLPA assay was also used to analyze the frequency of the CNVs identified in the entire cohort (480 subjects) and in the control population (480 individuals).…”
Section: Methodsmentioning
confidence: 99%
“…All MLPA reactions were analyzed on an ABI PRISM 3100 Genetic analyzer according to manufacturers' instructions. Each MLPA signal was normalized and compared to the corresponding peak height obtained in control samples [57]. The MLPA assay was also used to analyze the frequency of the CNVs identified in the entire cohort (480 subjects) and in the control population (480 individuals).…”
Section: Methodsmentioning
confidence: 99%
“…Polymorphisms and copy number variations in genes related to the GSH synthesis and metabolism are associated with schizophrenia. 50, 69, 70, 71, 72, 73, 74, 75 Moreover, subjects with high-risk genotype of the key GSH synthesizing gene GCLC presents low prefrontal GSH levels. 76 Mice with a functional deletion of the modulatory subunit (GCLM) of the key GSH synthesizing enzyme constitute a model of redox dysregulation with 60–70% decreased brain GSH levels.…”
Section: Oxidative Stress and Pvi Integrity In Preclinical Models Of mentioning
confidence: 99%
“…Genetic risk factors combined with environmental insults can affect the homeostasis of one or several of the “hub” systems which in turn could impact the others through reciprocal interactions ( reciprocal arrows ). Genetic vulnerability to redox dysregulation in schizophrenia is supported by polymorphisms and copy number variations in genes related to the GSH metabolism (Gravina et al, 2011; Gysin et al, 2007; Mehta et al, 2013; Rodriguez-Santiago et al, 2010; Tosic et al, 2006). In addition, impaired function of proteins coded by other plausible risk genes, including DISC1, PROD, G72, NRG, DTNBP1 , indirectly leads to oxidative stress often via mitochondrial dysfunction (Clay et al, 2011; Gokhale et al, 2012; Goldshmit et al, 2001; Johnson et al, 2013; Krishnan et al, 2008; Park et al, 2010).…”
Section: Figmentioning
confidence: 99%