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Comparative analysis of MBD-seq and MeDIP-seq and estimation of gene expression changes in a rodent model of schizophrenia

机译:MBD-SEQ与MEDIP-SEQ的比较分析及精神分裂症啮齿动物模型中基因表达变化的估算

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We conducted a comparative study of multiplexed affinity enrichment sequence methodologies (MBD-seq and MeDIP-seq) in a rodent model of schizophrenia, induced by in utero methylazoxymethanol acetate (MAM) exposure. We also examined related gene expression changes using a pooled sample approach. MBD-seq and MeDIP-seq identified 769 and 1771 differentially methylated regions (DMRs) between F2 offspring of MAM-exposed rats and saline control rats, respectively. The assays showed good concordance, with similar to 56% of MBD-seq-detected DMRs being identified by or proximal to MeDIP-seq DMRs. There was no significant overlap between DMRs and differentially expressed genes, suggesting that DNA methylation regulatory effects may act upon more distal genes, or are too subtle to detect using our approach. Methylation and gene expression gene ontology enrichment analyses identified biological processes important to schizophrenia pathophysiology, including neuron differentiation, prepulse inhibition, amphetamine response, and glutamatergic synaptic transmission regulation, reinforcing the utility of the MAM rodent model for schizophrenia research. (C) 2017 Elsevier Inc. All rights reserved.
机译:我们在精神分裂症的啮齿动物模型中进行了对复用亲和富集序列方法(MBD-SEQ和MEDIP-SEQ)的比较研究,所述精神分裂症模型中由Uttero甲基氧酰甲醇乙酸甲醇(MAM)曝光诱导。我们还使用汇集的样品方法检查相关的基因表达变化。 MBD-SEQ和MEDIP-SEQ分别鉴定了MAM暴露大鼠和盐水对照大鼠的F2后代之间的769和1771次差异甲基化区域(DMR)。该测定显示出良好的一致性,类似于MBD-SEQ检测到的56%的MBD-SEQ检测到的DMRS或近似到MEDIP-SEQ DMRS。 DMRS和差异表达基因之间没有显着重叠,表明DNA甲基化调节效应可以在更远侧基因上起作用,或者太微妙地检测使用我们的方法。甲基化和基因表达基因本体学院浓缩分析鉴定了对精神分裂症病理学生理学重要的生物学过程,包括神经元分化,预筛选,安非他明反应和谷氨酸突突触突触传输​​调节,加强了母羊啮齿动物模型对精神分裂症研究的效用。 (c)2017年Elsevier Inc.保留所有权利。

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