Increased Variability of Genomic Transcription in Schizophrenia.
Increased Variability of Genomic Transcription in Schizophrenia.
复制标题
精神分裂症基因组转录变异性增加
DOI：
10.1038/srep17995
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发表时间：
2015-12-10
影响因子：
4.6
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Zhang F;Yao Shugart Y;Yue W;Cheng Z;Wang G;Zhou Z;Jin C;Yuan J;Liu S;Xu Y
精神分裂症(SZ)是一种遗传性很高的严重慢性精神障碍。目前的微阵列分析通常侧重于识别与表型相关的差异表达基因或丰富的途径。在疾病中是否存在基因组转录的变异性变化还很少被探索。在这项研究中，我们比较了早发性SZ(EOS)患者基因组转录的变异系数(CV，标准差与平均值的比率)，以及血液mRNA微阵列数据集和血液微RNA(MiRNA)微阵列数据集中的对照组。此外，我们用实时定量聚合酶链式反应(RT-qPCR)分析比较了30例患者治疗12周前后血液中17个基因表达水平的变异系数。我们的结果表明，无论是在mRNA数据集还是在miRNA数据集上，患者组的基因组转录变异系数都显著高于对照组。30例患者治疗后基因表达变异系数较治疗前明显降低。我们的研究可能涉及SZ患者血液基因表达的变异性，为SZ患者外周血转录组的异常提供进一步的证据。鉴于外周血可以很容易地从患者身上采集并进行纵向追踪，我们的结果可能表明一种新的方法，有助于识别临床亚型的特征、他们的预后和治疗反应。
Schizophrenia (SZ) is a severe chronic mental disorder with a high heritability. Current microarray analyses typically focus on identifying differentially expressed genes or enriched pathways relevant to phenotypes. Whether there is a variability change of the genomic transcription in diseases has rarely been explored. In this study, we compared coefficient of variation (CV, the ratio of the standard deviation to the mean) of genome transcription of early-onset SZ (EOS) patients with controls in a blood mRNA microarray dataset and a blood microRNA (miRNA) microarray dataset. Furthermore, we compared CV of the expression levels of 17 genes in blood of the 30 patients before and after the 12-week treatment using real-time quantitative PCR (RT-qPCR) analysis. Our results indicated a significant increase of CV of genome transcription in patients compared with controls in both the mRNA and the miRNA datasets. The 30 after-treatment patients showed a significant decrease of CV of gene expression compared with the before-treatment patients. Our study may implicate the blood gene expression variability in SZ, providing further evidence supporting the abnormality of peripheral blood transcriptome in SZ. Given that peripheral blood can be easily collected from patients and followed longitudinally, our results may indicate a new way to facilitate the identification of the signatures of clinical subtypes, their prognosis and treatment response.