重性抑郁障碍长链非编码RNA的筛选及初步分析

发布时间：2018-04-30 14:50

  本文选题：重性抑郁障碍 + 长链非编码RNA　； 参考：《山西医科大学》2013年硕士论文

【摘要】：目的 1.建立重性抑郁障碍外周血白细胞中差异LncRNA/mRNA共表达网络； 2.应用生物学与信息学手段，筛选抑郁障碍差异表达的LncRNA并进行初步分析。 方法 采用病例-对照研究，严格按照入排标准，收集病例组和对照组各10例，控制性别、年龄等因素后，对病例组和对照组进行一一配对，采用DSM--IV轴I障碍定式临床检查（SCID-I/P)对重性抑郁障碍患者进行筛查诊断，应用汉密尔顿抑郁量表(HAMD)进行临床症状的评定,要求病例组符合HAMD21分（17项）或35分（24项）。提取外周血总RNA，应用微阵列技术使用Arrystar公司LncRNA芯片（可同时检测LncRNA/mRNA），检测外周血白细胞中的LncRNA、mRNA并进行聚类分析,比较病例组和对照组LncRNA差异表达的情况，并建立LncRNA/mRNA的共表达网络；其次，查阅文献报道抑郁障碍密切相关的mRNA以及上述方法检测出的差异表达mRNA，结合芯片筛选出的LncRNA，按照特定基因表达标准化信号强度，筛选出差异表达中起核心调控作用的LncRNA。使用NimbleScan software (version2.5）对原始数据进行预处理后，采用SPSS17.0软件包进行统计分析，在实验组、对照组先控制性别年龄，采用随机方差模型（Random variance model，RVM）校正后进行两分类差异基因筛选(Two classification difference genetic screening，TwoclassDif），采用t检验方法，得到显著差异表达的mRNA和LncRNA；对筛选到的差异mRNA和LncRNA进行共表达（co-expression）分析，以P0.05为差异有统计学意义，筛选出在共表达网络中起核心调控作用的LncRNA，并对其进行初步分析。 结果 1.重性抑郁障碍患者外周血白细胞长链非编码RNA与对照组相比，差别具有统计学意义（P＜0.05），共筛选出2795条差异表达mRNAs；960条差异表达的LncRNAs，其中729条表达上调、231条表达下调，据此构建重性抑郁障碍外周血白细胞中差异LncRNA/mRNA共表达网络。 2.重性抑郁障碍患者外周血白细胞中chr1:29493450-29493605chr1:76255317-76255564chr3:47048304-47048512chr5:134693047-134693150chr10:27802593-27802714chr10:103554357-103554675chr11:64534866-64535009chr14:21698593-21698781chrX:108927695-108927824chr20:25670953-25671104chr13113570824-113570935等11条LncRNA的表达，，差别具有统计学意义（P＜0.05）。 结论 1.重性抑郁障碍患者外周血LncRNA存在差异表达； 2.11条差异表达的LncRNA可能与抑郁障碍相关。
[Abstract]:Purpose 1. To establish the differential LncRNA/mRNA coexpression network in peripheral blood leukocytes of patients with severe depressive disorder. 2. LncRNA differentially expressed in depressive disorder was screened and analyzed by biological and informatics methods. Method A case-control study was used to collect 10 cases each from the case group and the control group in strict accordance with the admission criteria. After controlling for gender and age, the case group and the control group were matched one by one. SCID-I / P) was used to screen and diagnose the patients with severe depressive disorder, and the clinical symptoms were evaluated by Hamilton Depression scale (Hamd). The patients were required to meet the HAMD21 score of 17 items or 35 points to 24 items. Total RNAs in peripheral blood were extracted, and microarray technique was used to detect LncRNA-mRNA-mRNAs (LncRNA-mRNA-mRNAs) in peripheral blood leukocytes, and cluster analysis was carried out to compare the differential expression of LncRNA between the case group and the control group, and to establish the coexpression network of LncRNA/mRNA. Secondly, the mRNA closely related to depression disorder and the differential expression mRNAs detected by the above methods were reviewed. Combined with the LncRNAs screened by the microarray, the LncRNAs which played a central role in the differential expression were screened according to the standardized signal intensity of the specific gene expression. NimbleScan software version 2.5) was used to preprocess the original data, and SPSS17.0 software package was used for statistical analysis. In the experimental group and the control group, the sex and age were controlled first. Random variance model (RVM) was used to screen two classification difference genetic screening genes for two class difons. T test was used to obtain mRNA and LncRNAs that were significantly differentially expressed, and coexpression of mRNA and LncRNA were analyzed. The LncRNAs which play a central role in the coexpression network were screened and analyzed. Result 1. Compared with the control group, the long chain non-coding RNA of peripheral blood leukocytes in patients with severe depressive disorder showed significant difference (P < 0.05). A total of 2795 LncRNASs expressing mRNAs-960 differentially expressed LncRNASS were screened out, and 729 of them up-regulated the expression of mRNAs-960, and down-regulated the expression of LncRNASs. Based on this, the differential LncRNA/mRNA coexpression network in peripheral blood leukocytes of patients with severe depressive disorder was constructed. 2. 閲嶆

本文编号：1824988