原发性帕金森病诊断、治疗的靶基因筛选

发布时间：2018-07-03 05:07

本文选题：原发性帕金森病 + 靶基因筛选　；参考：《山东医药》2017年24期

【摘要】：目的筛选原发性帕金森病(PD)诊断、治疗的靶基因。方法在基因表达综合(GEO)数据库中以"帕金森(Parkinson)"作为关键词,组织类型限定为中脑黑质,数据类型限定为基于基因芯片检测的基因表达谱数据,筛选出1个符合条件的数据集(GSE7621),该芯片数据包含9个正常(中脑无病变)样本(正常组)和16个原发性PD样本(PD组)。利用R编程语言的相关工具包对原始芯片数据进行预处理和差异表达基因的筛选。利用DAVID数据库对差异表达基因进行功能注释,并且构建差异表达基因的差异共表达网络及转录调控网络。将PC12细胞分为两组,分别为对照组和观察组,对照组常规培养,观察组给予50μmol/L 1-甲基-4-苯基吡啶离子(MPP)处理;处理24 h时,采用实时荧光定量PCR(qRT-PCR)法检测差异表达基因的相对表达量。结果正常组及PD组存在396个差异表达基因,相对于正常组,PD组存在下调基因229个、上调基因167个,主要富集功能为突触活动、多巴胺(DA)合成、神经元活动、突触传递、神经元投射、儿茶酚胺生物合成等。两组表达差异性最大的前十位基因分别为Zcchc6、Socs7、Ythdc1、Taf5、Spata13、Slc5a3、Heca、Epc2、Ddx23、Cdk2ap2。调控差异表达基因较多的前十个转录因子(TF)分别为AHR、DAND5、PSG1、SP1、PAX5、ARNT、MIA3、AP-2gamma、CREB1、AP-2alpha A。qRT-PCR结果显示,观察组与对照组Zcchc6、Socs7、Spata13、Slc5a3、Epc2、Cdk2ap2 mRNA表达量比较,P0.05或0.01;两组Ythdc1、Taf5、Heca、Ddx23 mRNA表达量比较P均0.05。结论 Zcchc6、Socs7、Spata13、Slc5a3、Epc2、Cdk2ap2基因可能与原发性PD的发生、发展相关,可能作为其诊断及治疗的靶基因。
[Abstract]:Objective to screen target genes for diagnosis and treatment of primary Parkinson's disease (PD). Methods in the gene expression synthesis (GEO) database, "Parkinson" was used as the key word, the tissue type was limited to the substantia nigra, and the data type was defined as the gene expression profile data based on gene chip detection. One eligible data set (GSE7621) was screened. The chip data contained 9 normal subjects (normal group) and 16 primary PD samples (PD group). The relative toolkits of R programming language are used to preprocess the original chip data and screen differentially expressed genes. Using DAVID database to annotate differentially expressed genes and construct differential coexpression networks and transcriptional regulatory networks of differentially expressed genes. PC12 cells were divided into two groups: control group and observation group. The control group was treated with 50 渭 mol / L 1-methyl-4-phenylpyridine ion (MPP) for 24 h. The relative expression of differentially expressed genes was detected by real-time fluorescent quantitative PCR (qRT-PCR). Results there were 396 differentially expressed genes in normal group and PD group. Compared with normal group, there were 229 down-regulated genes and 167 up-regulated genes in PD group. The main enrichment functions were synaptic activity, dopamine (DA) synthesis, neuronal activity and synaptic transmission. Neuronal projections, catecholamine biosynthesis and so on. The top ten genes of the two groups were Zcchc6G, Socs7 Ythdc1, Taf5, Spata13, Slc5a3, Heca, Epc2Ddx23, Cdk2ap2, respectively. The first ten transcriptional factors (TF) with more differentially expressed genes were AHR-DAND5, PSG1, PAX5, ARNTN, MIA3AP-2gamma-CREB1AP-2alpha A.qRT-PCR, respectively. The results of RT-PCR showed that the expression of Zcchc6Socs7Sa13patc5a3A3Epc2CDk2ap2 mRNA was significantly higher than that of control group (P0.05 or 0.01), and that of Ythdc1Taf5Heca5 / Ddx23 was higher than that of control group (P 0.05). Conclusion the Spata13Spata13Slc5a3A3 Epc2CDk2ap2 gene may be associated with the occurrence and development of primary PD, and may be used as a target gene for diagnosis and treatment.
【作者单位】：天津市海河医院;天津市环湖医院;天津医科大学总医院;
【分类号】：R742.5

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