基于GWAS数据的阿尔兹海默病相关miRNA的识别研究

发布时间：2019-01-05 11:55

【摘要】：阿尔兹海默病(Alzheimer’s disease,AD)是一种神经退行性疾病。目前,大部分AD的风险因子尚未被发现。miRNA作为一类转录后调控因子,可以依靠其序列的特异性来识别目标基因并发挥功能,对基因的表达调控起着十分关键的作用。越来越多的证据表明miRNA可以影响神经疾病的形成与发展,并且已有研究显示miRNA与AD的发病风险相关。在本研究中,我们应用了一个系统的研究方法对AD潜在的miRNA风险因子进行了识别。在第一阶段,我们使用大样本的AD全基因组关联分析数据对miRNA进行了初步识别与分析,并成功得到6条候选的AD相关miRNA。在第二阶段,我们利用AD病人及正常人的大脑组织的RNA-seq数据对6条候选miRNA进行了差异表达分析,发现在6条候选miRNA中,miR-218-5p在病人大脑组织中表现出显著的上调。在第三阶段,我们预测了miR-218-5p的靶基因并对靶基因进行了差异表达分析,结果发现miR-218-5p的多个靶基因在AD病人大脑组织中存在显著的异常表达。在第四阶段,我们对miR-218-5p的靶基因进行了功能和通路富集分析,结果显示miR-218-5p的靶基因显著的富集在多条神经相关通路上。综上,我们的结果揭示了miR-218-5p有可能是神经系统中的一个关键调控因子并且与阿尔兹海默病的发病风险相关,这些结果可以为miR-218-5p的基因表达调控研究以及阿尔兹海默病分子调控网络的探索提供重要的信息。
[Abstract]:Alzheimer's disease (Alzheimer's disease,AD) is a neurodegenerative disease. At present, most of the risk factors of AD have not been found. As a kind of posttranscriptional regulation factors, miRNA can recognize target gene and function by its sequence specificity, which plays a key role in gene expression regulation. There is growing evidence that miRNA can affect the formation and development of neurological diseases, and studies have shown that miRNA is associated with the risk of AD. In this study, we applied a systematic method to identify the potential miRNA risk factors of AD. In the first stage, we identified and analyzed the miRNA using a large sample of AD genomic association analysis data, and obtained six candidate AD related miRNA. successfully. In the second stage, we analyzed the differential expression of 6 candidate miRNA using RNA-seq data of AD patients and normal subjects. We found that miR-218-5p was significantly up-regulated in the brain tissues of patients with AD. In the third stage, we predicted the target gene of miR-218-5p and analyzed the differential expression of the target gene. The results showed that there was significant abnormal expression of multiple target genes of miR-218-5p in the brain tissue of AD patients. In the fourth stage, we analyzed the function and pathway enrichment of the target genes of miR-218-5p. The results showed that the target genes of miR-218-5p were significantly enriched in several nerve related pathways. Taken together, our results suggest that miR-218-5p may be a key regulator of the nervous system and be associated with the risk of Alzheimer's disease. These results may provide important information for the study of gene expression regulation of miR-218-5p and the exploration of molecular regulatory networks for Alzheimer's disease.
【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.16

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