基于全基因组重测序技术探索原发性高血压易感基因

发布时间：2018-02-26 06:23

本文关键词： 原发性高血压全基因组重测序基因组　出处：《中华高血压杂志》2017年08期 　论文类型：期刊论文

【摘要】：目的应用第二代测序技术结合DNA pooling策略和生物信息学分析技术寻找原发性高血压的易感基因。方法选择2014年6月至2015年6月深圳市人民医院心内科及重症医学院科门诊和住院的患者,以100例原发性高血压患者和100名健康人分别建立DNA pooling,应用第二代测序技术进行全基因组重测序。使用BWA软件对测序结果进行比对,分别对单核苷酸多态性(SNP)、插入缺失(InDel)、基因拷贝数变异(CNV)、单核苷酸变异(SNV)、结构变异(SV)等变异进行检测,应用ANNOVAR软件对所有的变异序列进行注释。针对检测到的基因变异位点数据,采用Fisher精确检验进行检验分析,检测达到统计学意义(P0.01)的位点即推测为与疾病相关的变异位点,然后利用公共数据库进行过滤,统计突变类型,并且将其在全基因组水平上进行分布分析,利用基因本体功能注释、京都基因和基因组百科全书(KEGG)通路分析、突变基因相互作用分析对筛选出的变异位点进行生物信息学检验,推测可能参与原发性高血压发病的易感基因。结果分组检验分析得到33 919个SNP位点、18 594个插入缺失位点、352个结构变异位点和88 707个CNV位点。纤维连接蛋白1(FN1)、蛋白激酶N1(PKN1)、融合蛋白19(CD19)、细胞分裂周期蛋白5样蛋白抗体(CDC5L)这4个位点是互相作用网络通路流经数据量最大的几个节点。结论通过全基因组重测序技术获得了全基因组水平上原发性高血压多种基因突变,而且发现尚未报道过的FN1、PKN1、CD19、CDC5L可能是原发性高血压发病过程中的关键节点基因。
[Abstract]:Objective to use the second generation sequencing technique, DNA pooling strategy and bioinformatics analysis technique to search for the susceptible genes of essential hypertension. Methods from June 2014 to June 2015, we selected the Department of Cardiology and the College of critical Medicine of Shenzhen people's Hospital. Outpatient and inpatient patients, DNA pooling was established in 100 patients with essential hypertension and 100 healthy persons. The whole genome was resequenced by the second generation sequencing technique. The sequencing results were compared by BWA software. Single nucleotide polymorphisms (SNPs), insertion deletions (InDell), copy number variation (CNV), single nucleotide mutation (SNPV), structural variation (SVV) were detected respectively. All the mutation sequences were annotated by ANNOVAR software. Fisher accurate test was used to test and analyze the loci that reached statistical significance (P0.01), that is to say, the mutation sites associated with disease were speculated, then filtered by common database, and the mutation types were counted. Distribution analysis was carried out on the whole genome level, and bioinformatics analysis of the selected mutation sites was carried out by means of gene Noumenon annotation, Kyoto gene and genome encyclopedia KEGG pathway analysis and mutation gene interaction analysis. Results 33,919 SNP loci, 18,594 insertion deletion sites, 352 structural variation sites and 88,707 CNV loci, fibronectin 1, FN1, protein were identified by cluster analysis. The four sites of kinase N1H PKN1, fusion protein 19s CD19 and cytokinin 5-like protein antibody CDC5L) are the nodes with the largest amount of data flowing through the interacting network pathway. Conclusion the whole genome can be obtained by whole genome re-sequencing technique. Multiple gene mutations in essential hypertension, It was also found that unreported FN1PKN1 CD19 CD19 CDC5L may be a key node gene in the pathogenesis of essential hypertension.
【作者单位】：深圳市龙岗区人民医院重症医学科;暨南大学第二临床医学院深圳市人民医院重症医学科临床医学研究中心;
【基金】：广东省科技厅项目(2014A020212702)
【分类号】：R544.11

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