圆锥动脉干畸形患儿NOTCH1和JAG1基因3’非编码区变异分析

发布时间：2018-08-14 14:20

【摘要】：目的·探索NOTCH1和JAG1的3’非编码区(3’UTR)核苷酸变异与心脏圆锥动脉干畸形(CTD)的相关性。方法·采用病例-对照的研究方法,收集600名无22q11缺失的CTD患儿以及300名正常对照儿童。应用高通量测序技术直接检测样本人群NOTCH1和JAG1 3’UTR区段的序列,筛选变异位点,通过PCR和Sanger测序法验证变异的准确性。运用在线软件Target Scan、Pic Tar和micro RNA.org对变异位点进行功能预测分析。结果·检测出CTD患儿NOTCH1 3’UTR区存在1个新发突变和3个单核苷酸多态性(SNP),JAG1 3’UTR区存在3个新发突变和6个SNP位点。其中JAG1 3’UTR区有2个SNP位点(rs3840074、rs8708)的基因型在病例组和对照组间的分布差异有统计学意义(均P0.05)。预测结果显示4个突变位点及2个有差异的SNP位点均可与微小RNA结合。结论·NOTCH1和JAG1 3’UTR区的核苷酸变异可能与心脏圆锥动脉干畸形的发生相关。
[Abstract]:Objective to investigate the correlation between 3 'noncoding region (3'UTR) nucleotide variation in NOTCH1 and JAG1 and (CTD) in cardiac conical trunk malformation. Methods A case-control study was conducted in 600 children with CTD without 22q11 deletion and 300 normal controls. The high throughput sequencing technique was used to detect the sequence of NOTCH1 and JAG1 3'UTR directly and to screen the mutation sites. The accuracy of the variation was verified by PCR and Sanger sequencing. The functional prediction of mutation sites was carried out by using online software Target sic Tar and micro RNA.org. Results one new mutation in the NOTCH1 3'UTR region and three single nucleotide polymorphisms in the JAG1 3'UTR region of (SNP) were detected in children with CTD. There were 3 new mutations and 6 SNP loci in the NOTCH1 3'UTR region. The genotypes of two SNP loci (rs3840074, rs8708) in the JAG1 3'UTR region were significantly different between the case group and the control group (P0.05). The predicted results showed that four mutation sites and two different SNP loci could bind to small RNA. Conclusion the nucleotide variation of NOTCH1 and JAG1 3'UTR may be related to the malformation of cardiac conical artery trunk.
【作者单位】：上海交通大学医学院附属新华医院小儿心血管科;上海交通大学医学院附属新华医院科研中心;上海交通大学医学院附属上海儿童医学中心;
【基金】：上海市公共卫生体系建设三年行动计划(GWIV-23) 上海市教育委员会科研创新项目(15ZZ055)~~
【分类号】：R725.4

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