圆锥动脉干畸形患儿NOTCH1和JAG1基因3’非编码区变异分析  

Analysis of variants located in 3'UTR regions of NOTCH1 and JAG1 genes for children with conotruncal heart defects

作　　者：徐丽娟[1] 刘惠东[1] 徐让[2] 李奋[3] 陈笋[1] XU Li-juan;LIU Hui-dong;XU Rang;LI Fen;CHEN Sun(Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China;Scientific Research Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China;Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China)

机构地区：[1]上海交通大学医学院附属新华医院小儿心血管科,上海200092 [2]上海交通大学医学院附属新华医院科研中心,上海200092 [3]上海交通大学医学院附属上海儿童医学中心,上海200127

出　　处：《上海交通大学学报（医学版）》2017年第2期184-189,共6页Journal of Shanghai Jiao tong University:Medical Science

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)~~

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P<0.05)。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。To explore the correlation between variants located in 3’ untranslated regions (3’UTR) of NOTCH1 and JAG1 genes and conotruncal heart defects (CTD). Methods · Six hundred CTD children without 22q11 deletion and three hundred healthy children were enrolled in this hospital-based case-control study. Variants located in the 3'UTR regions of NOTCH1 and JAG1 genes were detected by high-throughput sequencing.The accuracy of the variants were verified by PCR and Sanger sequencing. Online software PicTar, TargetScan and microRNA.org were used to make functional predictions. Results · One mutation and three SNPs were found in the 3 ’UTR of NOTCH1. Three mutations and six SNPs were found in the3’UTR of JAG1. The genotypic distributions of two SNPs (rs3840074 and rs8708) located in JAG1 3’UTR between CTD group and the controls were statistically significant (both P<0.05). Results of prediction showed that all the four mutations and two meaningful SNPs could bind to microRNA.Conclusion · The variants located in 3’UTR regions of NOTCH1 and JAG1 genes may be related to the occurrence of CTD.

关 键 词：圆锥动脉干畸形 NOTCH1基因 JAG1基因 3’非编码区 微小RNA 单核苷酸多态性 

分 类 号：R725.4[医药卫生—儿科]