羊水游离RNA中心脏发育共表达关键基因分析  

Analysis of co-expressed hub genes of heart development in free RNA from amniotic fluid

作　　者：杨树法[1] 秦朗 刘妍[1] 刘欣[2] 闫有圣 司艳梅[1] YANG Shufa;QIN Lang;LIU Yan;LIU Xin;YAN Yousheng;SI Yanmei(Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing Maternal and Child Health Care Hospital,Beijing 100026,China;Department of Genetics&Developmental Biology,Capital Medical University School of Basic Medical Sciences,Beijing 100069,China)

机构地区：[1]首都医科大学附属北京妇产医院/北京妇幼保健院,北京100026 [2]首都医科大学基础医学院医学遗传学与发育生物学系,北京100069

出　　处：《中国优生与遗传杂志》2021年第10期1416-1421,共6页Chinese Journal of Birth Health & Heredity

基　　金：北京市教育委员会科技计划项目(KM201910025027)。

摘　　要：目的筛选孕中期羊水游离RNA转录组中心脏发育相关的共表达关键基因。方法以正常孕妇羊水游离RNA的芯片检测结果为基础,利用加权基因共表达网络分析,建立共表达网络模块。在心脏中表达量高于机体平均表达量10倍的基因作为心脏特异性基因,通过对各共表达模块中的基因进行筛选,建立心脏特异的共表达模块。对心脏特异性共表达模块中的基因进行GO分析,探究各个共表达模块的功能。利用基因间相互作用和基因在羊水游离RNA中的表达量筛选心脏特性共表达模块中的关键基因。结果研究中利用加权基因共表达网络分析共建立16个共表达模块,在Human Protein Atlas数据库中筛选到159个心脏特异性基因。在blue、brown、green及turquoise心脏特异性模块中富集到心肌细胞分化、心脏形态发育、心肌组织发育、心脏传导、心脏收缩、心脏收缩调节、心率调节及心肌纤维组装等过程相关的基因属性分类。通过分析基因间相互作用及基因在孕中期的平均表达量发现,blue模块(TNNC1、FABP3、TNNI3、MYOM3及BMP10)、brown模块(MYL4、NPPA、NPPB、GJA3、HRC、DHRS7C及HSPB3)、green模块(MYH7、MYH7B及NKX2-5)及turquoise模块(POPDC2、NEBL、CDH2、TCAP、MYL7、TPM1、XIRP1、HCN4、CASQ2及KCNA5)共25个关键基因。结论本研究获得了心脏发育密切相关且具有共表达关系的关键基因,可作为潜在的产前诊断中监测心脏发育的标志物。Objective Co-expressed hub genes of heart development in free RNA transcriptome from amniotic fluid cell free RNA transcriptomeassociated during second trimester were screened.Methods Based on amniotic fluid cell free RNA transcriptome in normal trimester pregnancy,gene co-expressed modules were established via weighted gene co-expression network analysis.Specific heart genes were defined as genes with expression values in heart 10 times higher than mean expression value in all tissues.Specific heart co-expression modules were constructed via intersection of genes in co-expressed network modules and specific genes in heart tissue.GO analyze were used to explain biological functions of specific heart co-expression modules.Hub genes from specific heart co-expression modules were filtered through employing protein-protein interaction analysis and gene expression values of free RNA transcriptome in amniotic fluid.Results A total of 16 co-expression modules were set up via weighted gene co-expression network analysis.In addition,159 specific genes in heart tissue were detected in Human Protein Atlas database.Functions of blue,brown,green and turquoise module were in close relation with cardiac muscle cell differentiation,heart morphogenesis,cardiac muscle tissue development,cardiac conduction,cardiac muscle contraction,regulation of heart contraction,regulation of heart rate and myofibril assembly.A total of 25 hub genes were detected in blue module(TNNC1,FABP3,TNNI3,MYOM3 and BMP10),brown module(MYL4,NPPA,NPPB,GJA3,HRC,DHRS7C and HSPB3),green module(MYH7,MYH7B and NKX2-5)and turquoise module(POPDC2,NEBL,CDH2,TCAP,MYL7,TPM1,XIRP1,HCN4,CASQ2 and KCNA5)via gene-gene interactions and gene expression in amniotic fluid cell free RNA transcriptome.Conclusion Co-expressed hub genes derived from heart development during second trimester are screened in our study and could be served as prognostic markers for monitoring fetal heart development.

关 键 词：羊水游离RNA 产前诊断 心脏发育 诊断标志物 基因共表达网络 

分 类 号：R714.5[医药卫生—妇产科学]