摘要
目的探讨神经管缺陷(neural tube defects,NTDs)家系中DNA甲基化的特点以及差异性甲基化基因的相关通路。方法收集3个NTDs家系12例研究对象,以NTDs患者作为病例组,家系中表型正常的成员作为对照组。抽取12例研究对象的外周血,提取基因组DNA,进行DNA甲基化检测。家系中患者-非患者(主要以亲-子为主)进行配对分析,并检测差异性甲基化基因与NTDs是否存在共分离关系。应用DAVID软件分析差异甲基化基因所在通路。结果通过甲基化位点的配对分析发现VTRNA2-1基因是唯一一个所包含的CpG位点均发生甲基化改变的基因,且该基因甲基化与NTDs家系存在共分离关系。高甲基化基因所在通路包括:细胞膜组份、细胞蛋白代谢调控、肌动蛋白细胞骨架调控等,低甲基化基因所在通路包括:转录调节因子活性、细胞粘附、神经元分化等。结论VTRNA2-1基因甲基化与NTDs家系存在共分离关系,差异甲基化基因所在通路可能涉及神经管发育相关机制。
Objective To explore the characteristics of differentially methylated genes and gene ontology associated with neural tube defects (NTDs). Methods Twelve subjects from 3 NTDs pedigrees were enrolled. Patients with NTDs have served as the case group, while their family members with normal phenotypes have served as the control group. Genomic DNA was extracted from peripheral venous blood samples of the families and used for DNA methylation analysis. Pairwise comparison was carried out primarily for patient-offspring pairs, and co-segregation of methylation pattern with NTDs was analyzed. Pathway related to differentially methylated genes was predicted with DAVID software. Results Pairwise comparison indicated that VTRNA2-1 was the only gene in which all CpG sites were methylated. Co-segregation of VTRNA2-1 gene methylation with NTDs was found in all pedigrees. Pathways of hypermethylated genes included plasma membrane component, regulation of cellular protein metabolic process, and regulation of actin cytoskeleton organization, while the pathways of hypomethylated genes have included transcription regulator activity, cell adhesion, and neuronal differentiation. Conclusion Methylation of the VTRNA2-1 gene has co-segregated with NTDs in the studied pedigrees. The pathways of differentially methylated genes has involved with mechanism of neural tube development.
作者
张瑞苹
舒剑波
赵林胜
蔡春泉
Zhang Ruiping;Shu Jianbo;Zhao Linsheng;Cai Chunquan(Tianjin Children's Hospital,Tianjin 300134,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2019年第8期769-772,共4页
Chinese Journal of Medical Genetics
基金
国家自然科学基金(81771589)
天津市卫生行业重点攻关项目(16KG166)
天津市卫计委科技基金重点项目(2015KR12)
天津市应用基础与前沿技术研究计划(14JCYBJC25000)
天津市重大疾病防治科技重大专项(18ZXDBSY00170).
