Comprehensive Multiomics Analysis of Monozygotic Twin Discordant for Double Outlet Right Ventricle

IF 1 4区医学 Q4 GENETICS & HEREDITY

Twin Research and Human Genetics Pub Date : 2023-12-15 DOI:10.1017/thg.2023.51

Zhen Liu, Nana Li, Xiaoyu Pan, Jun Li, Shengli Li, Qintong Li, Ping Li, Ying Deng, Fang Chen, Hui Jiang, Wei Wang, Dezhi Mu, Ping Yu, Jun Zhu

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引用次数: 0

Abstract

The objective of this study was to understand and measure epigenetic changes associated with the occurrence of CHDs by utilizing the discordant monozygotic twin model. A unique set of monozygotic twins discordant for double-outlet right ventricles (DORVs) was used for this multiomics study. The cardiac and muscle tissue samples from the twins were subjected to whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and liquid chromatography-tandem mass spectrometry analysis. Sporadic DORV cases and control fetuses were used for validation. Global hypomethylation status was observed in heart tissue samples from the affected twins. Among 36,228 differentially methylated regions (DMRs), 1097 DMRs involving 1039 genes were located in promoter regions. A total of 419 genes, and lncRNA–mRNA pairs involved 30 genes, and 62 proteins were significantly differentially expressed. Multiple omics integrative analysis revealed that five genes, including BGN, COL1A1, COL3A1, FBLN5, and FLAN, and three pathways, including ECM-receptor interaction, focal adhesion and TGF-β signaling pathway, exhibited differences at all three levels. This study demonstrates a multiomics profile of discordant twins and explores the possible mechanism of DORV development. Global hypomethylation might be associated with the risk of CHDs. Specific genes and specific pathways, particularly those involving ECM–receptor interaction, focal adhesion and TGF–β signaling, might be involved in the occurrence of CHDs.

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单卵双胎双出口右心室不一致的多组学综合分析

本研究的目的是利用不一致的单卵双胎模型，了解和测量与先天性心脏病发生相关的表观遗传学变化。这项多组学研究采用了一组独特的双右心室（DORV）不一致单卵双胞胎。对双胞胎的心脏和肌肉组织样本进行了全基因组测序、全基因组亚硫酸氢盐测序、RNA测序和液相色谱-串联质谱分析。零星的 DORV 病例和对照胎儿被用于验证。在受影响双胞胎的心脏组织样本中观察到了全基因低甲基化状态。在 36,228 个差异甲基化区域（DMR）中，有 1097 个涉及 1039 个基因的 DMR 位于启动子区域。共有419个基因和涉及30个基因的lncRNA-mRNA对以及62个蛋白质有显著差异表达。多组学整合分析表明，包括BGN、COL1A1、COL3A1、FBLN5和FLAN在内的5个基因和包括ECM-受体相互作用、病灶粘附和TGF-β信号通路在内的3条通路在所有三个水平上都表现出差异。这项研究展示了不和谐双胞胎的多组学特征，并探索了DORV发生的可能机制。全基因低甲基化可能与先天性心脏病的风险有关。特定的基因和特定的通路，尤其是涉及ECM-受体相互作用、局灶粘附和TGF-β信号传导的基因和通路，可能与CHD的发生有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Twin Research and Human Genetics 医学-妇产科学

CiteScore

1.50

自引率

11.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Twin Research and Human Genetics is the official journal of the International Society for Twin Studies. Twin Research and Human Genetics covers all areas of human genetics with an emphasis on twin studies, genetic epidemiology, psychiatric and behavioral genetics, and research on multiple births in the fields of epidemiology, genetics, endocrinology, fetal pathology, obstetrics and pediatrics. Through Twin Research and Human Genetics the society aims to publish the latest research developments in twin studies throughout the world.