Genome and epigenome analysis of monozygotic twins discordant for congenital heart disease
Guoliang Lyu,
Chao Zhang,
Te Ling,
Rui Liu,
Le Zong,
Yiting Guan,
Xiaoke Huang,
Lei Sun,
Lijun Zhang,
Cheng Li,
Yu Nie,
Wei Tao
Affiliations
Guoliang Lyu
Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University
Chao Zhang
Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University
Te Ling
Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University
Rui Liu
Department of Cardiovascular Surgery, Center for Cardiovascular Regenerative Medicine, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences
Le Zong
Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University
Yiting Guan
Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University
Xiaoke Huang
Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University
Lei Sun
Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University
Lijun Zhang
Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University
Cheng Li
Center for Bioinformatics, School of Life Sciences, Peking University
Yu Nie
Department of Cardiovascular Surgery, Center for Cardiovascular Regenerative Medicine, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences
Wei Tao
Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University
Abstract Background Congenital heart disease (CHD) is the leading non-infectious cause of death in infants. Monozygotic (MZ) twins share nearly all of their genetic variants before and after birth. Nevertheless, MZ twins are sometimes discordant for common complex diseases. The goal of this study is to identify genomic and epigenomic differences between a pair of twins discordant for a form of congenital heart disease, double outlet right ventricle (DORV). Results A monoamniotic monozygotic (MZ) twin pair discordant for DORV were subjected to genome-wide sequencing and methylation analysis. We identified few genomic differences but 1566 differentially methylated regions (DMRs) between the MZ twins. Twenty percent (312/1566) of the DMRs are located within 2 kb upstream of transcription start sites (TSS), containing 121 binding sites of transcription factors. Particularly, ZIC3 and NR2F2 are found to have hypermethylated promoters in both the diseased twin and additional patients suffering from DORV. Conclusions The results showed a high correlation between hypermethylated promoters at ZIC3 and NR2F2 and down-regulated gene expression levels of these two genes in patients with DORV compared to normal controls, providing new insight into the potential mechanism of this rare form of CHD.