Genome and epigenome analysis of monozygotic twins discordant for congenital heart disease.
Genome and epigenome analysis of monozygotic twins discordant for congenital heart disease.
复制标题
先天性心脏病不一致的同卵双胞胎的基因组和表观基因组分析
DOI：
10.1186/s12864-018-4814-7
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发表时间：
2018-06-04
期刊：
影响因子：
4.4
通讯作者：
Tao W
中科院分区：
文献类型：
--
作者：
Lyu G;Zhang C;Ling T;Liu R;Zong L;Guan Y;Huang X;Sun L;Zhang L;Li C;Nie Y;Tao W
先天性心脏病（CHD）是导致婴儿死亡的主要非感染性原因。同卵双胞胎（MZ）在出生前后几乎共享所有的遗传变异。然而，同卵双胞胎有时在常见的复杂疾病上不一致。本研究的目的是确定一对先天性心脏病双出口右心室（DORV）双胞胎之间的基因组和表观基因组差异。对DORV不一致的单羊膜单卵（MZ）双胞胎进行全基因组测序和甲基化分析。我们确定了几个基因组差异，但1566差异甲基化区域（DMR）之间的MZ双胞胎。20%（312/1566）的DMR位于转录起始位点（TSS）上游2kb以内，包含121个转录因子结合位点。特别地，发现ZIC 3和NR 2F 2在患病双胞胎和患有DORV的其他患者中具有高甲基化的启动子。结果显示，与正常对照相比，DORV患者ZIC 3和NR 2F 2的高甲基化启动子与这两个基因的下调基因表达水平之间存在高度相关性，为这种罕见形式的CHD的潜在机制提供了新的见解。本文的在线版本（10.1186/s12864-018-4814-7）包含补充材料，可供授权用户使用。
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). 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. 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. The online version of this article (10.1186/s12864-018-4814-7) contains supplementary material, which is available to authorized users.
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影响因子：
7.7
作者：
Caramori ML;Kim Y;Moore JH;Rich SS;Mychaleckyj JC;Kikyo N;Mauer M
通讯作者：
Mauer M
DOI：
10.1093/bioinformatics/btr670
发表时间：
2012-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Boeva V;Popova T;Bleakley K;Chiche P;Cappo J;Schleiermacher G;Janoueix-Lerosey I;Delattre O;Barillot E
通讯作者：
Barillot E
影响因子：
16.6
作者：
Arora M;Reichenberg A;Willfors C;Austin C;Gennings C;Berggren S;Lichtenstein P;Anckarsäter H;Tammimies K;Bölte S
通讯作者：
Bölte S
影响因子：
9.8
作者：
Chen, Xu;Kuja-Halkola, Ralf;Magnusson, Patrik K. E.
通讯作者：
Magnusson, Patrik K. E.
影响因子：
20.1
作者：
Fahed AC;Gelb BD;Seidman JG;Seidman CE
通讯作者：
Seidman CE