DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks.
DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks.
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DOI：
10.1186/s12920-015-0093-1
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发表时间：
2015-05-06
影响因子：
2.7
通讯作者：
Singh SM
中科院分区：
文献类型：
--
作者：
Castellani CA;Laufer BI;Melka MG;Diehl EJ;O'Reilly RL;Singh SM
尽管同卵双胞胎起源单一，但它们在包括精神分裂症在内的复杂疾病方面常常表现出不一致。它是一种常见 (1%) 并且通常是家族性疾病，在同卵双胞胎中不一致率约为 50%。这种高度不一致通常是由未知的环境、随机和表观遗传因素的作用来解释的。 DNA 甲基化参与这种疾病似乎是合乎逻辑的，但仍有待确定。我们使用了两对精神分裂症不一致的同卵双胞胎及其父母的血液 DNA，以便使用 NimbleGen 甲基化启动子微阵列评估全基因组甲基化。全基因组结果表明，代表不一致同卵双胞胎的成员之间存在差异甲基化区域（DMR）。有些 DMR 是与父母共享的，而另一些则似乎是从头开始的。我们发现了 27 个受 DMR 变化影响的基因，这些基因在来自不相关家族的两个不一致的单合子对的受影响成员中共享。有趣的是，受配对特定 DMR 影响的基因共享特定网络。具体来说，这项研究确定了两个网络： “细胞死亡和生存”和“细胞运动和免疫细胞贩运”。这两个网络和受影响的基因先前已被认为与精神分裂症的病因学有关。该结果与 DNA 甲基化可能导致同卵双胞胎精神分裂症不一致的观点相一致。此外，这可能是通过基因特异性甲基化变化对特定生物网络而不是单个基因的直接影响来实现的。它支持精神分裂症涉及广泛的遗传、表观遗传和表型异质性。本文的在线版本 (doi:10.1186/s12920-015-0093-1) 包含补充材料，可供授权用户使用。
Despite their singular origin, monozygotic twin pairs often display discordance for complex disorders including schizophrenia. It is a common (1%) and often familial disease with a discordance rate of ~50% in monozygotic twins. This high discordance is often explained by the role of yet unknown environmental, random, and epigenetic factors. The involvement of DNA methylation in this disease appears logical, but remains to be established. We have used blood DNA from two pairs of monozygotic twins discordant for schizophrenia and their parents in order to assess genome-wide methylation using a NimbleGen Methylation Promoter Microarray. The genome-wide results show that differentially methylated regions (DMRs) exist between members representing discordant monozygotic twins. Some DMRs are shared with parent(s) and others appear to be de novo. We found twenty-seven genes affected by DMR changes that were shared in the affected member of two discordant monozygotic pairs from unrelated families. Interestingly, the genes affected by pair specific DMRs share specific networks. Specifically, this study has identified two networks; “cell death and survival” and a “cellular movement and immune cell trafficking”. These two networks and the genes affected have been previously implicated in the aetiology of schizophrenia. The results are compatible with the suggestion that DNA methylation may contribute to the discordance of monozygotic twins for schizophrenia. Also, this may be accomplished by the direct effect of gene specific methylation changes on specific biological networks rather than individual genes. It supports the extensive genetic, epigenetic and phenotypic heterogeneity implicated in schizophrenia. The online version of this article (doi:10.1186/s12920-015-0093-1) contains supplementary material, which is available to authorized users.
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影响因子：
3.5
作者：
Dempster EL;Pidsley R;Schalkwyk LC;Owens S;Georgiades A;Kane F;Kalidindi S;Picchioni M;Kravariti E;Toulopoulou T;Murray RM;Mill J
通讯作者：
Mill J
影响因子：
5.2
作者：
Bieth, Eric;Eddiry, Sanaa;Tauber, Maithe
通讯作者：
Tauber, Maithe
影响因子：
3.5
作者：
Leung KN;Vallero RO;DuBose AJ;Resnick JL;LaSalle JM
通讯作者：
LaSalle JM
DOI：
10.1073/pnas.0500398102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fraga, MF;Ballestar, E;Esteller, M
通讯作者：
Esteller, M
影响因子：
3.8
作者：
Castellani, Christina A.;Melka, Melkaye G.;Singh, Shiva M.
通讯作者：
Singh, Shiva M.