University of Groningen Assessing the Impact of Transgenerational Epigenetic Variation on Complex Traits
University of Groningen Assessing the Impact of Transgenerational Epigenetic Variation on Complex Traits
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2009
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通讯作者：
F. Johannes;E. Porcher;F. K. Teixeira;V. Saliba-Colombani;M. Simon;Nicolas Agier;Agnès Bulski;J. Albu
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作者：
F. Johannes;E. Porcher;F. K. Teixeira;V. Saliba-Colombani;M. Simon;Nicolas Agier;Agnès Bulski;J. Albu
DNA甲基化的丧失或获得会影响基因表达，有时会跨代传播。因此，这种表观遗传改变是在没有DNA序列改变的情况下可遗传表型变异的可能来源。然而，试图评估自然和实验人群中稳定的表观遗传变异的流行程度，并量化其对复杂性状的影响，受到了DNA序列多态性的混淆效应的阻碍。为了尽可能地克服这个问题，使用具有很少DNA序列差异但DNA甲基化谱相反的两个亲本在参考植物拟南芥中衍生一组表观遗传重组近交系（epiRILs）。这些表观基因序列在开花时间和株高上表现出变异和高遗传力（30%），以及多个亲本DNA甲基化变体（表观等位基因）在至少8代中的稳定遗传。这些发现提供了第一个基本原理，以确定表观等位基因变异，有助于遗传变异的复杂性状，使用连锁或关联研究。更一般地说，在没有选择或广泛的DNA序列变异的情况下，基因组中的许多表观等位基因可以在许多代中保持稳定，这一事实突出了将表观遗传信息整合到群体遗传学研究中的必要性。引文：Johannes F，Porcher E，特谢拉FK，Saliba-Colombani V，Simon M，et al.（2009）评估跨代表观遗传变异对复杂性状的影响。PLoS Genet 5（6）：e1000530。doi：10.1371/journal.pgen.1000530编辑：Peter M. Visscher，昆士兰州医学研究所，澳大利亚接收日期：2009年4月15日;接受日期：2009年5月22日;发表日期：2009年6月26日版权所有：2009 Johannes et al.这是一篇开放获取的文章，根据知识共享署名许可证的条款分发，该许可证允许在任何媒体上无限制地使用，分发和复制，但须注明原作者和来源。资金来源：EP和VSC获得了Genoplante博士后奖学金，FJ获得了短期玛丽居里培训奖学金（欧洲联盟），FKT获得了CAPES（Coordenação de Pessoal de Niâvel上级，巴西）博士奖学金，F.来自欧盟卓越网络“表观基因组”的博士后奖学金的Heredia。这项工作得到了Genoplante（VC，Frédéric Hospital和PG）和欧盟卓越网络“表观基因组”（VC）的资助。资助者在研究设计、数据收集和分析、出版决定或手稿编写中没有任何作用。利益冲突：作者声明不存在利益冲突。* 电子邮件：Frederic. Hospital@www.example.com（FH）; www.example.com（VC）<$a当前地址：Aguatoire Conservation des Espèces，Restauration et Suivi des Populations，CNRS UMR 7204，Muséum National d'Histoire Naturelle，Université Pierre et Marie Curie，Paris，France <$b当前地址：Génomique des microorganismes，Université Pierre et Marie Curie，CNRS FRE 3214，Paris，France <$c当前地址：jouy.inra.fr这些作者对这项工作作出了同样的贡献。
Loss or gain of DNA methylation can affect gene expression and is sometimes transmitted across generations. Such epigenetic alterations are thus a possible source of heritable phenotypic variation in the absence of DNA sequence change. However, attempts to assess the prevalence of stable epigenetic variation in natural and experimental populations and to quantify its impact on complex traits have been hampered by the confounding effects of DNA sequence polymorphisms. To overcome this problem as much as possible, two parents with little DNA sequence differences, but contrasting DNA methylation profiles, were used to derive a panel of epigenetic Recombinant Inbred Lines (epiRILs) in the reference plant Arabidopsis thaliana. The epiRILs showed variation and high heritability for flowering time and plant height (,30%), as well as stable inheritance of multiple parental DNA methylation variants (epialleles) over at least eight generations. These findings provide a first rationale to identify epiallelic variants that contribute to heritable variation in complex traits using linkage or association studies. More generally, the demonstration that numerous epialleles across the genome can be stable over many generations in the absence of selection or extensive DNA sequence variation highlights the need to integrate epigenetic information into population genetics studies. Citation: Johannes F, Porcher E, Teixeira FK, Saliba-Colombani V, Simon M, et al. (2009) Assessing the Impact of Transgenerational Epigenetic Variation on Complex Traits. PLoS Genet 5(6): e1000530. doi:10.1371/journal.pgen.1000530 Editor: Peter M. Visscher, Queensland Institute of Medical Research, Australia Received April 15, 2009; Accepted May 22, 2009; Published June 26, 2009 Copyright: 2009 Johannes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: EP and VSC were recipients of Genoplante post-doctoral fellowships, FJ of a short-term Marie Curie training studentship (European Union), FKT of a CAPES (Coordenação de Aperfeiçoamento de Pessoal de Niâ-vel Superior, Brazil) PhD studentship, and F. Heredia of a post-doctoral fellowship from the European Union Network of Excellence ‘‘The Epigenome.’’ This work was funded by grants from Genoplante (to VC, Frédéric Hospital, and PG), and the European Union Network of Excellence ‘‘The Epigenome’’ (to VC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: Frederic.Hospital@jouy.inra.fr (FH); colot@biologie.ens.fr (VC) ¤a Current address: Laboratoire Conservation des Espèces, Restauration et Suivi des Populations, CNRS UMR 7204, Muséum National d’Histoire Naturelle, Université Pierre et Marie Curie, Paris, France ¤b Current address: Génomique des microorganismes, Université Pierre et Marie Curie, CNRS FRE3214, Paris, France ¤c Current address: Laboratoire de Génétique Moléculaire, Centre Hospitalier Universitaire Hôtel-Dieu, Nantes, France . These authors contributed equally to this work.