University of Groningen Assessing the Impact of Transgenerational Epigenetic Variation on Complex Traits

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.