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Epigenome dynamics: a quantitative genetics perspective

Nature Reviews Genetics volume 9, pages 883–890 (2008)Cite this article

Abstract

Classically, quantitative geneticists have envisioned DNA sequence variants as the only source of heritable phenotypes. This view should be revised in light of accumulating evidence for widespread epigenetic variation in natural and experimental populations. Here we argue that it is timely to consider novel experimental strategies and analysis models to capture the potentially dynamic interplay between chromatin and DNA sequence factors in complex traits.

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Figure 1: DNA sequence and chromatin variation in a segregating population.
Figure 2: Two extreme views of the heritable basis of phenotypic variation.
Figure 3: Classification of epialleles.
Figure 4: Phenotypic variation: a complex case.

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Acknowledgements

We would like to thank R. Breitling for critical comments on previous versions of the manuscript, and Y. Li for her help in preparing the figures. The F.J. and R.C.J. group is supported by the Netherlands Organization for Scientific Research (NWO-ALW VICI grant). V.C. is a NET member of the European Union Epigenome Network of Excellence and is supported by the National Centre for Scientific Research (CNRS), Génoplante and the French Agence Nationale de la Recherche (ANR).

Author information

Authors and Affiliations

  1. Frank Johannes and Ritsert C. Jansen are at the Groningen Bioinformatics Centre, University of Groningen, NL-9751 NN, Haren, The Netherlands.,

    Frank Johannes

  2. Department of Biology, Vincent Colot is at the National Centre for Scientific Research UMR8186, Ecole Normale Supérieure, 75230 Paris Cedex 05, France.,

    Vincent Colot

  3. Department of Genetics NL-9700 RB, Ritsert C. Jansen is also at the University Medical Centre Groningen, Groningen, The Netherlands.,

    Ritsert C. Jansen

Authors
  1. Frank Johannes
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Correspondence to Frank Johannes.

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FURTHER INFORMATION

Arabidopsis Epigenetics and Epigenomics, CNRS

Epigenome Network of Excellence

Groningen Bioinformatics Centre

Glossary

Chromatin

The nucleoprotein structure that packages DNA within the nucleus of eukaryotic cells. The basic unit of chromatin is the nucleosome: a protein core made up of two molecules each of histones H2A, H2B, H3 and H4, around which 146 bp of DNA is wrapped. Different chromatin states are defined by a range of post-translational modifications of core histones, by incorporation of various histone isoforms as well as by DNA methylation.

Complex traits

Continuously distributed phenotypes that are classically believed to result from the independent action of many genes, environmental factors and gene-by-environment interactions.

Epialleles

Alternative chromatin states at a given locus, defined with respect to individuals in the population for a given time point and tissue type. Epialleles vary greatly in their stability and they affect gene expression levels or patterns rather than gene products.

Epigenetic

Refers to the mitotic or meiotic transmissibility of chromatin variation, independent of DNA sequence variation.

Epigenome

The chromatin states that are found along the genome, defined for a given time point and cell type. Thus, for a given genome there may be hundreds or thousands of epigenomes, depending on the stability of chromatin states.

Epigenotype

The epiallelic constitution of a locus.

epiQTLdna

Refers to a QTL influencing chromatin states (epi) in either cis or trans, which can be demonstrated to be due to DNA sequence (dna).

Genetical genomics

The process of relating DNA sequence variation to molecular profile and phenotypic variation.

Heritability

A concept used in quantitative genetics to denote the proportion of total phenotypic variation in a population that is attributable to variation in the heritable material shared between related individuals.

Nucleolus organizer region

(NOR). A chromosomal region characterized by tandem repeats of ribosomal DNA around which the nucleolus forms.

phQTLdna

Refers to a QTL influencing a phenotype (ph), which can be demonstrated to be due to DNA sequence (dna).

phQTLepi

Refers to a QTL influencing a phenotype (ph), which can be demonstrated to be due to chromatin (epi).

Tiling array

A subtype of microarray containing small probes that are designed to cover the entire genome or contigs of the genome in an unbiased manner. These arrays can be used coupled with chromatin immunoprecipitation (ChIP–chip), with methyl-DNA immunoprecipitation (MeDIP–chip) and in DNase chip studies.

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Johannes, F., Colot, V. & Jansen, R. Epigenome dynamics: a quantitative genetics perspective. Nat Rev Genet 9, 883–890 (2008). https://doi.org/10.1038/nrg2467

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