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Epigenetics of Complex Diseases: From General Theory to Laboratory Experiments

  • Chapter
DNA Methylation: Development, Genetic Disease and Cancer

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 310))

Abstract

Despite significant effort, understanding the causes and mechanisms of complex non-Mendelian diseases remains a key challenge. Although numerous molecular genetic linkage and association studies have been conducted in order to explain the heritable predisposition to complex diseases, the resulting data are quite often inconsistent and even controversial. In a similar way, identification of environmental factors causal to a disease is difficult. In this article, a new interpretation of the paradigm of “genes plus environment” is presented in which the emphasis is shifted to epigenetic misregulation as a major etiopathogenic factor. Epigenetic mechanisms are consistent with various non-Mendelian irregularities of complex diseases, such as the existence of clinically indistinguishable sporadic and familial cases, sexual dimorphism, relatively late age of onset and peaks of susceptibility to some diseases, discordance of monozygotic twins and major fluctuations on the course of disease severity. It is also suggested that a substantial portion of phenotypic variance that traditionally has been attributed to environmental effects may result from stochastic epigenetic events in the cell. It is argued that epigenetic strategies, when applied in parallel with the traditional genetic ones, may significantly advance the discovery of etiopathogenic mechanisms of complex diseases. The second part of this chapter is dedicated to a review of laboratory methods for DNA methylation analysis, which may be useful in the study of complex diseases. In this context, epigenetic microarray technologies are emphasized, as it is evident that such technologies will significantly advance epigenetic analyses in complex diseases.

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  1. The Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Rm 28, 250 College St., M4T 1R8, ON, Toronto, Canada

    A. Schumacher & A. Petronis

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  1. A. Schumacher
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  2. A. Petronis
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  1. Institut für Genetik, Universität zu Köln, Zülpicher Str. 47, 50674, Köln, Germany

    Walter Doerfler  & Petra Böhm  & 

  2. Institut für Klinische und Molekulare Virologie, Universität Erlangen, Schlossgarten 4, 91054, Erlangen, Germany

    Walter Doerfler

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Schumacher, A., Petronis, A. (2006). Epigenetics of Complex Diseases: From General Theory to Laboratory Experiments. In: Doerfler, W., Böhm, P. (eds) DNA Methylation: Development, Genetic Disease and Cancer. Current Topics in Microbiology and Immunology, vol 310. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-31181-5_6

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