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Epigenetics


EPIGENETICS targeting the mediator


between environment and phenotype


Although it is still early days in terms of our understanding of epigenetics, the fast development of new tools and technologies to define genome-wide epigenetic variations in humans has the potential to enable effective new epigenetic therapies and diagnostic tests for a wide range of diseases beyond and including cancer.


I


t is well known that the bad habits of an indi- vidual such as overeating or cigarette smoking are likely to result in a shorter life span for that individual. Recent studies in epigenetics suggest that at least some of these bad behaviours may also impact the health of that individual’s progeny to disease. The Överkalix study (an isolated commu- nity in northern Sweden) found that a single win- ter of overeating as a child can biologically predis- pose one’s children and grandchildren to diabetes and heart disease, resulting in lifespans that are decades shorter than their peers1. The Avon Longitudinal Study of Parents and Children (ALSPAC) found that sons and grandsons of men who smoke during pre-puberty are at greater risk for obesity and other health problems2. How is it possible that a decision made by a child can have such catastrophic consequences for multiple gener- ations of offspring so quickly? Conventional wis-


Drug Discovery World Fall 2011


dom traditionally held that all heredity was speci- fied by the genetic information encoded in an indi- vidual’s DNA sequence and acquired changes in cell behaviour were due to changes in that sequence over time. However, observations such as those found in the Överkalix and ALPAC studies occurred far too quickly to be explained by natural selection; genetic mutations are clearly not the entire story.


Epigenetics is a second layer of hereditary infor- mation that causes changes in gene expression pat- terns. These changes are not a result of mutations to the DNA sequence itself, but instead result from environmental factors that alter expression through chemical modification of the DNA and chromatin associated proteins. These types of changes (partic- ularly methylation of DNA) may also explain dif- ferences in phenotypes of identical twins3. Epigenetics is ubiquitous in nature, occurring in


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By Dr John M. Rosenfeld,


Dr Kan Saito and Dr Michael Sturges

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