Environmental Epigenetics Has Potential for Preventing and Treating Disease (2/2/2008)

New research on environmental influences on health and disease has begun to shed light on why genetically identical individuals demonstrate different characteristics, such as susceptibility to disease. Scientists have found that environmental exposure to nutritional, chemical and physical factors can alter the epigenome. Literally meaning "above the genome," the epigenome refers to differences in gene expression that are inherited without changing the sequence of DNA.

An article publishing in the January 2008 issue of Environmental and Molecular Mutagenesis examines some of the epigenetic mechanisms linked to disease, and explores how they occur and their significance in understanding, treating and preventing disease. Environmental and Molecular Mutagenesis, the official journal of the Environmental Mutagen Society, is published by John Wiley & Sons, Inc. and is available online via Wiley InterScience at http://www3.interscience.wiley.com/cgi-bin/jissue/114189787.

Authors Randy L. Jirtle and Dana C. Dolinoy of Duke University Medical Center in Durham, North Carolina, discuss genomic imprinting, a form of gene regulation in which epigenetic modifications in chromosomes result in differences in gene expression. First identified in 1991, there are approximately 80 imprinted genes that have been identified in mice and humans. Because imprinted genes behave as if they have a single set of chromosomes rather than the usual two, the health consequences of mutations in these genes are potentially disastrous, resulting in diseases such as cancer and several severe pediatric developmental disorders. In addition, mutations that occur in non-imprinted regions can influence the regulation of imprinted genes. The authors previously demonstrated that imprinting evolved anywhere from 230 to 150 million years ago, arising in mammals with the evolution of the placenta. They note that the expression of imprinted genes is species, tissue and developmental stage dependent and may play an important role in the speciation of mammals.

The article cites several studies involving metastable epialleles, which are alternate forms of a gene that are expressed due to epigenetic modifications linked to maternal nutrition and environmental exposure during very early development. The authors note that simple dietary changes were found to protect against the negative effects of environmental toxins on the fetal epigenome. They also cite evidence that embryos are vulnerable to environmentally-induced epigenetic alterations early in their development, highlighting the need to analyze the timing of exposure in order to fully understand environmental epigenomics.

The advent of bioinformatics has allowed researchers to more readily search the entire mouse genome for imprinted genes, but the real power of this approach has been recently demonstrated in its application to the human genome. While 2.5 percent of the mouse genome contains potentially imprinted genes, only 0.75 percent of the human genome is predicted to be imprinted. This means that the mouse genome may not be a suitable model for assessing human disease risk due to epigenetic mutations in imprinted genes. The authors point out the necessity of developing bioinformatic models that can identify metastable epialleles in order to characterize all of the genes susceptible to environmental influences.

With the identification of epigenetically unstable locations in the human genome, it will be possible to screen individuals at an early age for epigenetically susceptible diseases, allowing for closer monitoring and more frequent follow-up. In addition, unlike genetic mutation, epigenetic profiles are potentially reversible. "Therefore, epigenetic approaches for prevention and treatment, such as nutritional supplementation and/or pharmaceutical therapies may be developed to counteract negative epigenomic profiles," the authors conclude. "The future of epigenomics therapy holds tremendous potential for not only individualized health care but also for population-wide disease diagnostic, screening, and prevention strategies."

Article: "Environmental Epigenomics in Human Health and Disease," Dana C. Dolinoy and Randy L. Jirtle, Environmental and Molecular Mutagenesis

Note: This story has been adapted from a news release issued by Blackwell Publishing

Post Comments: