Two epigenomic targets that potentially link environmental exposures to chemical and physical agents early in development to adult disease susceptibility are imprinted genes and those with metastable epialleles. Genes with metastable epialleles, such as the Agouti locus in the agouti viable yellow (Avy) strain of mice, have highly variable functions because of stochastic allelic changes in the epigenome rather than mutations in the genome. Genomic imprinting is an unique epigenetic form of gene regulation that evolved about 150 million years ago in mammals with the development of the placenta and the advent of viviparity. It results in monoallelic, parent-of-origin dependent gene silencing. Thus, only a single genetic or epigenetic event is required to alter the function of an imprinted gene. The potential importance of these two novel subsets of epigenetically labile genes in the etiology of environmentally-induced diseases will be discussed.
Professor Randy L. Jirtle headed the epigenetics and imprinting laboratory at Duke University until 2012. He is now a Professor of Epigenetics in the Department of Biological Sciences at North Carolina State University, Raleigh, NC, and a Senior Scientist in the McArdle Laboratory for Cancer Research at the University of Wisconsin, Madison, WI. Jirtle’s research interests are in epigenetics, genomic imprinting, and the fetal origins of disease susceptibility. He has published over 200 peer-reviewed articles, and was a featured scientist on the NOVA television program on epigenetics entitled Ghost in Your Genes. He has delivered numerous endowed lectures, and was invited to speak at the 2004 Nobel Symposia on Epigenetics. He was honored in 2006 with the Distinguished Achievement Award from the College of Engineering at the University of Wisconsin-Madison. In 2007, Jirtle was nominated for Time Magazine’s “Person of the Year.” He was the inaugural recipient of the Epigenetic Medicine Award in 2008, and received the STARS Lecture Award in Nutrition and Cancer from the National Cancer Institute in 2009. Jirtle was invited in 2010 to participate in the Aspen Ideas Festival in Colorado, and the Nestlé’s 7th International Nutrition Symposium in Switzerland. Jirtle organized the Keystone Environmental Epigenomics and Disease Susceptibility meeting, received the EHP Classic Paper of the Year Award, and was invited to speak again in the Nobel Forum at an epigenomics symposium sponsored by The Nobel Assembly at the Karolinska Institutet in Stockholm in 2011. Dr. Jirtle was invited in 2012 to present the NIH Director’s WALS lecture. Jirtle participated in the World Science Festival in New York, gave the Killam Lecture at Dalhousie University, and published two books on Environmental Epigenomics in Health and Disease in 2013. Dr. Jirtle received the Jean Andrews Centennial Faculty Fellowship in Human Nutrition from the University of Texas-Austin, delivered the Robert B. Church Lecture In Biotechnology at the University of Calgary, and received the Linus Pauling Award from the Institute of Functional Medicine in 2014. In 2016, Jirtle delivered the commencement address in the Department of Biological Sciences at North Carolina State University. ShortCutsTV did an English documentary in 2017, Are You What Your Mother Ate? The Agouti Mouse Study, that is based upon Jirtle’s epigenetic research.