Epigenetics lessons from twins: prospects for autoimmune disease.
ABSTRACT The existence of phenotypic differences between monozygotic (MZ) twins is a prime case where the relationship between genetic determinants and environmental factors is illustrated. Although virtually identical from a genetic point of view, MZ twins show a variable degree of discordance with respect to different features including susceptibility to disease. Discordance has frequently been interpreted in terms of the impact of the environment with genetics. In this sense, accumulated evidence supports the notion that environmental factors can have a long-term effect on epigenetic profiles and influence the susceptibility to disease. In relation with autoimmune diseases, the identification of DNA methylation changes in individuals who develop the disease, and the influence of inhibitors of DNA methyltransferases and histone modification enzymes in the development of autoimmunity are attracting the attention of researchers in the epigenetics field. In this context, the study of discordant MZ twins constitutes an attractive model to further investigate the epigenetic mechanisms involved in their development as well as to dissect the contribution of environmental traits. The implications of novel strategies to map epigenetic profiles and how the use of MZ twins can contribute to dissect the epigenetic component of autoimmune disease are discussed.
Article: A Snapshot of Histone Modifications within Transposable Elements in Drosophila Wild Type Strains.[show abstract] [hide abstract]
ABSTRACT: Transposable elements (TEs) are a major source of genetic variability in genomes, creating genetic novelty and driving genome evolution. Analysis of sequenced genomes has revealed considerable diversity in TE families, copy number, and localization between different, closely related species. For instance, although the twin species Drosophila melanogaster and D. simulans share the same TE families, they display different amounts of TEs. Furthermore, previous analyses of wild type derived strains of D. simulans have revealed high polymorphism regarding TE copy number within this species. Several factors may influence the diversity and abundance of TEs in a genome, including molecular mechanisms such as epigenetic factors, which could be a source of variation in TE success. In this paper, we present the first analysis of the epigenetic status of four TE families (roo, tirant, 412 and F) in seven wild type strains of D. melanogaster and D. simulans. Our data shows intra- and inter-specific variations in the histone marks that adorn TE copies. Our results demonstrate that the chromatin state of common TEs varies among TE families, between closely related species and also between wild type strains.PLoS ONE 01/2012; 7(9):e44253. · 4.09 Impact Factor
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ABSTRACT: Douglas M Ruden1, Xiangyi Lu21Wayne State University, Department of Obstetrics and Gynecology, C. S. Mott Center for Human Growth and Development, Institute of Environmental Health Sciences, Detroit, MI, USA; 2Institute of Environmental Health Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI, USAAbstract: According to the International Diabetes Federation (IDF), 190 million people worldwide suffer from diabetes, and this number is estimated to double by the year 2025. Diabetes is especially prominent in the elderly population because the IDF indicates age above 45 years as a major risk factor for diabetes. The most common trials for controlling diabetes focus on tighter glucose control as a means to reduce the long-term complications. However, whether tight blood sugar control or other dietary or pharmaceutical interventions in the elderly are more appropriate is not known. Major changes have taken place in our diet over the past 10,000 years since the beginning of the Agricultural Revolution, but our genes have not changed. Furthermore, the large numbers of diabetic elderly in the population are a recent phenomenon, because those with diabetes have historically died young. Genetically speaking, humans today live in a nutritional environment that differs from that for which our genetic constitution was selected. For example a high omega-6/omega-3 ratio, found in today’s Western diets, promotes the pathogenesis of many chronic diseases, including cardiovascular disease and diabetes. Knowing who is at risk would be useful if it meant that one could avoid the environmental triggers that convert susceptibility to disease. The prospect of targeting specific dietary treatments at the elderly, who are predicted to gain the most therapeutic benefits, clearly has important clinical and economic consequences. In this review, we will discuss modern molecular genetic and epidemiological techniques which are now, or soon will be, made available by inexpensive whole-genome sequencing and other whole genome approaches to treat the elderly diabetic population.Keywords: diabetes, elderly diabetic population, DNA, genome sequencingNutrition and Dietary Supplements. 01/2011;
Article: Epigenetics and autoimmune diseases.[show abstract] [hide abstract]
ABSTRACT: Epigenetics is defined as the study of all inheritable and potentially reversible changes in genome function that do not alter the nucleotide sequence within the DNA. Epigenetic mechanisms such as DNA methylation, histone modification, nucleosome positioning, and microRNAs (miRNAs) are essential to carry out key functions in the regulation of gene expression. Therefore, the epigenetic mechanisms are a window to understanding the possible mechanisms involved in the pathogenesis of complex diseases such as autoimmune diseases. It is noteworthy that autoimmune diseases do not have the same epidemiology, pathology, or symptoms but do have a common origin that can be explained by the sharing of immunogenetic mechanisms. Currently, epigenetic research is looking for disruption in one or more epigenetic mechanisms to provide new insights into autoimmune diseases. The identification of cell-specific targets of epigenetic deregulation will serve us as clinical markers for diagnosis, disease progression, and therapy approaches.Autoimmune diseases. 01/2012; 2012:593720.