O. Tollefsbol Personalized Epigenetics

1. Auflage 2015
ISBN: 978-0-12-800436-4
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 610 Seiten

Personalized Epigenetics discusses the core translatability of epigenetics to health management of individuals who have unique variations in their epigenetic signatures that can guide both disorder and disease prevention and therapy. The book details inter-individual variability in the major epigenetic process in humans consisting of DNA methylation, histone modifications, and noncoding RNA, and the diagnostic, prognostic, and therapeutic potential of the field, it also reviews the impact of the environment on epigenetic variations among individuals and the role of pharmacology and drug development in personalized epigenetics. Most importantly, the text covers personalized epigenetics from a disease-oriented perspective, presenting chapters that provide advances in widespread disorders or diseases, including diabetes, cancer, autoimmune disorders, obesity, cardiovascular diseases, neurological disorders, and pain management. - Discusses the core translatability of epigenetics to health management of individuals who have unique variations in their epigenetic signatures - Details inter-individual variability in the major epigenetic process in humans consisting of DNA methylation, histone modifications, and noncoding RNA, and the consequent diagnostic, prognostic and therapeutic potential of the field - Reviews the impact of the environment on epigenetic variations among individuals and the roles of pharmacology and drug development - Devotes several chapters to the advances made in widespread disorders or diseases, including diabetes, cancer, autoimmune disorders, obesity, cardiovascular diseases, neurological disorders, and pain management

Autoren/Hrsg.

O. Tollefsbol, Trygve

Leseproben

Chapter 1 Epigenetics of Personalized Medicine
Trygve O. Tollefsbol1,2,3,4,5     1Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA     2Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA     3Comprehensive Center for Healthy Aging, University of Alabama at Birmingham, Birmingham, AL, USA     4Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL, USA     5Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL, USA Abstract
Interindividual variability in epigenetic processes is often formed through environmental influences that shape the epigenome, and these epigenetic signatures can be translated to assist disease prevention or therapy. Since epigenetic aberrations often span across the genome, analysis of the epigenome through computational epigenetics has gained increasing attention as a means to identify key epigenetic changes that allow diseases to form and progress. Many medical conditions have an epigenetic basis and are therefore amenable to management through personalized epigenetic analyses. Drug development, responses to changes in nutrition, toxicity, and forensics also have high potential for analysis of epigenetic signatures. It is apparent that personalized epigenetics is on the horizon of advances that could significantly improve the management of many disorders and diseases that are currently presenting persistent challenges to more conventional approaches to medicine. Keywords
DNA methylation; Epigenetic; Histone modification; Medicine; Noncoding RNA; Personalized Outline 1. Introduction 4 2. Epigenetic Variations Among Individuals 4 3. Bioinformatics of Personalized Epigenetics 6 4. Diagnostic and Prognostic Epigenetic Approaches to Personalized Medicine 6 5. Environmental Personalized Epigenetics 8 6. Pharmacology and Drug Development of Personalized Epigenetics 8 7. Personalized Epigenetics of Disorders and Disease Management 9 8. Challenges and Future Directions 11 9. Conclusion 11 References 12 1. Introduction
While each species, cell, and system has a characteristic epigenetic profile, individuals also have an epigenetic profile that forms their unique epigenome. Epigenetic aberrations are known to play a key role in many human diseases, and the purpose of personalized epigenetics is to base medical prevention and therapeutics as well as diagnostics and prognostics on the distinctive health and disease susceptibility profile of each individual. In fact, interindividual differences in the epigenome are the basis of personalized epigenetics and these can manifest through epigenetic signatures that are characteristic of each individual. DNA methylation, for example, varies between individuals [1–2] as do the many different forms of epigenetic histone modifications [3–4]. In addition, noncoding RNA profiles are also variable from person to person [5–6]. These variations in epigenetic expression will undoubtedly become increasingly important as the potential for personalized epigenetics in medicine continues to grow. Personalized epigenetics can serve as a guide not only for the therapy of epigenetic-based diseases, but also for many other aspects of medicine. Epigenetic biomarkers comprising epigenomic signatures unique to each individual have increasingly been shown to provide not only valuable information with respect to the diagnosis of disorders and diseases, but also prognostic information pertaining to the likely progression of diseases such as cancer [7–8]. There are also many applications of personalized epigenetics in forensics and in toxicology. Many toxic compounds leave distinct epigenomic signatures that could have significant utility in terms of diagnosing toxicity as well as treatment of patients that have been exposed to toxins [9–10]. Similar concepts apply to environmental contaminants [11–12] and nutrients [13–14] that also have an impact on the epigenome. Equally exciting is the prospect of application of personalized epigenetics to the many disorders and diseases that have epigenetic aberrations as a component of their etiology or pathogenesis. For example, epigenetic alterations have been shown in a number of studies to be important in chronic pain, and studies are emerging that may lead to personalized management of pain based on the distinct epigenomic profile of the individual patient [15–16]. Approaches to patient management through personalized epigenetics are also rapidly developing for many other medical conditions such as obesity, cancer, autoimmune disorders, and cardiovascular diseases. 2. Epigenetic Variations among Individuals
One of the most important components of the collective epigenetic changes that occur in cells and tissues is DNA methylation. The role of DNA methylation in modulating gene expression has been known for quite some time, although it has been more recently appreciated that it can vary considerably between individuals within a species. As Watanabe and Riddle explain in Chapter 2, the variation in DNA methylation between individuals is a common feature ranging from plants to humans. There are a number of possible causes for extensive variance of DNA methylation among individuals, including gender, health status, age, and environmental exposures, as well as many other factors. The heterogeneity of DNA methylation patterns within individuals is of particular interest to those focused on personalized medicine. For example, interindividual differences in DNA methylation have considerable potential as a biomarker for a number of diseases as well as a means to guide therapy for diseases such as cancer. In fact, the optimal drug dosage that is administered to individual patients could be monitored through changes in the patient’s DNA methylation profile, which serves as a classic example of the utility of knowledge of personalized epigenetics as applied to medicine, as reviewed in Chapter 2. There are many different types of histone modifications that can modulate epigenetic gene expression of an organism and these modifications are also subject to interindividual variation. The importance of individual heterogeneity of histone modifications as well as techniques such as mapping of DNase I-hypersensitive sites and formaldehyde-assisted isolation of regulatory elements (FAIRE) and chromatin immunoprecipitation (ChIP), as well as their genomic counterparts (DNase-seq, FAIRE-seq, and ChIP-seqA), is highlighted in Chapter 3. Especially fascinating is the prospect of the potential use of induced pluripotent stem cells for elucidating chromatin modifications and transcription differences in healthy and disease states as a “bottom-up” approach (Chapter 3) to advance our knowledge of chromatin heterogeneity between individuals and the potential application of this knowledge to personalized medicine. Noncoding RNA (ncRNA) variations have great importance to personalized epigenetics since ncRNAs such as microRNAs (miRNAs), trinucleotide repeats, and long noncoding RNAs not only regulate epigenetic processes, but are in turn regulated by epigenetic processes as well. Variation in ncRNA sequences can modulate not only RNA stability, but also its processing, which can affect the regulatory capacity of ncRNAs. As delineated in Chapter 4, these differences in ncRNAs between individuals can lead to major epigenetic changes in disease processes and may also have utility as biomarkers of various diseases. For example, there is some evidence that miRNA expression signatures may distinguish Alzheimer’s disease and Parkinson’s disease from normal controls (Chapter 4). Moreover, variations of ncRNAs between individuals could be employed for personalized medical therapy through monitoring of drug responses. Despite great excitement in the potential uses of interindividual epigenetic variations in personalized medicine, there are some limitations that must be overcome. For instance, there can be challenges in detecting true epi-mutations, and epigenetic signatures vary not only among individuals, but also between the various cell types within individuals (Chapter 5). There can also be complications with respect to allele-specific or asymmetric DNA methylation changes that can add to the complexity of interpretations of epigenetic differences between individuals. Nevertheless, it is apparent that interindividual differences in epigenetic processes such as DNA methylation is substantial and the collective pattern differences in response to medical interventions have considerable promise in leading to many advances in medical diagnosis, prognosis, and therapy. 3. Bioinformatics of Personalized Epigenetics
Although the heterogeneity of epigenetic events presents a challenge in monitoring reliable changes in epigenetic patterns between individuals and in response to medical interventions, computational epigenetics provides many solutions to this challenge. Chapter 6 reviews the data types most often used in epigenetic studies and their use in medicine. Computational approaches to DNA methylation patterns, histone modifications, and ncRNAs as well as quantitative protein...