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Epigenetics in Human Disease
 
 

Epigenetics in Human Disease, 1st Edition

 
Epigenetics in Human Disease, 1st Edition,Trygve Tollefsbol,ISBN9780123884152
 
 
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T Tollefsbol   

Academic Press

9780123884152

9780123884169

592

276 X 216

A complete survey of the emerging field of epigenetics in the etiology, progression, diagnosis, prognosis and treatment of a wide range of human diseases

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Key Features

  • Comprehensive coverage of fundamental and emergent science and clinical usage
  • Side-by-side coverage of the basis of epigenetic diseases and their treatments
  • Evaluation of recent epigenetic clinical breakthroughs

Description

Epigenetics is one of the fastest growing fields of sciences, illuminating studies of human diseases by looking beyond genetic make-up and acknowledging that outside factors play a role in gene expression. The goal of this volume is to highlight those diseases or conditions for which we have advanced knowledge of epigenetic factors such as cancer, autoimmune disorders and aging as well as those that are yielding exciting breakthroughs in epigenetics such as diabetes, neurobiological disorders and cardiovascular disease. Where applicable, attempts are made to not only detail the role of epigenetics in the etiology, progression, diagnosis and prognosis of these diseases, but also novel epigenetic approaches to the treatment of these diseases. Chapters are also presented on human imprinting disorders, respiratory diseases, infectious diseases and gynecological and reproductive diseases. Since epigenetics plays a major role in the aging process, advances in the epigenetics of aging are highly relevant to many age-related human diseases. Therefore, this volume closes with chapters on aging epigenetics and breakthroughs that have been made to delay the aging process through epigenetic approaches. With its translational focus, this book will serve as valuable reference for both basic scientists and clinicians alike.

Readership

Researchers working in basic molecular biology, genetics, and clinical therapy who are interested in either the underlying basis of human diseases or novel means to treat human diseases; advanced undergraduate students, graduate students, university researchers, pharmaceutical company and biotechnology researchers interested in drug development and therapies.

Trygve Tollefsbol

Professor of Biology, University of Alabama at Birmingham, Birmingham, AL. Dr. Tollefsbol is a Professor of Biology and a Senior Scientist in the Center for Aging, Comprehensive Cancer Center, Nutrition Obesity Research Center, and the Comprehensive Diabetes Center at the University of Alabama at Birmingham (UAB). He is Director of the UAB Cell Senescence Culture Facility which he established in 1999 and a Steering Committee Member of the UAB Center for Aging. Dr. Tollefsbol trained as a Postdoctoral Fellow and Assistant Research Professor with members of the National Academy of Science at Duke University and the University of North Carolina. He earned doctorates in molecular biology and osteopathic medicine from the University of North Texas Health Sciences Center and his bachelor’s degree in Biology from the University of Houston. He has received prior funding from the NIA, NCI, NHLBI, NIMH and other federal institutes as well as the Glenn Foundation for Medical Research, Susan G. Komen for the Cure, the American Federation for Aging Research (AFAR), and the American Institute for Cancer Research (AICR) among many other sources. The Glenn Foundation for Medical Research funding was unsolicited and was awarded to Dr. Tollefsbol for lifetime contributions to the field of aging. In 2006 Dr. Tollefsbol was selected and highlighted as part of the 25th anniversary of the AFAR for significant contributions to aging research. Dr. Tollefsbol’s research interests have covered a wide range of topics such as aging, epigenetics, nutrition, cancer, telomerase, and caloric restriction. Work from his laboratory has been featured in Women’s Health magazine, Shape magazine, and the AICR Newsletter and Dr. Tollefsbol has been a Scientist in the Spotlight in ScienceNow. Currently he serves as an Associate Editor for Frontiers in Epigenomics and is on the Editorial Boards of the international journals Open Longevity Science, Epigenetics of Diabetes and Obesity, Molecular Biotechnology and Clinical Epigenetics. He is also a contributing Editor of Lewin’s GENES X classic textbook. Over 25 of the publications from Dr. Tollefsbol’s laboratory have received national or international accolades such as best paper award, selection for press release by the journal editors and featured on the journal homepage. Dr. Tollefsbol has been invited to give presentations on his research in many countries including Germany, China, Italy, Switzerland, France and The Netherlands as well as at various leading institutions in the US such as Harvard Medical School, Tufts University and the University of California at San Francisco. His research has received considerable media attention both nationally and internationally through television, newspaper and radio venues and has been highlighted in eScience News and ScienceDaily. He has ten books which have been published or are in progress and a recent book on “Epigenetics of Aging” that Dr. Tollefsbol co-authored and edited was highlighted in Nature.

Affiliations and Expertise

Professor of Biology, University of Alabama at Birmingham, AL, USA

View additional works by Trygve Tollefsbol

Epigenetics in Human Disease, 1st Edition

Preface

Contributors

Chapter 1. Epigenetics of Human Disease

1.1 Introduction

1.2 Epigenetic Variation Methods

1.3 Cancer Epigenetics

1.4 Epigenetics of Neurological Disease

1.5 Autoimmunity and Epigenetics

1.6 Human Imprinting Disorders

1.7 Epigenetics of Obesity

1.8 Diabetes: The Epigenetic Connection

1.9 Epigenetics and Allergic Disorders

1.10 Cardiovascular Disease and Epigenetics

1.11 Epigenetics of Human Infectious Diseases

1.12 Reproductive Disorders and Epigenetic Aberrations

1.13 Stem Cell Epigenetics in Human Disease

1.14 Epigenetics of Aging and Age-Associated Diseases

1.15 Conclusion

References

Chapter 2. Methods and Strategies to Determine Epigenetic Variation in Human Disease

2.1 Introduction

2.2 DNA Methylation Analysis

2.3 Histone Modification Analysis

2.4 Non-Coding RNA Analysis: MicroRNA

2.5 Analysis of Genome DNA Replication Program Based on DNA Replication Timing

2.6 Strategy for Epigenomic Investigation Based on Chromosomal Band Structures

2.7 Overview of Recent Epigenetic genome-Wide or Bioinformatic Studies and Strategies

2.8 General Overview and Future Perspective

References

Chapter 3. DNA Methylation Alterations in Human Cancers

3.1 Introduction: Biological Roles of DNA Methylation

3.2 DNA Methylation Alterations in Human Cancers

3.3 Aberrant DNA Methylation in Precancerous Conditions Associated with Chronic Inflammation, Persistent Viral Infection and Smoking

3.4 Abnormal Expression of DNMTs in Human Cancers

3.5 Mutations, Polymorphism and Splicing Alterations of DNMTs and Human Cancers

3.6 Signal Pathways Affecting DNA Methylation Status During Tumorigenesis

3.7 DNA Methylation and Histone Modifications

3.8 Subclassification of Human Cancers Based on DNA Methylation Profiling

3.9 Diagnosis of Cancers in Body Fluids and Biopsy Specimens Based on DNA Methylation Profiles

3.10 Carcinogenetic Risk Estimation Based on DNA Methylation Profiles

3.11 Personalized Medicine Based on DNA Methylation Profiles: Prognostication of Patients with Cancers and Prediction of Response to Chemotherapy

3.12 New Technologies for DNA Methylation Analysis and Future Directions

References

Chapter 4. Alterations of Histone Modifications in Cancer

4.1 Introduction

4.2 Chromatin Organization

4.3 Histone Modifications

4.4 Histone Modifications and Cancer

4.5 Mechanisms Underlying Histone Alterations in Cancer

4.6 Conclusions

References

Chapter 5. MicroRNA in Oncogenesis

5.1 Introduction

5.2 miRNA Biogenesis

5.3 miRNA-Mediated Regulation of Targets

5.4 miRNA and Cancer

5.5 OncomiRs

5.6 Mechanisms of miRNA Deregulation

5.7 miRNA and Treatment Resistance

5.8 Clinical Applications

References

Chapter 6. Epigenetic Approaches to Cancer Therapy

6.1 Introduction

6.2 Histone Acetylation

6.3 Histone Deacetylases

6.4 Histone Methylation and Demethylation

6.5 DNA Methylation

6.6 Acetylation of Non-Histone Proteins

6.7 Future Directions

References

Chapter 7. Epigenomics in Neurobehavioral Diseases

7.1 Introduction

7.2 What is the Epigenome?

7.3 Epigenomic Modulation of Chromatin

7.4 Issues Unique to Neurobehavioral Diseases

7.5 Genetics

7.6 Environment

7.7 Genomic Instability

7.8 Transcriptional Dysregulation

7.9 RNA Epigenomics

7.10 Metabolism

7.11 Nutritional and Drug Interventions

7.12 Putting it all Together

Glossary

Acknowledgments

References

Chapter 8. Emerging Role of Epigenetics in Human Neurodevelopmental Disorders

8.1 Introduction: Few Neurodevelopmental Disorders have Epigenetic Defects

8.2 Components of the Epigenetic Machinery

8.3 Neurodevelopmental Disorders due to Defects in Epigenetic Machinery

8.4 Neurodevelopmental Disorders due to Aberrant Epigenetic Patterns

8.5 Maternal Duplications versus Paternal Duplications in PWS/AS Region

8.6 Conclusions

References

Chapter 9. The Epigenetics of Alzheimer’s Disease

9.1 Alzheimer's Disease

9.2 One-Carbon Metabolism and DNA Methylation in Alzheimer’s Disease

9.3 Histone Tail Modifications and Alzheimer’s Disease

9.4 RNA-Mediated Mechanisms and Alzheimer’s Disease

9.5 Discussion and Conclusions

References

Chapter 10. Epigenetic Modulation of Human Neurobiological Disorders

10.1 Introduction

10.2 Epigenetic Mechanism Associated with Congenital Neurobiological Disorders

10.3 Epigenetic Mechanism Underlying Alteration of the Brain Function by Environmental Factors

10.4 Transgenerational Epigenetic Inheritance (Non-Mendelian Disease Inheritance)

10.5 Epigenetic Medicine for Neurobiological Disorders

10.6 Conclusion

References

Chapter 11. Epigenetic Basis of Autoimmune Disorders in Humans

11.1 Immunity and Autoimmunity

11.2 Epigenetic Deregulation in Autoimmunity

11.3 Conclusions

References

Chapter 12. Approaches to Autoimmune Diseases Using Epigenetic Therapy

12.1 Introduction

12.2 Pathophysiologic Basis for the Development of Epigenetic Treatments in Autoimmunity

12.3 Pathology of Autoimmune Disease and Potential Targets for Epigenetic Drugs

12.4 HDAC Inhibitors

12.5 DNA Methylation and DNA Methyltransferases

12.6 MicroRNA

12.7 Antagomirs

12.8 Techniques to Measure Epigenetic Alterations – Application of Epigenetics as Biomarkers

12.9 Potential Side Effects of Treatment with Epigenetic Drugs in Autoimmune Diseases

12.10 Balancing Conventional Therapy and Epigenetic Therapy

12.11 Where do we go from here?

12.12 Discussion

References

Chapter 13. Epigenetic Mechanisms of Human Imprinting Disorders

13.1 Introduction

13.2 Chromatin Structure Reflects Epigenetic Modifications

13.3 DNA Methylation and Transcriptional Silencing

13.4 Maintenance and Establishment of DNA Methylation During Development

13.5 Genomic Imprinting

13.6 Uniparental Disomy

13.7 Epimutations

13.8 Imprinting Center Mutations

13.9 Mutations in Imprinted Genes

13.10 Copy Number Abnormalities Encompassing Imprinted Genes

13.11 Mutations in Imprinting Establishment or Maintenance Machinery

13.12 Chromosome 6q24

13.13 Chromosome 7

13.14 Chromosome 11p15

13.15 Chromosome 14q32.2

13.16 Chromosome 15q11-q13

13.17 Chromosome 20q13.32

13.18 Hypomethylation at Multiple Imprinted Loci

13.19 Conclusion

References

Chapter 14. Epigenomic Factors in Human Obesity

14.1 Introduction

14.2 Epigenomic Marks

14.3 A Role for Imprinting Abnormalities in Obesity

14.4 Conflict Theory of Imprinting

14.5 Rare Imprinted Abnormalities with Obesity-Related Phenotypes

14.6 Dietary Influence on DNA Methylation in Murine Models

14.7 Obesogenic Environment Effects on Common Human Obesity

14.8 Aging Effect on DNA Methylation

14.9 Developmental Epigenomic Dysregulation

14.10 Fetal Plasticity

14.11 Postnatal Environmental Mismatch

14.12 Hypernutrition

14.13 Epigenetic Analysis of Leptin

14.14 Histone Epigenomic Modifiers – Master Metabolic Regulators

14.15 Metastable Alleles in Human Associated with Obesity

14.16 Parent-of-Origin Genetic Effects

14.17 Epigenomic-Wide Association Studies (EWAS) in Human Obesity

14.18 Future Prospects

References

Chapter 15. Epigenetic Approaches to Control Obesity

15.1 The Changing Epidemiology of Obesity

15.2 Developmental Origins of Obesity

15.3 Animal Studies of Early Development and Metabolic Programming

15.4 Developmental Plasticity

15.5 Epigenetics and Developmental Programming by the Early Life Environment

15.6 Epigenetics and Early-Life Nutrition

15.7 Identification of Predictive Epigenetic Markers of Future Obesity

15.8 Conclusions

References

Chapter 16. Epigenetics of Diabetes in Humans

16.1 Introduction

16.2 Epigenetic Mechanisms

16.3 Epigenetics, Insulin Secretion, and Diabetes

16.4 Epigenetics, Insulin Resistance, and Diabetes

16.5 Prospective

References

Chapter 17. The Potential of Epigenetic Compounds in Treating Diabetes

17.1 The Problem of Diabetes

17.2 Epigenetics

17.3 Aberrant Epigenetic Regulation of Gene Expression or Protein Function as a Cause of Diabetes

17.4 Aberrant Epigenetics within the Diabetic Setting

17.5 Non-Epigenetic Effects of Histone Modifier Proteins with Diabetes Pathogenesis

17.6 Potential for the Use of HDACi to Ameliorate or Treat Symptoms of Diabetes Pathogenesis

17.7 Conclusions

References

Chapter 18. Epigenetic Aberrations in Human Allergic Diseases

18.1 Introduction and Context: The Rising Prevalence of Allergic Diseases

18.2 Mechanisms of Allergic Response

18.3 Fetal life: The Critical Period of Immune Development

18.4 Developmental Differences in Gene Expression in Allergic Disease

18.5 Epigenetic Regulation of Immune Development

18.6 Factors that Modulate Allergic Disease Risk Through Epigenetic Mechanisms

18.7 Conclusions

References

Chapter 19. Therapy of Airway Disease: Epigenetic Potential

19.1 Introduction

19.2 Histone Acetylation and Inflammatory Gene Regulation

19.3 Acetylation of Non-histone Proteins

19.4 Corticosteroids Suppress Inflammation via Epigenetic Mechanisms

19.5 Molecular Mechanisms of Corticosteroid Resistance

19.6 Theophylline as an Epigenetic Modulator

19.7 Other Drugs

19.8 Future Directions

References

Chapter 20. The Role of Epigenetics in Cardiovascular Disease

20.1 Introduction

20.2 Epigenetics and EC Homeostasis

20.3 Epigenetics and SMC Homeostasis

20.4 Epigenetics and Atherosclerosis

20.5 Epigenetics and Heart Failure

20.6 Biomarker and MicroRNA

20.7 Summary and Future Perspectives

Acknowledgments

References

Chapter 21. Epigenetics and Human Infectious Diseases

21.1 Introduction

21.2 Epigenetic Modifications Elicited in Host Cells During Bacterial Infections

21.3 Virus-induced Epigenetic Alterations

21.4 Epigenetic Alterations Elicited in the Host Tissue by Trematode Infections

21.5 Conclusions

References

Chapter 22. The Epigenetics of Endometriosis

22.1 Introduction

22.2 Methods

22.3 All Roads Lead to Epigenetics

22.4 Evidence in Support that Endometriosis is an Epigenetic Disease

22.5 Histone Modifications in Endometriosis: An Unexplored Frontier

22.6 Epigenetic Aberration: Cause or Consequence?

22.7 Therapeutic Implications

22.8 Diagnostic and Prognostic Implications

22.9 Conclusions and Future Research Directions

Acknowledgment

References

Chapter 23. Aberrant DNA Methylation in Endometrial Cancer

23.1 Introduction

23.2 Epigenetic DNA Hypermethylation in Cancer Cells

23.3 Aberrant DNA Methylation in Endometrial Cancer

23.4 Methylation of microRNA in Endometrial Cancer

23.5 Application of Aberrant DNA Hypermethylation to Diagnostics

23.6 Application of Aberrant DNA Hypermethylation to Treatment

23.7 Future Directions and Conclusion

References

Chapter 24. Stem Cell Epigenetics and Human Disease

24.1 Introduction

24.2 Epigenetics

24.3 Stem Cell Epigenetics

24.4 Histone Variants and Exchange of Histones

24.5 Chromatin Bivalency in ESCs

24.6 Changing the Epigenetic Landscape During Cellular Reprogramming

24.7 Stem Cell Epigenetics and Human Disease

24.8 Modeling of Human Epigenetic Disorders Using iPSCs

24.9 Future Studies

References

Chapter 25. Non-Coding RNA Regulatory Networks, Epigenetics, and Programming Stem Cell Renewal and Differentiation: Implications for Stem Cell Therapy

25.1 Major Types of Stem Cells

25.2 A Brief Overview of Epigenetics

25.3 Epigenetic Programming of Stem Cells

25.4 Final Comments

References

Chapter 26. Aging and Disease: The Epigenetic Bridge

26.1 Introduction

26.2 Genes and Aging

26.3 The Dynamic Methylome

26.4 Epigenetic Dynamics in the Aging Brain

26.5 The Complexity of the Age-Associated Epigenetic Changes

26.6 Healthy and Pathological Aging

26.7 Environment, Epigenetics, and Aging

26.8 Epigenetics and Age-Associated Diseases

26.9 One Carbon Metabolism

26.10 One-carbon Metabolism in Aging and Neurodegeneration

26.11 Epigenetics and Neurodegeneration: The Alzheimer’s Disease Paradigm

26.12 Aged AD Mice and Epigenetics

26.13 Conclusion

References

Chapter 27. Early-Life Epigenetic Programming of Human Disease and Aging

27.1 Introduction

27.2 Intrauterine Growth Restriction

27.3 Fetal Macrosomia

27.4 Endocrine Programming During Intrauterine Development

27.5 Intrauterine Growth Restriction and Reprogramming of the Hypothalamic–Pituitary–Adrenal Axis

27.6 Early-life Programming of the Growth Hormone/Insulin-Like Growth Factors Axis

27.7 Early Interventions to Prevent and Treat Endocrine–Metabolic Disturbances

27.8 Early-Life Nutritional Programming of Adult Health and Aging

27.9 The Thrifty Phenotype and Thrifty Epigenotype Concepts

27.10 Prenatal Famine and Adult Health Outcomes

27.11 Effect of Prenatal Exposure to Methyl Donors on Developmental Programming

27.12 Long-Term Programming Effects of Prenatal Stress

27.13 Long-Term Impacts of Maternal Substance Use During Pregnancy

27.14 Programming Effect of Early-Life Exposure to Environmental Toxicants

27.15 Epigenetic Risks of Assisted Reproductive Technologies

27.16 Conclusions and Future Directions

References

Index

Color Plates

Quotes and reviews

"This volume constitutes a comprehensive survey of the emerging field of epigenetics in the etiology, progression, diagnosis, prognosis and treatment of human diseases… With its translational focus, this book will serve as valuable reference for both basic scientists and clinicians alike."--Anticancer Research, Volume 33, Issue no. 5, May 2013
"This book covers a huge range of topics, from early life effects on adult disease to epigenetic changes occurring with aging and senescence. Especially pertinent are the several chapters on epigenetic treatments for disease including drugs, miRNA/siRNA, natural substances and foods. With up to date coverage of an ever expanding field, Epigenetics in Human Disease will be a great resource for clinicians, researchers and students."--Craig Cooney, Investigator, Research Service, Veteran's Affairs Medical Center, Little Rock, AR & Affiliate Scientist, Nanotechnology Center, University of Arkansas, Little Rock, AR

 
 
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