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Epigenetics in Human Disease 2nd edition [Kõva köide]

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Edited by Trygve O. Tollefsbol (Distinguished Professor of Biology, University of Alabama at Birmingham, AL, USA)

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Formaat: Hardback, 1110 pages, kõrgus x laius: 235x191 mm, kaal: 2450 g
Sari: Translational Epigenetics
Ilmumisaeg: 18-May-2018
Kirjastus: Academic Press Inc
ISBN-10: 0128122153
ISBN-13: 9780128122150

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DNA & Genome

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Formaat: Hardback, 1110 pages, kõrgus x laius: 235x191 mm, kaal: 2450 g
Sari: Translational Epigenetics
Ilmumisaeg: 18-May-2018
Kirjastus: Academic Press Inc
ISBN-10: 0128122153
ISBN-13: 9780128122150

Teised raamatud teemal:

DNA & Genome

Püsilink: https://www.kriso.ee/db/9780128122150.html

Märksõnad:

Epigenetics in Human Disease, Second Edition examines the diseases and conditions on which we have advanced knowledge of epigenetic mechanisms, such as cancer, autoimmune disorders, aging, metabolic disorders, neurobiological disorders and cardiovascular disease. In addition to detailing the role of epigenetics in the etiology, progression, diagnosis and prognosis of these diseases, novel epigenetic approaches to treatment are also explored. Fully revised and up-to-date, this new edition discusses topics of current interest in epigenetic research, including stem cell epigenetic therapy, bioinformatic analysis of NGS data, and epigenetic mechanisms of imprinting disorders.

Further sections explore online epigenetic tools and datasets, early-life programming of epigenetics in age-related diseases, the epigenetics of addiction and suicide, and epigenetic approaches to regulating and preventing diabetes, cardiac disease, allergic disorders, Alzheimer’s disease, respiratory diseases, and many other human maladies.

Includes contributions from leading international investigators involved in translational epigenetic research and therapeutic applications
Integrates methods and applications with fundamental chapters on epigenetics in human disease, along with an evaluation of recent clinical breakthroughs
Presents side-by-side coverage of the basis of epigenetic diseases and treatment pathways
Provides a fully revised resource covering current developments, including stem cell epigenetic therapy, the bioinformatic analysis of NGS data, epigenetic mechanisms of imprinting disorders, online epigenetic tools and datasets, and more

List of Contributors

xxix

Preface

xxxv

SECTION I INTRODUCTION

Chapter 1 Epigenetics of Human Disease

(10)

Trygve O. Tollefsbol

1.1 Introduction

(1)

1.2 Methodology

(1)

1.3 Human Cancer

(1)

1.4 Neurological Disease

(1)

1.5 Autoimmunity and Epigenetics

(1)

1.6 Metabolic Disorders

(1)

1.7 Other Disorders/Diseases

(1)

1.8 Development, Aging, and Transgenerational Effects

(1)

1.9 Future Research

(1)

1.10 Conclusion

(4)

References

(4)

SECTION II METHODOLOGY

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

(26)

Yoshihisa Watanabe

Masato Maekawa

2.1 Introduction

(1)

2.2 DNA Methylation Analysis

(4)

2.2.1 Methylation-Sensitive Restriction Enzymes

(1)

2.2.2 Bisulfite Conversion of Unmethylated Cytosines, PCR, and Sequencing

(1)

2.2.3 Comparative Genomic Hybridization and Microarray Analysis

(1)

2.2.4 Bisulfite Treatment and PCR-Based Single-Strand Conformation Polymorphism

(1)

2.2.5 Methylation-Sensitive Single-Nucleotide Primer Extension

(1)

2.2.6 Combined Bisulfite and Restriction Analysis

(1)

2.2.7 Quantitative Bisulfite Sequencing Using Pyrosequencing Technology; DNA Methylation Analysis by Pyrosequencing

(1)

2.2.8 Methylation-Specific PCR

(1)

2.2.9 MethyLight Technology

(1)

2.2.10 Quantitative Analysis of Methylated Alleles

(1)

2.2.11 Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry

(1)

2.2.12 Other Technologies

(1)

2.2.13 Computational Tools

(1)

2.3 Histone Modification Analysis

(1)

2.4 Noncoding RNA Analysis: MicroRNA

(2)

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

(2)

2.6 Strategy for Epigenomic Investigation Based on Chromosomal Band Structures

(3)

2.7 Recent Developments in Genome-Wide and Bioinformatic Analyses of the Epigenome

(4)

2.8 Relationships Between Neuronal Plasticity and Neural Disease, and Chromosomal R/G Band Boundaries

(1)

2.9 General Overview and Future Perspectives

(8)

Glossary

(1)

Acknowledgments

(1)

References

(7)

Chapter 3 DNA Methylation---Based Measures of Biological Aging

(26)

Pierre-Antoine Dugue

Shuai Li

John L. Hopper

Roger L. Milne

3.1 Introduction

(1)

3.1.1 Aging and DNA Methylation

(1)

3.1.2 DNA Methylation---Based Measures of Biological Age

(1)

3.2 Measuring Age Acceleration

(5)

3.2.1 Regularized Regression Methodology

(3)

3.2.2 DNA Methylation---Based Biological Aging Measures

(1)

3.2.3 Tissues and Blood Cell Composition

(1)

3.3 Age Acceleration, Mortality, and Disease

(3)

3.3.1 Mortality

(1)

3.3.2 Cancer

(1)

3.3.3 Other Diseases

(1)

3.4 Determinants of Age Acceleration

(5)

3.4.1 Sex and Ethnicity

(1)

3.4.2 Early Life Factors

(1)

3.4.3 Evidence for Lifestyle and Environmental Determinants

(3)

3.4.4 Evidence for Genetic Determinants

(1)

3.5 Other Aspects of the Aging Methylome

(2)

3.5.1 Epigenetic Drift, Mitotic Clock, and Individual CpG Sites

(1)

3.5.2 Comparison With Telomere Length

(1)

3.6 Conclusion

(9)

Acknowledgment

(1)

References

(8)

Chapter 4 Bioinformatics of Epigenomic Data Generated From Next-Generation Sequencing

(44)

Fei-Man Hsu

Moloya Gohain

Pearl Chang

Jui-Hsien Lu

Pao-Yang Chen

4.1 Introduction

(2)

4.2 Preprocessing Data From Next-Generation Sequencing

(1)

4.3 Read Alignment

(2)

4.4 Profiling DNA Methylation

(6)

4.4.1 DNA Methylation

(1)

4.4.2 Experimental Approaches

(1)

4.4.3 Methylome

(1)

4.4.4 BS-Seq Data Analysis

(2)

4.4.5 Profiling 5-Hydroxymethylation

(1)

4.4.6 Quality Assessment of BS-Seq

(1)

4.4.7 Application of BS-Seq in Cancer Research

(1)

4.4.8 Conclusion

(1)

4.5 Assessing DNA---Protein Interaction in the Chromatin-ChIP-Seq

(5)

4.5.1 Preparing ChIP-Seq Sequencing Samples

(2)

4.5.2 Identifying DNA Sequences Associated With Proteins or Histone Modifications

(1)

4.5.3 Quality Assessment of ChIP-Seq Data

(1)

4.5.4 ChIP-Seq in Cancer Research

(1)

4.5.5 Conclusion

(1)

4.6 Analysis of the Small RNA Component of the Epigenome

(4)

4.6.1 Biogenesis of Small RNA Classes

(1)

4.6.2 Next-Generation Sequencing of Small RNA

(1)

4.6.3 Profiling Micro RNAs

(1)

4.6.4 Quality Assessment of sRNA-Seq Data

(1)

4.6.5 Prediction of Micro RNA in the Genome

(1)

4.6.6 Predicting Micro RNA Targets

(1)

4.6.7 Application of miRNA-Seq in Cancer Research

(1)

4.6.8 Conclusion

(1)

4.7 Profiling Chromatin Accessibility Using ATAC-Seq

(5)

4.7.1 Investigating Chromatin Accessibility

(1)

4.7.2 Preparing ATAC-Seq Samples

(1)

4.7.3 Determining Open Chromatin Regions Using ATAC-Seq

(1)

4.7.4 Quality Assessment of ATAC-Seq Data

(2)

4.7.5 Application of ATAC-Seq in Cancer Research

(1)

4.7.6 Conclusion

(1)

4.8 Chromosome Conformation Capture

(1)

4.9 Integration of Epigenome Data

(1)

4.10 Predicting Transcriptional Factor Binding Sites With Epigenomics Data

(1)

4.10.1 Epigenomic Regulation

(1)

4.10.2 Hit-Based Transcription Factor Binding Site Prediction

(1)

4.10.3 Site-Centric Transcription Factor Binding Site Prediction

(1)

4.10.4 Segmentation-Based Transcription Factor Binding Site Prediction

(1)

4.11 Case Studies of Epigenetics in Assisted Reproductive Technology

(3)

4.11.1 In Vitro Fertilization-Associated Transcriptomic Changes

(1)

4.11.2 In Vitro Fertilization-Associated DNA Methylation Changes at Imprinted Loci

(1)

4.11.3 In Vitro Fertilization-Associated DNA Methylation at Infertility Genes

(1)

4.11.4 Other ART-Associated Epigenomic Changes

(1)

4.12 Summary

(13)

List of Abbreviations

(1)

Acknowledgments

(1)

References

(11)

SECTION III HUMAN CANCER

Chapter 5 DNA Methylation Alterations in Human Cancers

109

(32)

Sumei Wang

Wanyin Wu

5.1 Introduction of DNA Methylation

110

(8)

5.1.1 DNA Methytransferase

110

(3)

5.1.2 CpG Dinucleotide/CpG Island

113

(1)

5.1.3 Methyl-CpG Binding Proteins

114

(1)

5.1.4 Methods Detecting DNA Methylation

114

(4)

5.2 Characteristics of the DNA Methylation in Human Cancers

118

(3)

5.2.1 DNA Methyltransferases and Human Cancer

118

(1)

5.2.2 DNA Methylation and Genome Instability in Human Cancers

119

(1)

5.2.3 Gene Promoter DNA Methylation in Human Cancers

120

(1)

5.2.4 Gene Body Methylation in Human Cancers

121

(1)

5.3 Functional Roles/Consequences of DNA Methylation in Human Cancers

121

(4)

5.3.1 DNA Methylation Alterations in the Initiation and Development of Human Cancers

122

(1)

5.3.2 DNA Methylation Alterations in the Metastasis of Human Cancers

123

(1)

5.3.3 DNA Methylation---Related Signaling Pathway Alterations in Human Cancers

124

(1)

5.3.4 Regulation Between DNA Methylation and Noncoding RNAs in Human Cancers

124

(1)

5.4 Clinical Applications of DNA Methylation in Tumor Diagnosis and Therapy

125

(16)

5.4.1 Role of DNA Methylation in Human Cancer Diagnosis

125

(1)

5.4.2 Role of DNA Methylation in Human Cancer Therapy

126

(1)

5.4.3 Future Direction and Potential Pitfalls of DNA Methylation in Human Cancers

127

(1)

List of Acronyms and Abbreviations

128

(3)

References

131

(10)

Chapter 6 Alterations of Histone Modifications in Cancer

141

(78)

Amir Hosseini

Saverio Minucci

6.1 Introduction

142

(1)

6.2 Chromatin Organization

142

(2)

6.3 Histone Modifications

144

(15)

6.3.1 Histone Acetylation

145

(3)

6.3.2 Histone Methylation

148

(5)

6.3.3 Histone Phosphorylation

153

(2)

6.3.4 Histone Ubiquitination

155

(1)

6.3.5 Mode of Action of Histone Modifications

156

(2)

6.3.6 Histone Cross Talk

158

(1)

6.4 Histone Modifications and Cancer

159

(6)

6.4.1 Alterations in the Pattern of Histone H4 Modifications

159

(3)

6.4.2 Alterations in the Pattern of Histone H3 Modifications

162

(3)

6.5 Mechanisms Underlying Alterations of Histone Modifications in Cancer

165

(20)

6.5.1 Alteration of the Histone Acetylation Network (HATs, HDACs, and Sirtuins)

165

(8)

6.5.2 Alteration of the Histone Methylation Network (HMTs, PRMTs, and HDMs)

173

(10)

6.5.3 Alterations of Histone Kinases, Histone Ubiquitinating, and Deubiquitinating Enzymes

183

(1)

6.5.4 Other Mechanisms

184

(1)

6.6 Conclusions

185

(34)

Glossary and Abbreviations

187

(2)

References

189

(30)

Chapter 7 Epigenetic Approaches to Cancer Therapy

219

(32)

Sabita N. Saldanha

Trygve O. Tollefsbol

7.1 Introduction

219

(2)

7.2 DNA Methylation

221

(1)

7.3 Histone Modifications

221

(10)

7.3.1 Histone Acetylation and Deacetylation

221

(9)

7.3.2 Histone Methylation

230

(1)

7.4 Nonhistone Protein Modifications

231

(5)

7.4.1 Acetylation

231

(2)

7.4.2 Methylation

233

(1)

7.4.3 Phosphorylation

234

(1)

7.4.4 SUMOylation

234

(1)

7.4.5 Ubiquitination

235

(1)

7.5 miRNAs

236

(3)

7.6 Long Noncoding RNAs

239

(1)

7.7 Exosomes

239

(2)

7.8 Future Directions

241

(10)

References

241

(10)

SECTION IV NEUROLOGICAL DISEASE

Chapter 8 Epigenetics in Neurobehavioral Disease

251

(18)

Jannet Kocerha

Neha Aggarwal

8.1 Introduction

251

(2)

8.2 Noncoding RNAs

253

(2)

8.2.1 MicroRNAs

253

(1)

8.2.2 Long Noncoding RNAs

254

(1)

8.2.3 Circular RNAs

254

(1)

8.2.4 Natural Antisense Transcripts

255

(1)

8.3 Chromatin Stability and Modifications of DNA and Histones

255

(1)

8.4 Neurotransmitters

256

(1)

8.5 Neurogenesis

256

(1)

8.6 Mood-Based Disorders

257

(1)

8.7 Addiction

258

(1)

8.8 Psychotic Disorders

259

(1)

8.9 Anxiety, Fear, and Stress Disorders

260

(1)

8.10 Sleep and Circadian Rhythm Disorders

261

(1)

8.11 Conclusion

262

(7)

References

262

(7)

Chapter 9 Emerging Role of Epigenetics in Human Neurodevelopmental Disorders

269

(36)

Giuseppina Mastrototaro

Alessandro Sessa

9.1 Identification Techniques of Genes Associated With Neurodevelopmental Disorders: A Historical Overview

270

(1)

9.2 Epigenetics in Neurodevelopmental Disorders

270

(1)

9.3 DNA Methylation

271

(3)

9.4 Histone Posttranslational Modifications

274

(9)

9.4.1 Aberration in Histone Tail Methylation

276

(4)

9.4.2 Aberration in Histone Tail Acetylation

280

(2)

9.4.3 Aberration in Histone Tail Phosphorylation

282

(1)

9.5 ATP-Dependent Chromatin Remodeling Proteins

283

(3)

9.6 Noncoding RNAs in Neurodevelopmental Disorders

286

(3)

9.6.1 MicroRNAs

286

(1)

9.6.2 Long Noncoding RNA

287

(2)

9.7 Epigenetic Therapy

289

(6)

9.8 Conclusions and Remarks

295

(10)

References

296

(9)

Chapter 10 The Epigenetics of Alzheimer's and Other Neurodegenerative Disorders

305

(22)

Fabio Coppede

10.1 Introduction: Epigenetics and Neurodegenerative Diseases

306

(1)

10.2 A Brief Overview of Epigenetic Mechanisms

306

(1)

10.2.1 DNA Methylation and Hydroxymethylation

306

(1)

10.2.2 Histone Tail Modifications

306

(1)

10.2.3 Mechanisms Mediated by Non-coding RNAs

307

(1)

10.3 DNA Methylation and Histone Tail Modifications in Alzheimer's Disease

307

(4)

10.3.1 DNA Methylation in Alzheimer's Disease

308

(3)

10.3.2 Histone Tail Modifications in Alzheimer's Disease

311

(1)

10.4 DNA Methylation and Histone Tail Modifications in Parkinson's Disease

311

(2)

10.4.1 DNA Methylation in Parkinson's Disease

312

(1)

10.4.2 Histone Tail Modifications in Parkinson's Disease

312

(1)

10.5 DNA Methylation and Histone Tail Modifications in Amyotrophic Lateral Sclerosis

313

(2)

10.5.1 DNA Methylation in Amyotrophic Lateral Sclerosis

314

(1)

10.5.2 Histone Tail Modifications in Amyotrophic Lateral Sclerosis

314

(1)

10.6 DNA Methylation and Histone Tail Modifications in Huntington's Disease

315

(1)

10.6.1 DNA Methylation in Huntington's Disease

315

(1)

10.6.2 Histone Tail Modifications in Huntington's Disease

315

(1)

10.7 Mitoepigenetics and Neurodegenerative Diseases

316

(1)

10.8 Non-coding RNAs and Neurodegenerative Diseases

316

(1)

10.9 Conclusion

317

(10)

List of Acronyms and Abbreviations

319

(1)

Glossary

320

(1)

References

321

(6)

Chapter 11 Epigenetic Modulation of Human Neurobiological Disorders

327

(26)

Khue Vu Nguyen

11.1 Introduction

327

(1)

11.2 Epigenetic Regulation Overview

328

(10)

11.2.1 DNA Methylation, Histone Modification, and RNA Transcripts

328

(3)

11.2.2 Alternative Splicing

331

(2)

11.2.3 Genomic Rearrangements

333

(5)

11.3 Epigenetic Modifications in Human Neurobiological Disorders

338

(2)

11.3.1 Current Epigenetic Diagnosis

338

(1)

11.3.2 Current Epigenetic Therapies

339

(1)

11.4 Future Directions

340

(13)

List of Abbreviations

342

(2)

References

344

(9)

SECTION V AUTOIMMUNE DISEASE

Chapter 12 Epigenetic Basis of Autoimmune Disorders in Humans

353

(34)

Yasuto Araki

Toshihide Mimura

12.1 Introduction

354

(1)

12.2 The Pathogenesis of Autoimmune Diseases

354

(4)

12.2.1 Autoreactive Lymphocytes and Autoantibodies

354

(1)

12.2.2 Immunological Self-Tolerance

355

(1)

12.2.3 Genetic, Environmental, and Epigenetic Factors in Autoimmune Diseases

356

(2)

12.3 Epigenetic Regulation of Gene Transcription

358

(2)

12.3.1 DNA Methylation

358

(1)

12.3.2 Histone Modifications

359

(1)

12.3.3 MicroRNAs

359

(1)

12.4 Disordered Epigenetic Mechanisms in Rheumatoid Arthritis

360

(4)

12.4.1 Disordered DNA Methylation in Rheumatoid Arthritis

360

(1)

12.4.2 Disordered Histone Modifications in Rheumatoid Arthritis

361

(2)

12.4.3 Disordered MicroRNA Expression in Rheumatoid Arthritis

363

(1)

12.5 Disordered Epigenetic Mechanisms in Systemic Lupus Erythematosus

364

(3)

12.5.1 Disordered DNA Methylation in Systemic Lupus Erythematosus

364

(2)

12.5.2 Disordered Histone Modifications in Systemic Lupus Erythematosus

366

(1)

12.5.3 Disordered MicroRNA Expression in Systemic Lupus Erythematosus

366

(1)

12.6 Disordered Epigenetic Mechanisms in Systemic Sclerosis

367

(2)

12.6.1 Disordered DNA Methylation in Systemic Sclerosis

367

(1)

12.6.2 Disordered Histone Modifications in Systemic Sclerosis

368

(1)

12.6.3 Disordered MicroRNA Expression in Systemic Sclerosis

369

(1)

12.7 Disordered Epigenetic Mechanisms in Primary Biliary Cholangitis or Cirrhosis

369

(1)

12.7.1 Disordered DNA Methylation in Primary Biliary Cholangitis or Cirrhosis

369

(1)

12.7.2 Disordered Histone Modifications in Primary Biliary Cholangitis or Cirrhosis

369

(1)

12.7.3 Disordered MicroRNA Expression in Primary Biliary Cholangitis or Cirrhosis

370

(1)

12.8 Disordered Epigenetic Mechanisms in Type 1 Diabetes

370

(2)

12.8.1 Disordered DNA Methylation in Type 1 Diabetes

370

(1)

12.8.2 Disordered Histone Modifications in Type 1 Diabetes

371

(1)

12.8.3 Disordered MicroRNA Expression in Type 1 Diabetes

371

(1)

12.9 Conclusion

372

(15)

Glossary

372

(4)

References

376

(11)

Chapter 13 Approaches to Autoimmune Diseases Using Epigenetic Therapy

387

(22)

Christian M. Hedrich

13.1 Introduction

387

(1)

13.2 DNA Methylation and DNA Hydroxymethylation

388

(3)

13.3 Histone Modifications

391

(3)

13.4 Noncoding RNAs

394

(3)

13.5 Influencing Epigenetic Patterns Through Behavior

397

(1)

13.6 Potential Future Interventions

397

(1)

13.7 Conclusions

398

(11)

List of Abbreviations

398

(1)

References

399

(10)

SECTION VI METABOLIC DISORDERS

Chapter 14 Epigenomics and Human Obesity

409

(18)

Cathrine Hoyo

David A. Skaar

Sarah S. Park

Patricia Sorrow

14.1 Introduction

409

(2)

14.2 DNA Methylation and Human Obesity

411

(1)

14.3 DNA Methylation Regulating Genomic Imprinting

411

(2)

14.4 DNA Methylation Regulating Metastable Epialleles

413

(1)

14.5 Genome-Scale CpG Methylation Approaches and Human Obesity

413

(4)

14.5.1 Genome-Scale CpG Methylation and Obesity in Adults

414

(2)

14.5.2 Genome-Scale CpG Methylation and Obesity in Children

416

(1)

14.6 CpG Methylation and an Established Obesity Risk Factor

417

(1)

14.7 Race/Ethnic Differences in CpG Methylation and Obesity

418

(1)

14.8 Sex Differences in CpG Methylation and Obesity

418

(1)

14.9 The Future

418

(9)

References

419

(8)

Chapter 15 Early-Life Nutrition, Epigenetics and Prevention of Obesity

427

(30)

Sarah El-Heis

Karen A. Lillycrop

Graham C. Burdge

Peter D. Gluckman

Mark A. Hanson

Keith M. Godfrey

15.1 The Changing Epidemiology of Obesity

427

(1)

15.2 Developmental Origins of Obesity

428

(3)

15.3 Animal Studies of Early Development and Metabolic Programming

431

(4)

15.3.1 The Maternal Protein-Restricted Diet

431

(2)

15.3.2 Global Dietary Restriction

433

(1)

15.3.3 High-Fat Diet During Pregnancy and Early Postnatal Life

434

(1)

15.4 Developmental Plasticity

435

(1)

15.5 Epigenetics and Developmental Programming by the Early-Life Environment

436

(3)

15.6 Epigenetics and Maternal 1-Carbon Nutrients

439

(1)

15.7 Transgenerational Effects

439

(1)

15.8 Mechanism of Epigenetic Change

440

(2)

15.9 Human Studies of Maternal Nutrition and Epigenetic Alterations

442

(1)

15.10 Identification of Predictive Epigenetic Markers of Future Obesity

442

(4)

15.11 Conclusions

446

(11)

List of Acronyms and Abbreviations

447

(1)

References

447

(10)

Chapter 16 Epigenetics of Diabetes in Humans

457

(32)

Jana Nano

Eliana Portilla Fernandez

Jenna Troup

Mohsen Ghanbari

Oscar H. Franco

Taulant Muka

16.1 Introduction

457

(3)

16.2 Global DNA Methylation, Type 2 Diabetes, and Glycemic Traits

460

(1)

16.3 Candidate Gene Studies of DNA Methylation, Type 2 Diabetes, and Glycemic Traits

461

(2)

16.4 Epigenome-Wide Analysis, Type 2 Diabetes, and Glycemic Traits

463

(1)

16.5 Histone Modifications and Type 2 Diabetes

463

(13)

16.6 Epidemiological Considerations of the Studies

476

(2)

16.6.1 Tissue

476

(1)

16.6.2 Epigenetic Technology

476

(1)

16.6.3 Confounding and Study Designs

476

(1)

16.6.4 Causality

477

(1)

16.7 Transgenerational Epigenetics

478

(1)

16.8 Clinical Implications

478

(3)

16.8.1 Epigenetic Modifications as Biomarkers for Risk Stratification and Disease Diagnosis

478

(1)

16.8.2 Diabetic Complications: Metabolic Memory and Epigenetics

479

(1)

16.8.3 Role of Epigenetic Marks in Disease Prevention

480

(1)

16.8.4 Epigenetics Marks as Potential Drug Targets in Diabetes

481

(1)

16.9 Perspectives and Conclusion

481

(8)

References

482

(7)

Chapter 17 The Potential of Epigenetic Compounds in Treating Diabetes

489

(62)

Steven G. Gray

17.1 Diabetes Is a Significant Problem

491

(1)

17.2 Epigenetics

491

(5)

17.2.1 DNA CpG Methylation

491

(1)

17.2.2 Histone Posttranslational Modifications

492

(1)

17.2.3 Histone Variants

493

(1)

17.2.4 Noncoding RNA

494

(2)

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

496

(3)

17.3.1 Aberrant Epigenetics Within the Diabetic Setting

496

(3)

17.4 Histone Deacetylases

499

(5)

17.4.1 Would the Real HDAC Please Stand up?

499

(5)

17.5 Effects of Histone Deacetylase Inhibitor on Diabetogene Expression

504

(4)

17.5.1 Class I---Hormones

505

(1)

17.5.2 Class II---Transcription Factors

506

(1)

17.5.3 Class III---Transporters

507

(1)

17.6 Aberrant MicroRNAs/Epi-microRNAs and Diabetes

508

(2)

17.6.1 Effects of Epigenetic Inhibitors on MicroRNAs

509

(1)

17.7 Nonepigenetic Effects of Histone Modifier Proteins With Diabetes Pathogenesis

510

(2)

17.7.1 Inflammation in Diabetes Pathogenesis

510

(1)

17.7.2 Endoplasmic Reticulum Stress/Chaperones and Diabetes Pathogenesis

511

(1)

17.8 Potential for the Use of Epigenetic Targeting Agents to Ameliorate or Treat Symptoms of Diabetes Pathogenesis

512

(3)

17.8.1 Bromodomain and Extra-Terminal Bromodomain Inhibitors

512

(1)

17.8.2 Lysine Acetyltransferase Inhibitors

513

(1)

17.8.3 Lysine Demethylase Inhibitors

513

(1)

17.8.4 Histone Deacetylase Inhibitors

513

(1)

17.8.5 Pancreatic Islet Development and Protection Using Histone Deacetylase Inhibitors

513

(1)

17.8.6 Modulation of Th1/Th17-Mediated Autoimmunity

514

(1)

17.8.7 Stem Cells

514

(1)

17.8.8 The Ability of Certain Histone Deacetylase Inhibitor to Act as Chaperones and Alleviate Endoplasmic Reticulum Stress

515

(1)

17.9 Histone Deacetylase Inhibitor Specificity---Is This an Issue?

515

(1)

17.10 Nutrition-Based Natural Compounds as Therapeutic Agents

516

(6)

17.10.1 Sulforaphane

516

(1)

17.10.2 Butyrates

517

(1)

17.10.3 Curcumin

517

(1)

17.10.4 Epigallocatechin 3-Gallate

518

(1)

17.10.5 Honokiol

518

(1)

17.10.6 Resveratrol

518

(1)

17.10.7 Other Nutritionals

519

(2)

17.10.8 miRNA/siRNA-Based Therapeutics?

521

(1)

17.11 Conclusions

522

(29)

References

522

(29)

SECTION VII OTHER DISODERS/DISEASES

Chapter 18 Epigenetic-Processes Driven Disorders and Therapeutics

551

(22)

Sravya Thumoju

Vasavi Mohan

18.1 What Is Epigenetics?

551

(1)

18.2 Introduction

552

(3)

18.2.1 DNA Methylation

552

(1)

18.2.2 Histone Modifications

553

(1)

18.2.3 RNA-Associated Silencing

554

(1)

18.3 Epigenetics and Environment

555

(2)

18.3.1 Nutrition and Metabolomics

555

(1)

18.3.2 During Development

556

(1)

18.3.3 Microbiome

557

(1)

18.3.4 Pollutants

557

(1)

18.4 Epigenetics in Human Diseases

557

(10)

18.4.1 Cardiovascular Diseases

557

(1)

18.4.2 In Cancer

558

(2)

18.4.3 Imprinting Disorders

560

(2)

18.4.4 Pediatric Disorders

562

(1)

18.4.5 Immunity

562

(2)

18.4.6 Neuropsychiatric/Neurodevelopmental Disorders

564

(2)

18.4.7 Aging

566

(1)

18.5 Conclusion

567

(6)

References

568

(4)

Further Reading

572

(1)

Chapter 19 Epigenetics of Allergic Diseases Allergies, Eczema, Asthma, and Rhinitis

573

(34)

Wilfried Karmaus

Ali H. Ziyab

Nandini Mukherjee

19.1 Prevalence of Allergic Diseases

573

(1)

19.2 Plasticity of Allergic Diseases

574

(1)

19.3 Time Order and the Concept of the Developmental Origins of Health and Disease

574

(2)

19.4 Allergy and Atopy

576

(1)

19.5 Eczema

577

(1)

19.6 Asthma

578

(1)

19.7 Food Allergies

578

(1)

19.8 Allergic Rhinitis

579

(1)

19.9 Epigenetics

579

(1)

19.10 Epigenetic Changes and Changes in Cell Composition

580

(1)

19.11 Epigenetics Related to Atopy and Immunoglobulin Levels

581

(1)

19.12 Epigenetics of Eczema

581

(6)

19.13 Epigenetics of Food Allergies

587

(1)

19.14 Epigenetics of Asthma

588

(5)

19.15 Epigenetics Related to Allergic Rhinitis

593

(1)

19.16 Putting It all Together

594

(13)

Glossary

595

(1)

References

595

(12)

Chapter 20 Epigenetic Treatment Approaches to Cardiovascular Disease

607

(36)

Asish K. Ghosh

Douglas E. Vaughan

20.1 Introduction

608

(1)

20.2 Epigenetic Treatment Approaches Targeting MicroRNAs

609

(6)

20.2.1 MicroRNA Mimics and Antagomir as Epidrugs for Hypertension, Cardiomyopathy, and Myocardial Infarction

609

(5)

20.2.2 Antagomir and MicroRNA Mimics as Epidrugs for Atrial Fibrillation

614

(1)

20.3 Epigenetic Treatment Approaches Targeting Histone Deacetylases (Erasers)

615

(5)

20.3.1 HDACi as Epidrugs for Hypertension-Associated Cardiovascular Diseases

615

(1)

20.3.2 HDACi as Epidrugs for Myocardial Infarction

616

(1)

20.3.3 HDACi as Epidrugs for Atrial and Ventricular Fibrillation

617

(1)

20.3.4 HDACi as Epidrugs for Atherosclerosis

618

(1)

20.3.5 HDACi as Epidrugs for Cardiomyopathy

619

(1)

20.4 Epigenetic Treatment Approaches Targeting Histone Acetyltransferases (Writers) and BET Proteins (Readers)

620

(5)

20.4.1 p300i as Epidrugs for Hypertension and Myocardial Infarction

621

(2)

20.4.2 p300i as Epidrugs for Diabetic- and Obesity-Associated Cardiomyopathy

623

(1)

20.4.3 BETi as Epidrugs for Hypertension and Myocardial Infarction

624

(1)

20.5 Epigenetic Treatment Approaches Targeting Methyltransferases

625

(5)

20.5.1 DNMTi as Epidrugs for Hypertension and Myocardial Infarction

625

(2)

20.5.2 DNMTi as Epidrugs for Atherosclerosis, Atrial Fibrillation, and Arteriosclerosis

627

(1)

20.5.3 HMTi as Epidrugs for Hypertension-Associated Cardiovascular Diseases

628

(2)

20.6 Future Promise and Challenges of Epidrug Therapy for Cardiovascular Diseases

630

(13)

Glossary

631

(1)

Acknowledgments

632

(1)

References

633

(10)

Chapter 21 Epigenetics and Human Infectious Diseases

643

(46)

Hans Helmut Niller

Janos Minarovits

21.1 Introduction

644

(1)

21.2 Epigenetic Modifications Elicited in Host Cells During Bacterial Infections

645

(13)

21.2.1 Epigenetic Alterations Induced by Bacterial Infections in Periodontal Disease

645

(1)

21.2.2 Histone Modifications Caused by Listeria monocytogenes

646

(1)

21.2.3 Histone Dephosphorylation by OspF, the Effector Protein of Shigella flexneri

647

(1)

21.2.4 Histone and DNA Modifications in Anaplasma phagocytophilum---Infected Cells

647

(1)

21.2.5 Epigenetic Alterations Associated With Helicobacter pylori Infection

648

(3)

21.2.6 Uropathogenic Escherichia coli Infection Downregulates CDKN2A (p16INK4A)

651

(1)

21.2.7 Chlamydophila spp.---Encoded Histone Methyltransferases: Putative Inducers of Epigenetic Reprogramming in Host Cell Nuclei

651

(2)

21.2.8 Reprogramming of the Host Cell Transcription by Epigenetic Regulators of Ehrlichia chaffeensis, Bordetella bronchiseptica, Burkholderia thailandensis, and Legionella pneumophila

653

(1)

21.2.9 Alteration of the Host Cell Methylome by Mycoplasma hyorhinis---Encoded DNA Methyltransferases

654

(1)

21.2.10 Epigenetic Dysregulation Elicited by Secreted Proteins of Mycobacterium tuberculosis

655

(2)

21.2.11 Alteration of the Histone Acetylation "Landscape" in Host Cell Chromatin by Intracellular Mycobacterium tuberculosis Infection

657

(1)

21.2.12 Induction of Epigenetic Alterations and Epithelial---Mesenchymal Transition by Mycobacterium leprae

657

(1)

21.3 Virus-Induced Epigenetic Alterations

658

(13)

21.3.1 Epigenetic Alterations in Cells Carrying Latent Gammaherpesvirus Genomes

658

(4)

21.3.2 Interactions of Lytic Cycle Proteins of Human Cytomegalovirus With Histone Deacetylases

662

(1)

21.3.3 Epigenetic Dysregulation in Human Retrovirus---Infected Cells

663

(2)

21.3.4 Local Hypermethylation and Global Hypomethylation of the Host Cell DNA in Hepatocellular Carcinomas Associated With Hepatitis B Virus

665

(2)

21.3.5 Hepatitis C Virus---Induced Epigenetic Alterations

667

(2)

21.3.6 Induction of DNA Methyltransferase, Histone Methyltransferase and Histone Demethylase Enzymes by the Human Papillomavirus Oncoprotein E7

669

(1)

21.3.7 Epigenetic Transcriptional Silencing in Merkel Cell Polyomavirus---Associated Carcinoma of the Skin

670

(1)

21.4 Epigenetic Alterations Elicited in the Host Tissue by Trematode Infections

671

(1)

21.4.1 Promoter Hypermethylation in Cholangiocarcinoma Associated With Opisthorchis viverrini (Liver Fluke) Infection

671

(1)

21.4.2 CpG Island Methylation in Schistosoma haematobium---Associated Bladder Carcinoma

671

(1)

21.5 Conclusions

672

(17)

Acknowledgments

672

(1)

References

672

(17)

Chapter 22 Therapy of Infectious Diseases Using Epigenetic Approaches

689

(28)

Zhigang Zhou

Sheeja Rajasingh

Bahar Barani

Saheli Samanta

Buddhadeb Dawn

Ruilan Wang

Johnson Rajasingh

22.1 Introduction

690

(1)

22.2 Epigenetic Modifications

690

(8)

22.2.1 DNA Modifications

691

(1)

22.2.2 Histone Modifications

692

(4)

22.2.3 Noncoding RNAs

696

(2)

22.3 Epigenetic Regulations and Infection

698

(4)

22.3.1 Innate Immune Response

700

(1)

22.3.2 Adaptive Immune Response

701

(1)

22.4 Epigenetic Drugs and Their Applications During Infection

702

(3)

22.4.1 DNA Methylating Agents

702

(1)

22.4.2 Histone Deacetylation Inhibitors

703

(2)

22.4.3 Toxicity of Epigenetic Drugs

705

(1)

22.5 Future Perspective of Epigenetic Modifiers in Clinical Treatment

705

(1)

22.6 Conclusion

706

(11)

List of Abbreviations

706

(2)

Acknowledgments

708

(1)

References

708

(9)

Chapter 23 Translational Aspects of the Endometriosis Epigenome

717

(34)

Mariano Colon-Caraballo

Idhaliz Flores-Caldera

23.1 Introduction

718

(4)

23.1.1 Endometriosis

718

(3)

23.1.2 Endometrium

721

(1)

23.2 Epigenetics of Endometriosis

722

(12)

23.2.1 DNA Methylation in Endometriosis and Endometrium

723

(6)

23.2.2 Histone Modifications in Endometriosis and Endometrium

729

(4)

23.2.3 miRNAs in Endometriosis and Endometrium

733

(1)

23.3 Translational Aspects of the Endometriosis Epigenome

734

(5)

23.3.1 The Endometriosis Epigenome as Therapeutic Target

734

(4)

23.3.2 The Epigenome as Diagnostic Target for Endometriosis

738

(1)

23.4 Summary

739

(12)

List of Acronyms and Abbreviations

740

(1)

References

741

(10)

Chapter 24 Aberrant DNA Methylation Patterns in Gynecologic Cancers: Implications for Prevention and Therapy

751

(30)

Megan Beetch

Yunfeng Bai

Katarzyna Lubecka

Barbara Stefanska

Sophie A. Lelievre

24.1 Introduction

751

(5)

24.1.1 DNA Methylation as a Cornerstone of Sustained Modifications Driving Cancer Behavior

752

(2)

24.1.2 DNA Methylation Occurs in a Context of Higher Order Chromatin Organization

754

(2)

24.2 DNA Methylation Studies of Gynecologic Cancers

756

(5)

24.2.1 Genome-Wide Alterations in DNA Methylation

757

(1)

24.2.2 Discovery of DNA Methylation Biomarkers

758

(1)

24.2.3 Identification of Therapeutic Targets by DNA Methylation Profiling

759

(2)

24.3 Organization of the Cell Nucleus, DNA Methylation and Cancer Outcome

761

(7)

24.3.1 The Nuclear Morphology of Gynecologic Cancers

761

(2)

24.3.2 Cancer Methylome in the Context of Higher Order Chromatin Organization

763

(3)

24.3.3 Interplay Between DNA Methylation and Nuclear Morphology

766

(2)

24.4 Conclusion

768

(13)

List of Acronyms and Abbreviations

768

(1)

Glossary

769

(1)

Acknowledgments

770

(1)

References

770

(11)

Chapter 25 Epigenetics in Human Reproduction and Gynecologic Diseases

781

(24)

Kamthorn Pruksananonda

Artisa Wasinarom

Apiwat Mutirangura

25.1 Introduction

781

(1)

25.2 Basic Concepts of Epigenetics

782

(1)

25.3 Gametogenesis

783

(3)

25.3.1 Spermatogenesis

784

(1)

25.3.2 Oogenesis

785

(1)

25.4 Embryogenesis

786

(1)

25.5 Infertility

787

(2)

25.5.1 Male Infertility

788

(1)

25.5.2 Female Infertility

789

(1)

25.6 Role in Assisted Reproductive Technologies

789

(1)

25.7 Transgenerational Inheritance

790

(1)

25.8 Epigenetics in Gynecologic Diseases

790

(7)

25.8.1 Polycystic Ovary Syndrome

791

(1)

25.8.2 Endometriosis

792

(2)

25.8.3 Epithelial Ovarian Cancer

794

(1)

25.8.4 Hydatidiform Mole

794

(1)

25.8.5 Cervical Cancer and Human Papillomavirus

795

(1)

25.8.6 Endometrial Cancer

796

(1)

25.8.7 Uterine Leiomyoma

796

(1)

25.9 Epigenetics and the Prospects for Future Treatment

797

(1)

25.10 Conclusion

798

(7)

References

798

(7)

SECTION VIII DEVELOPMENT, AGING AND TRANSGENERATIONAL EFFECTS

Chapter 26 Epigenetics of Transgenerational Inheritance of Disease

805

(32)

Georgina E.T. Blake

Joanna Rakoczy

Erica D. Watson

26.1 Introduction

806

(1)

26.2 Defining Epigenetic Inheritance

806

(1)

26.3 Multigenerational Inheritance of Human Disease

807

(2)

26.4 Potential Stressors Leading to Epigenetic Inheritance in Humans

809

(3)

26.4.1 Nutrition

809

(1)

26.4.2 Toxicant Exposure: Cigarette Smoking and Air Pollutants

810

(1)

26.4.3 Psychological Stress

811

(1)

26.5 Potential Mechanisms of Epigenetic Inheritance in Humans

812

(1)

26.6 Developing a Mechanistic Understanding of Epigenetic Inheritance in Animal Models

812

(3)

26.6.1 Replicating the Abnormal Epigenome Between Generations

813

(1)

26.6.2 Reconstructing the Abnormal Epigenome Between Generations

813

(2)

26.7 Mechanistic Candidates and Machinery of Transgenerational Epigenetic Inheritance

815

(2)

26.7.1 DNA Methylation

815

(1)

26.7.2 Histone Modifications

816

(1)

26.7.3 Noncoding RNA

816

(1)

26.7.4 Epigenetic "Readers" and "Writers"

817

(1)

26.8 The Classic Mammalian Example: Agouti Viable Yellow

817

(2)

26.9 The Bandwidth of Inheritance

819

(1)

26.10 The Importance of the Repetitive Genome

820

(1)

26.11 Tracking Phenotypes and Epimutations Over Multiple Generations

821

(1)

26.12 Allowing for Phenotypic and Epigenetic Variability

822

(1)

26.13 Considering Genetic Effects

822

(1)

26.14 RNA-Mediated Inheritance of Phenotype

823

(2)

26.15 Interactions Between Epigenetic Mechanisms

825

(1)

26.16 Adaptive Benefits of Epigenetic Inheritance

825

(1)

26.17 Can Our Mechanistic Understanding of Epigenetic Inheritance Be Extrapolated to Human Populations?

826

(1)

26.18 Conclusions

827

(10)

List of Abbreviations

828

(1)

Glossary

828

(2)

Acknowledgments

830

(1)

References

830

(7)

Chapter 27 Epigenomic Mechanisms of Human Developmental Disorders

837

(24)

Erfan Aref-Eshghi

Laila C. Schenkel

Deanna Alexis Carere

David I. Rodenhiser

Bekim Sadikovic

27.1 Introduction

837

(1)

27.2 DNA and Chromatin Modifications

838

(2)

27.3 Epigenetically Regulated Monoallelic Gene Expression: Imprinting Diseases

840

(3)

27.4 Epigenetically Regulated Monoallelic Gene Expression: X-Linked Diseases

843

(1)

27.5 Epigenetic Involvements in Trinucleotide Repeat Diseases

843

(2)

27.6 Diseases of the Epigenomic Machinery Defects

845

(1)

27.7 Interaction of Genetic and Epigenetic Variations in Human Disease

846

(2)

27.8 Epigenomic Involvement in Multifactorial Neurodevelopmental Conditions

848

(2)

27.9 Clinical Utilization of Epigenomic Technologies

850

(11)

References

852

(9)

Chapter 28 Therapeutic Approaches to Imprinting Diseases

861

(16)

Hiromitsu Hattori

Hitoshi Hiura

Norio Kobayashi

Souta Takahashi

Hiroaki Okae

Takahiro Arima

28.1 Introduction

861

(1)

28.2 Assisted Reproductive Technologies and Imprinting Disorders

862

(2)

28.3 Clinical Management

864

(3)

28.4 Future Perspective: Therapies

867

(3)

28.4.1 Diagnostics

867

(1)

28.4.2 Interventions

867

(2)

28.4.3 Therapies

869

(1)

28.5 Conclusion

870

(7)

List of Abbreviations

871

(1)

Acknowledgments

872

(1)

References

872

(5)

Chapter 29 Stem Cell Epigenetics and Human Disease

877

(26)

Leila Larijani

Derrick E. Rancourt

29.1 Introduction

877

(1)

29.2 Epigenetics

878

(2)

29.3 Pluripotent Stem Cells

880

(1)

29.4 Pluripotent Stem Cell Epigenetics

880

(3)

29.4.1 Chromatin Bivalency

881

(2)

29.4.2 Histone Variants and Exchange of Histones

883

(1)

29.5 Changing the Epigenetic Landscape During Cellular Reprogramming

883

(4)

29.5.1 Histone Signatures During Reprogramming

884

(3)

29.5.2 DNA Demethylation During Reprogramming

887

(1)

29.6 Stem Cell Epigenetics and Human Disease

887

(7)

29.6.1 Imprinting Diseases

888

(1)

29.6.2 Rett Syndrome

889

(1)

29.6.3 Alpha Thalassemia/Mental Retardation Syndrome X-Linked

889

(1)

29.6.4 Fragile X Syndrome

890

(1)

29.6.5 Myoclonus-Dystonia

891

(1)

29.6.6 Huntington's Disease

891

(1)

29.6.7 Autism

891

(1)

29.6.8 Parkinson's Disease

892

(1)

29.6.9 Schizophrenia

893

(1)

29.6.10 Heart Disease

893

(1)

29.6.11 Progeria and Cancer

894

(1)

29.7 Future Studies

894

(9)

References

895

(8)

Chapter 30 Noncoding RNA Regulatory Networks, Epigenetics, and Programming Stem Cell Renewal and Differentiation: Implications for Stem Cell Therapy

903

(32)

Alexander M. Tseng

Amanda H. Mahnke

Nihal A. Salem

Rajesh C. Miranda

30.1 Major Types of Stem Cells

904

(5)

30.1.1 Stem Cell Renewal and the Pluripotency Transcription Factor Network: Lessons From Induced Pluripotent Stem Cell Biology

905

(2)

30.1.2 Regulatory Networks and Control of Stem Cell Differentiation

907

(2)

30.2 A Brief Overview of Epigenetics

909

(2)

30.2.1 DNA Methylation, Histone Modifications, and Gene Imprinting

909

(1)

30.2.2 Epigenetics of Noncoding RNAs

910

(1)

30.3 Epigenetic Programming of Stem Cells

911

(11)

30.3.1 Epigenetic Programming, Early Development, and the Core Pluripotency Transcription Factor Network

911

(8)

30.3.2 Epigenetic Programming, Noncoding RNAs, and Early Stem Cell Differentiation Programs

919

(2)

30.3.3 Epigenetic Mutations and Somatic Cell Mosaicism

921

(1)

30.4 Final Comments

922

(13)

References

923

(12)

Chapter 31 Aging and Disease: The Epigenetic Bridge

935

(40)

Andrea Fuso

31.1 Introduction

935

(2)

31.2 Genes and Aging

937

(6)

31.2.1 Main Theories on Aging

938

(1)

31.2.2 Aging, Epigenetics, and Chromatin

939

(4)

31.3 The Dynamic Methylome

943

(4)

31.3.1 Epigenetic Dynamics in the Aging Brain

943

(2)

31.3.2 Complexity of the Age-Associated Epigenetic Changes

945

(2)

31.4 Healthy and Pathological Aging

947

(7)

31.4.1 Environment, Epigenetics, and Aging

948

(2)

31.4.2 Nutrition, Epigenetics, and Aging

950

(1)

31.4.3 Epigenetics and Age-Associated Diseases

951

(2)

31.4.4 Fleeting DNA Hydroxy methylation and Aging-Associated Diseases

953

(1)

31.5 One-Carbon Metabolism

954

(3)

31.5.1 One-Carbon Metabolism in Aging and Neurodegeneration

956

(1)

31.6 Epigenetics and Neurodegeneration: The Alzheimer's Disease Paradigm

957

(3)

31.6.1 Aged Alzheimer's Disease Mice and Epigenetics

958

(1)

31.6.2 Rediscovered Non-CpG Methylation

958

(2)

31.7 Conclusion

960

(15)

References

960

(15)

Chapter 32 Epigenetic Programming of Human Disease and Aging

975

(20)

Alexander M. Vaiserman

Alexander K. Koliada

Oleh V. Lushchak

32.1 Introduction

975

(2)

32.2 Intrauterine Growth Restriction

977

(1)

32.3 Fetal Macrosomia

978

(2)

32.4 Endocrine Programming During Intrauterine Development

980

(6)

32.4.1 Hypothalamic---Pituitary---Adrenal Axis

981

(1)

32.4.2 Growth Hormone/Insulin-Like Growth Factor Axis

982

(1)

32.4.3 Early Life Nutritional Epigenetic Programming of Adult Health Status

982

(4)

32.5 Conclusions and Future Directions

986

(9)

References

987

(8)

SECTION IX FUTURE RESEARCH

Chapter 33 Epigenetic Prospects in Epidemiology and Public Health

995

(24)

Shuai Li

Pierre-Antoine Dugue

Roger L. Milne

John L. Hopper

33.1 Introduction

996

(1)

33.2 Epigenetics in Disease Etiology

996

(2)

33.2.1 Epigenetic Variation as a Disease Cause

996

(1)

33.2.2 Epigenetic Variation as a Mediator of the Effect of Exposure

997

(1)

33.3 Epigenetic Variation as a Biomarker of Exposure

998

(1)

33.4 Epigenetic Variation as a Biomarker of Disease

999

(1)

33.4.1 Epigenetics in Disease Risk Prediction and Intervention

999

(1)

33.5 Epigenetics in Disease Treatment

1000

(1)

33.6 Considerations Regarding the Implementation of Epigenetic Epidemiological Studies

1001

(5)

33.6.1 Research Question

1001

(1)

33.6.2 Study Design

1001

(3)

33.6.3 Sample Size

1004

(1)

33.6.4 Biological Sample

1005

(1)

33.6.5 Measurement Tool

1006

(1)

33.7 Challenges

1006

(4)

33.7.1 Data Analysis

1007

(2)

33.7.2 Interpretation of Results

1009

(1)

33.7.3 Causal Inference

1009

(1)

33.7.4 Communication to the Public

1010

(1)

33.8 Future Directions

1010

(1)

33.9 Summary

1011

(8)

List of Abbreviations

1011

(1)

Acknowledgments

1012

(1)

References

1012

(7)

Index

1019

Dr. Tollefsbol is a Distinguished Professor at the University of Alabama at Birmingham. He holds doctorates in molecular biology and osteopathic medicine, trained with National Academy of Science members and has over 200 peer-reviewed publications. Reports highlighting the translatability to the lay public of the discoveries made in his laboratory have appeared in international media representing >50 million readers. Dr. Tollefsbol has been featured as an Investigator in the Spotlight by the NIH as well as a Scientist in the Spotlight by ScienceNow. He is an Associate Editor for Frontiers in Genetics, a contributor to Lewins GENES classic textbook and Lead Editor for Elseviers Translational Epigenetics Series. Dr. Tollefsbol has been named a Highly Ranked Scholar” worldwide (ScholarGPS). He has been invited for numerous endowed keynote presentations, his research has been highlighted in eScience News and ScienceDaily and he has published 20 scholarly books on topics related to his research.

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