Genomic and Personalized Medicine

Genomic and Personalized Medicine

V1-2

2nd Edition - October 30, 2012
  • Editors-in-Chief: Geoffrey Ginsburg, Huntington Willard
  • eBook ISBN: 9780123822284

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Description

Genomic and Personalized Medicine, Second Edition — winner of a 2013 Highly Commended BMA Medical Book Award for Medicine — is a major discussion of the structure, history, and applications of the field, as it emerges from the campus and lab into clinical action. As with the first edition, leading experts review the development of the new science, the current opportunities for genome-based analysis in healthcare, and the potential of genomic medicine in future healthcare. The inclusion of the latest information on diagnostic testing, population screening, disease susceptability, and pharmacogenomics makes this work an ideal companion for the many stakeholders of genomic and personalized medicine. With advancing knowledge of the genome across and outside protein-coding regions of DNA, new comprehension of genomic variation and frequencies across populations, the elucidation of advanced strategic approaches to genomic study, and above all in the elaboration of next-generation sequencing, genomic medicine has begun to achieve the much-vaunted transformative health outcomes of the Human Genome Project, almost a decade after its official completion in April 2003.

Key Features

  • Highly Commended 2013 BMA Medical Book Award for Medicine
  • More than 100 chapters, from leading researchers, review the many impacts of genomic discoveries in clinical action, including 63 chapters new to this edition
  • Discusses state-of-the-art genome technologies, including population screening, novel diagnostics, and gene-based therapeutics
  • Wide and inclusive discussion encompasses the formidable ethical, legal, regulatory and social challenges related to the evolving practice of genomic medicine
  • Clearly and beautifully illustrated with 280 color figures, and many thousands of references for further reading and deeper analysis

Readership

Specialists across medical disciplines, research professionals in human genetics/genomics, oncology, neuroscience, gene therapy, molecular medicine, and related areas. It will be indispensable to medical students and graduate students in genetics and biomedical sciences.

Table of Contents

  • Foreword

    Preface

    Acknowledgments

    Abbreviations

    Contributors

    Volume 1

    Chapter 1. The Human Genome: A Window on Human Genetics, Biology, and Medicine

    Introduction

    The Human Genome

    Variation in the Human Genome

    Expression of the Human genome

    Genes, Genomes, and Disease

    From Genomes to Personalized Medicine

    Conclusion

    References

    Chapter 2. Mapping the Functional Genome: The ENCODE and Roadmap Epigenomics Projects

    Introduction

    General Organization and Directives for ENCODE and Roadmap

    Scientific Parameters and Elements of the Projects

    Challenges and the Future

    References

    Recommended Resources

    Chapter 3. Population Perspectives on Genome Variation and Complex Disease

    Introduction

    Why Study Complex Disease in Populations?

    What can be Studied? Phenotypes in Population Genomic Studies of Complex Disease

    Human Population History and the Reservoir of Human Genome Sequence Variation

    Human Genomes Contain Footprints of Human Evolution and the Human Past

    Conclusions

    References

    Chapter 4. Gene–Environment Interactions: Eco-Genetics and Toxicogenomics

    Introduction

    Eco-Genetics

    Methods to Study G × E Interactions

    Nutrigenomics

    Pathogens and Host Susceptibility or Resistance Gene Variants

    Inhaled Chemical Air Pollutants and Allergens and Sensitizing Agents

    Examples of Risk Factors

    Epigenomics and the Environment

    Effects on Protein Folding

    Toxicogenomics and Predictive Toxicology

    Will Personalized Genomic Risk Profiles Motivate PEOPLE to Adopt More Healthful Behaviors?

    Future Prospects: Balancing the Gxe Equation

    References

    Recommended Resources

    Chapter 5. Systems Biology and Systems Medicine

    Introduction

    Systems Science in Biology and Medicine

    Multi-Parameter Blood-Borne Biomarkers

    Emerging in Vivo and in Vitro Technologies

    Computational and Mathematical Challenges in Systems Medicine

    Conclusions and Perspectives

    References

    Chapter 6. Personal Genomics

    Introduction

    Domains of Personal Genomics

    Key Ethical, Legal, and Social Questions

    Personal Genomics and Research Participation

    Summary

    References

    Recommended Resources

    Chapter 7. Whole-Genome Sequencing: New Technologies, Approaches, and Applications

    Introduction

    Fundamentals of Next-Generation Sequencing Instruments

    Considerations of Next-Generation Sequence Read Data

    Fundamentals of Whole-Genome Sequencing

    Bioinformatics-Based Discovery with Whole-Genome Sequencing Data

    Validation of Identified Variants by Orthogonal Data

    Future Prospects and Challenges for Whole-Genome Sequencing

    Clinical Applications of Whole-Genome Sequencing to Cancer

    References

    Recommended Resources

    Chapter 8. Human Genome Variation Discovery via Exome and Whole-Genome Sequencing

    Introduction

    Population-Based Variation Discovery

    Sequencing Approaches to Variation Discovery

    Informatic Approaches to Variation Discovery

    Exome and Whole-Genome Sequencing in Rare Early-Onset Disease

    References

    Chapter 9. Clinical Genome Sequencing

    Introduction

    Challenges of Genome Sequencing in the Clinical Laboratory

    Challenges of Using Genome Sequencing in Medical Practice

    Conclusions

    Acknowledgments

    References

    Chapter 10. Structural Genomic Variation in the Human Genome

    Introduction

    Basic Principles of Copy Number Variation

    Detecting CNVs in a Genome-Wide Manner

    Association of CNVs to Disease and Disease Susceptibility

    Implications of CNVs

    References

    Recommended Resources

    Chapter 11. Clinical Applications of Whole-Genome Chromosomal Microarray Analysis

    Introduction

    Whole-Genome Copy Number Variant Arrays Designed for Clinical Diagnostic Use

    Interpretation of CMA in a Clinical Setting

    Incomplete Penetrance and Variable Expressivity

    CMA in Postnatal Populations

    Potential for CMA in other Clinical Settings

    Whole-Genome CMA as a Model for the Clinical Introduction of Whole-Genome Sequencing

    Summary and Conclusions

    References

    Recommended Resources

    Chapter 12. Transcriptomics in the Age of Ultra High-Throughput Sequencing

    Introduction

    A Paradigm Shift in Gene Expression Analysis

    Quantitative Analysis of Novel and Alternative Expression

    Nucleotide-Level Sequence Differences in Transcriptomes

    Utility of SNVs for Analyzing Tumor Transcriptomes

    Correspondence of SNVs with Gene Expression in Healthy Individuals

    MicroRNAs as Biomarkers

    Perspectives

    References

    Chapter 13. Quantitative Proteomics in Genomic Medicine

    Introduction

    Clinical Proteomics

    Enabling Technologies of Proteomics

    Exemplar Clinical Proteomics Study

    Summary

    References

    Recommended Resources

    Chapter 14. The Human Microbiome and Personalized Medicine

    Introduction

    The Relationship Between Human Microbes and Disease

    Advanced Technologies for the Study of the Human Microbiome

    International Metagenome Projects

    Personalized Medicine Targeting our “Other” Genome

    References

    Recommended Resources

    Chapter 15. Glycomics, Glycobiology, and Glyco-Medicine

    Introduction

    Glycomics

    Biosynthetic Pathways and Glycan Functions

    Congenital Disorders of Glycosylation

    Examples of Multisystemic Disorders

    Disorders with More Restricted Phenotypes

    Other Disorders Affecting N-Glycans

    Excessive N-Glycosylation?

    Disorders in Golgi Homeostasis

    Defects of O-Linked Glycosylation

    Defects in O-Xylose Glycosaminoglycans

    Defects in O-Galnac Glycans

    Defects in O-Fucose Glycans

    Defects in Glycolipid Synthesis

    Conclusions and Perspectives

    Acknowledgments

    References

    Chapter 16. Genome-Wide RNA Interference Screening

    Introduction

    Brief History of RNAi

    General Mechanisms of RNAi

    RNAi Screening

    Validation and Analysis

    Future of RNAi Technology and Therapeutics

    References

    Chapter 17. Application of Human Genome Information to Clinical Practice

    Introduction

    Genome-Wide Variation and Medicine

    Whole-Genome Sequencing for the Clinic

    Family History

    Assessment of Chronic Disease Risk

    Diagnosis and Disease Classification Using Molecular Profiles

    Single and Multimarker Predictors of Prognosis

    Drug Response

    A Roadmap for Translation

    Challenges to clinical Application

    Privacy

    New Models needed for translational Genomics

    Summary

    References

    Chapter 18. Genomic, Personalized Medicine and Public Health

    Introduction

    Public Health Assessment

    Preventive and Preemptive Medicine

    Assessing Validity and Utility

    Conclusion

    References

    Recommended Resources

    Chapter 19. Biospecimen Banking in the Post-Genome Era

    Introduction

    Garbage In, Garbage Out

    Preanalytical Variations

    Importance of Standardization

    Researchers’ Biobank Wish List

    Biobanks Must Evolve

    Need for Guidelines

    Need for Biospecimen Research

    Need for Investment

    Conclusions

    Acknowledgments

    References

    Recommended Resources

    Chapter 20. Designing Genomics-Based Clinical Studies

    Introduction

    Stages of Development and Validation of Prognostic and Predictive Classifiers

    Validation of Prognostic Biomarkers

    Prospective Validation of Predictive Biomarker Classifiers

    Predictive Analysis of Clinical Trials

    Conclusion

    References

    Recommended Resource

    Chapter 21. Genomic Biomarkers in Human Population Studies

    Genomic Biomarkers

    Genetic Biomarkers for Intermediate Phenotypes

    The Use of Genomic Biomarkers in Risk Prediction

    Pharmacogenetics

    Future Directions

    References

    Chapter 22. Validation of Candidate Protein Biomarkers

    Introduction

    From Discovery to Validation

    Validation of Protein Biomarkers

    Preferred Methods of Validating Protein Biomarkers

    Emerging Technologies for Validating Protein Biomarkers

    Conclusion

    References

    Chapter 23. Translational Bioinformatics for Genomic Medicine

    Introduction

    Diagnosis

    Therapeutics

    Histopathology

    Nosology

    Analytic Methods

    Where Data for Studies may be Found

    Bioinformatics Vocabularies and Ontologies

    Freely Available Bioinformatics Tools

    Conclusion: High-Bandwidth Approaches for Genomic Medicine

    Acknowledgments

    References

    Recommended Resources

    Chapter 24. Electronic Health Records in Genomic Medicine

    Introduction

    EHRs and Genomic Information

    Federal Influence on EHR Development

    Opportunities for Integration of Genomic Information with EHRs

    EHR End-User Case Study: the Geisinger Health System

    Conclusion

    References

    Chapter 25. Clinical Implementation of Genomic Medicine in Primary Care

    Introduction

    Role in Primary Care

    Barriers

    Summary

    A Case Study: Genomic Markers for Type 2 Diabetes Mellitus Risk

    References

    Chapter 26. Family History and Health Risk Assessment

    The Rationale for Familial Risk Assessment

    The Rationale for Family History Tools

    Family History Tools: Development, Structure, and Applications

    Test Performance of Family History Tools

    Family History, Risk Perception and Motivation of Healthy Behaviors

    Clinical Decision Support

    References

    Recommended Resources

    Chapter 27. Clinical Decision Support

    Introduction

    Brief History of CDS and Prototypical Systems

    Application of CDS to Support Genomic and Personalized Medicine

    Challenges and Potential Solutions

    Conclusion

    Acknowledgments

    Disclosures

    References

    Recommended Resources

    Ongoing Research

    Chapter 28. Knowledge Management to Support Personalized Healthcare

    Introduction to Knowledge Management

    Policy Implications

    Infrastructure to Support Knowledge Management

    Case Study

    The Business Case for Knowledge Management

    Summary

    References

    Chapter 29. Delivery of Personalized Medicine in an Integrated Healthcare System

    Introduction

    The Clinical Problem – Identification of Patients with Lynch Syndrome

    Building on Success

    Conclusion

    References

    Recommended Resources

    Chapter 30. Pharmacogenomics in Drug Discovery and Development

    Introduction

    Identifying New Molecular Targets for Drug Discovery

    Pharmacogenomics of Drug Absorption, Distribution, Metabolism, and Elimination

    Pharmacogenomics in Drug Development

    Conclusions

    References

    Recommended Resources

    Chapter 31. Pharmacogenetics and Pharmacogenomics

    Introduction

    Molecular Diagnostics for Optimizing Drug Therapy

    Drug Metabolism

    Genetic Polymorphisms of Drug Targets

    Global Health Applications

    Application in Drug Development

    Challenges Going Forward

    References

    Recommended Resources

    Chapter 32. Point-of-Care Devices

    Introduction

    Point-of-Care Devices: Design Considerations, Progress of Development

    Novel Sensor Implementation for Point of Care Devices

    Current Challenges and Outlook for Point of Care Devices

    References

    Chapter 33. Patient-Specific Pluripotent Stem Cells

    Introduction

    Reprogramming: An Evolving Technology

    Generating Disease-Relevant Cell Types from Human Stem Cells

    Working toward the Ultimate Goal: Transplantation and Tissue Engineering

    Additional Roles for Patient-specific iPS Cells

    Summary

    References

    Chapter 34. Overview of Policy, Ethical and Social Considerations in Genomic and Personalized Medicine

    Introduction

    Ethical Issues in Large-Scale Genetics and Genomics Research and Individual Whole-Genome Analysis

    Integrating Genomic Medicine Applications in Healthcare

    Conclusion

    References

    Chapter 35. Informed Consent

    Introduction

    When is Informed Consent Required?

    Informed Consent Disclosures and Comprehension

    Special Considerations

    Conclusions

    References

    Recommended Resources

    Chapter 36. Educational Issues and Strategies for Genomic Medicine

    Introduction

    Gaps in Current Understanding

    Educational Opportunities to Close the GAPS

    The Future

    Concluding Thoughts

    References

    Recommended Resources

    Chapter 37. Regulatory Issues for Genomic Technologies

    Introduction

    Regulation of Genomic Tests: an Overview

    Pharmacogenomics in Drug Development and Clinical Medicine: the Role of Regulation

    Federal Regulation of Genetic Therapeutics

    FDA Efforts to Advance Genomic Product Development

    Conclusions

    References

    Recommended Resources

    Chapter 38. Challenges and Regulation of Direct to Consumer Testing

    Introduction

    The Meaning of “DTC”

    Risks and Benefits

    Consumer Impact

    Federal Oversight of DTC Testing

    Conclusion

    References

    Recommended Resources

    Chapter 39. Economic Issues and Genomic Medicine

    Introduction

    Economic Evaluation and Cost-Effectiveness Analysis

    Evaluating Genomic Technologies

    Economic Incentives and the Future of Genomic Medicine

    Summary

    References

    Chapter 40. Strategic Issues in the Adoption of Genome-Based Diagnostics

    Introduction

    Clinical Validation

    Modulators of Test Adoption

    Regulatory Requirements

    Physician Practice Factors Associated with Test Adoption

    Companion Diagnostics

    Maturity/Plateau Phase

    Conclusions

    References

    Chapter 41. Reimbursement

    Introduction

    Coding, Coverage, and Payment

    Conclusions and Outlook

    References

    Recommended Resources

    Chapter 42. Genomics and Patents: A Practical Guide for Genome Scientists and Clinical Researchers

    Introduction

    Some Famous Cases

    Some Questions About Patenting and Licensing Genomic Inventions

    Conclusions

    References

    Recommended Resources

    Chapter 43. Public–Private Partnerships in Biomarker Research

    Introduction

    The Challenge of Biomarker Research and Development

    The Growth of Public–Private Partnerships in Biomarker Research

    Public–Private Partnerships in Biomarker Research

    Common Challenges and Approaches

    Critical Success Factors

    The Future of Biomarker PubLic–Private Partnerships

    References

    Recommended Resources

    Volume 2

    Chapter 44. Hypertension

    Introduction

    Finding Blood Pressure Genes

    New Insights into Blood Pressure Biology

    Developing New Therapies for Cardiovascular Disease

    Utility of a Genetic Risk Score

    Conclusion

    Acknowledgments

    References

    Chapter 45. Lipoprotein Disorders

    Introduction

    Overview of Lipoprotein Metabolism

    Inherited Basis of Plasma Lipid Traits

    Mendelian Disorders of Lipoprotein Metabolism

    Association of Common Variants with Plasma Lipid Traits and Relationship to Cardiovascular Disease

    Future Directions

    References

    Chapter 46. Coronary Artery Disease and Myocardial Infarction

    Introduction

    Scanning for Susceptibility SNPs

    Mendelian Randomization

    Lipid Traits

    Coronary Artery Disease and Myocardial Infarction

    Pharmacogenomics

    Non-DNA Approaches to CAD and MI

    Future Directions

    References

    Chapter 47. Atherosclerosis, Vulnerable Plaques, and Acute Coronary Syndromes

    Plaque Rupture and Erosion

    Plaque Vulnerability

    Challenges for Prevention

    Personalized Risk Prediction

    Challenges for Treatment of Advanced Atherosclerosis

    References

    Chapter 48. Heart Failure

    Definitions

    Predisposition – Genetic and Non-Genetic

    Screening

    Pathophysiology

    Diagnosis

    Prognosis

    Monitoring

    Novel Therapeutics and Future Directions

    Disease Modeling for Personalized Healthcare

    Conclusions and Recommendations

    Acknowledgments

    References

    Chapter 49. Cardiac Transplant Rejection

    Introduction

    Types of Cardiac Allograft Rejection

    Immunosuppression Strategies to Prevent Rejection

    Strategies for Monitoring Transplant Recipients

    Development of a Gene Expression Signature for Acute Cellular Rejection in Cardiac Transplant Recipients

    Pathways Monitored by the AlloMap® Test

    Regulatory Approvals of the AlloMap® Test

    Clinical Use of the AlloMap® Test

    Future Directions of Gene Expression Profile Testing

    References

    Chapter 50. Hypertrophic Cardiomyopathies

    Definitions, Clinical Presentation and Diagnosis

    Molecular Genetics of Hypertrophic Cardiomyopathy

    Screening and Treatment for HCM

    Conclusions

    References

    Chapter 51. Arrhythmias

    Introduction

    Inherited Arrhythmia Syndromes and Arrhythmia Mechanisms

    Gene- and Mutation-Specific Features in Inherited Arrhythmia Syndromes

    Genetic and Genomic Modifiers in Inherited Arrhythmia Syndromes

    Bradyarrhythmias and Mechanisms of Heart Rate Control

    Genetic and Genomic Modifiers of Heart Rate

    Atrial Fibrillation/Flutter and Arrhythmia Mechanisms

    Genetic and Genomic Modifiers in Atrial Fibrillation

    Ventricular Tachyarrhythmias and Mechanisms of Sudden Cardiac Death

    Genetic and Genomic Modifiers of Sudden Cardiac Death

    Genetic and Genomic Modifiers of Arrhythmia Therapies

    Clinical Applications of Genetic Testing

    Conclusion

    References

    Chapter 52. Hemostasis and Thrombosis

    Hemostasis and Blood Coagulation

    Evolutionary Genomics and Coagulation

    Heritability of Coagulation

    Genetics of Platelet Function

    Genetic–Environmental Interface

    Race, Culture, and Ethnicity

    Patient and Population Screening

    Treatment Considerations in Thrombosis and Pharmacogenetics

    Pharmacogenetics

    Future Directions in Genetics and Genomics

    References

    Chapter 53. Peripheral Arterial Disease

    Introduction

    Epidemiology and Risk Factors for Peripheral Arterial Disease

    Clinical Manifestations of Peripheral Arterial Disease

    Therapeutic Strategies for Peripheral Arterial Disease

    Intermittent Claudication and Critical limb Ischemia are Distinct Clinical Outcomes of Peripheral Arterial Disease

    Genetic Susceptibility to Peripheral Arterial Disease

    Biomarkers of Peripheral Arterial Disease

    Future Potential use of Genomic Methodologies in Peripheral Arterial Disease

    References

    Chapter 54. Congenital Heart Disease

    Introduction

    What is Congenital Heart Disease?

    Origins of Congenital Heart Disease

    Congenital Heart Disease and Single Gene Disorders

    Origins of Pleiotropic Heart Defects in Single Gene Disorders

    What are Complex Traits?

    Issues to Consider in Future Studies

    Summary

    References

    Recommended Resources

    Chapter 55. Perioperative Genomics

    Scientific Rationale for Perioperative Genomic Medicine

    Perioperative Cardiac Adverse Events

    Perioperative Atrial Fibrillation

    Postoperative Event-Free Survival

    Postoperative Stroke and Neurocognitive Dysfunction

    Perioperative Acute Kidney Injury

    Dynamic Genomic Markers of Perioperative Outcomes

    Conclusions

    Acknowledgments

    References

    Chapter 56. Stroke

    Introduction

    Dissecting the Stroke Phenotype

    Heritability of Stroke

    Monogenic Forms of Stroke

    Genomics of Common Complex Stroke

    Pharmacogenetics

    Overcoming Heterogeneity in the Stroke Phenotype

    Future Directions

    Clinical Implications of Genomic Discoveries in Stroke

    Conclusion

    Acknowledgments

    References

    Chapter 57. Lymphomas

    Introduction

    Clinical Presentation and Staging

    The Role of Key Genes in Lymphoma

    MicroRNA

    Gene Expression Signatures

    Genomics by Lymphoma Type

    Summary

    References

    Chapter 58. Leukemias

    Introduction

    Leukemia Cytogenetics and Molecular Genetics

    A Decade of Transcriptomics in Leukemia

    Genomics has Opened New Avenues in Leukemia Research

    Leukemia Epigenomics

    Proteomics and Functional Genomics – The Future has Begun

    Future Challenges of Genomics in Leukemia

    Acknowledgments

    References

    Recommended Resources

    Chapter 59. Lung Cancer

    Introduction

    Early Diagnosis/Screening of Lung Cancer

    Classification and Prognosis

    Pathogenesis and Treatment of Lung Cancer

    Conclusion

    References

    Chapter 60. Breast Cancer

    Introduction

    Risk Factors

    Prognostic Factors

    Predicting Therapeutic Response

    Discovery of New Biomarkers

    Individualizing Treatment

    References

    Chapter 61. Ovarian Cancer

    Origins of Epithelial Ovarian Cancer

    Inherited Syndromes of Ovarian Cancers

    Genome-Wide Association Studies

    Transcriptional Profiling of Ovarian Cancer Histologic Subtypes

    Metastasis of Ovarian Cancers

    Integrated Genomic Analyses of Ovarian Carcinoma

    Angiogenesis

    Epigenetics

    Pharmacogenomics and Ovarian Cancer

    Summary

    References

    Chapter 62. Colorectal Cancer

    Introduction

    Genetics of Colorectal Cancer

    Epigenetics of Colorectal Cancer

    Genetics of Colorectal Cancer-Associated Syndromes

    Missing Heritability in Colorectal Cancer

    “Epimutations” and Hereditary Colorectal Cancer

    Gene Silencing from Transcriptional Read-Through

    Novel Colorectal Cancer Predisposing Genes

    Functional Grouping of Variants in Pathways

    Moderate Risks and Modifier Genes

    Perspectives

    Acknowledgments

    References

    Chapter 63. Prostate Cancer

    Introduction

    Germline Genetics of Prostate Cancer

    Somatic Genetics of Prostate Cancer

    Epigenetics of Prostate Cancer

    Conclusions

    References

    Chapter 64. Head and Neck Cancer

    Head and Neck Squamous Cell Carcinoma

    Conclusion

    References

    Chapter 65. Brain Tumors and Gliomas

    Introduction

    Predisposition

    Screening

    Diagnosis and Prognosis

    Pharmacogenomics

    Monitoring

    Novel and Emerging Therapeutics

    Conclusions

    References

    Chapter 66. Melanoma

    Introduction

    Melanoma Progression

    Genetics of Melanoma

    Genomic Strategies to Characterize Melanoma

    Clinical Applications of Genomics in Melanoma

    Conclusion

    References

    Recommended Resources

    Chapter 67. Metastatic Cancer

    Introduction

    The Genetics of Metastasis

    The Genomics of Metastasis

    New Treatment Possibilities for Metastatic Cancer

    Clinical Diagnostics

    Conclusions

    References

    Recommended Resources

    Chapter 68. Bioinformatics in Personalized Cancer Care

    Introduction

    Biomedical Informatics Capabilities Driven by the Study of Cancer

    Translatable Informatics

    Toward an IT-Enabled Ecosystem

    References

    Recommended Resources

    Chapter 69. Diagnostic-Therapeutic Combinations

    Introduction

    Targeted Therapies for Cancer

    The Ideal Target

    The First Diagnostic-Therapeutic Combination

    Diagnostic-Therapeutic Combinations for Leukemia and Lymphoma

    Selected Targeted Anticancer Therapies Using Small Molecules

    Pharmacogenomics

    Pharmacogenetics

    Whole Genome Analysis by Next-Generation DNA Sequencing

    Developing Diagnostic-Therapeutic Combinations

    Conclusion

    References

    Chapter 70. Autoimmune Disorders

    Introduction

    HLA and Autoimmunity

    Gene Discovery in Autoimmunity: The Example of Multiple Sclerosis

    Systematic Assessment of Commonalities and Differences Among Autoimmune Diseases

    The Next Steps in Complex Genetics Research

    Systems Biology

    Conclusions

    References

    Chapter 71. Rheumatoid Arthritis

    Introduction

    Clinical Features

    Predisposition

    Screening

    Diagnosis, Prognosis, and Monitoring

    Pharmacogenomics

    Conclusions

    References

    Chapter 72. Multiple Sclerosis

    Introduction

    Genomics

    Transcriptomics

    Immunomics

    Proteomics

    Platforms for the Identification of New Therapeutic Targets

    Conclusion

    References

    Chapter 73. Inflammatory Bowel Disease

    Introduction

    Epidemiology

    Disease Phenotypes

    Pathogenesis and Risk Factors

    What Was Known Before Genome-Wide Association Studies

    Genome-Wide Association Study Findings

    Implications of Disease-Associated Loci to Pathogenesis

    Risk Prediction

    Pharmacogenomics

    Conclusion

    References

    Ongoing Research

    Recommended Resources

    Chapter 74. Asthma

    Introduction

    Candidate Gene Studies

    Positionally Cloned Genes

    Whole-Genome Association Studies

    Vitamin D and Asthma

    Lessons Learned

    References

    Chapter 75. Chronic Obstructive Pulmonary Disease

    Summary

    Introduction

    Predisposition

    Pathophysiology

    Cellular and Molecular Mechanisms

    Diagnosis and Screening

    Prognosis

    Management

    New Treatments

    Conclusions

    References

    Chapter 76. Interstitial Lung Disease

    Introduction

    Genetic Determinants of Diffuse Parenchymal Lung Disease in Mouse Strains

    Genetic Determinants of Sarcoidosis

    Genomic Medicine and Sarcoidosis

    Proteomics in Sarcoidosis

    Surfactant Proteins and Diffuse Parenchymal Lung Disease

    Genetic Determinants of Pulmonary Fibrosis Identified in Rare Inherited Disorders

    Genetic Determinants of Familial Interstitial Pneumonia

    Conclusion

    References

    Recommended Resources

    Chapter 77. Peptic Ulcer Disease

    Introduction

    The Helicobacter Genome and Virulence Markers

    Host Polymorphisms

    Pharmacogenomics

    Proteomics and Genomics of Ulcer Detection

    Genomics and Treatment of Peptic Ulcers

    Conclusions

    Acknowledgments

    References

    Ongoing Research

    Chapter 78. Cirrhosis

    Introduction

    Liver Structure

    Fibrosis and Cirrhosis

    Diagnosis of Cirrhosis

    Treatment of Cirrhosis

    Genetics of Cirrhosis

    The Liver Transcriptome

    The Liver Proteome

    Development of Liver Fibrosis

    Transcriptome Analysis of Liver Disease

    Proteomic Studies of Liver Disease

    Genetic Markers and Pharmacogenomics of Liver Fibrosis

    Future Impact of Genomics

    Conclusions

    References

    Chapter 79. Systemic Sclerosis

    Definition

    Subsets of SSC

    Epidemiology

    Etiology and Pathogenesis

    Genetic Markers

    Clinical Presentation

    Development of the Classification Criteria for SSC

    Prognostic Markers and Systemic Sclerosis Activity Score

    Treatment

    Prognosis

    References

    Chapter 80. Systemic Lupus Erythematosus

    Classification and Clinical Features

    Epidemiology and Etiology

    Mendelian SLE – The Role of Rare Variants

    SLE and the MHC

    Genome Wide Association Studies

    SLE and Copy Number Variation

    Epigenetics

    The Current Genetic Model and its Uncertainties

    Genomics and the Prediction of Disease

    Genomics and the Prediction of Clinical Manifestations

    Genomics and Individualized Prescribing

    References

    Recommended Resources

    Chapter 81. Osteoarthritis

    Personalized Medicine – Choice Versus Cost

    Osteoarthritis – The Magnitude of the Problem

    Paradigms for Studying Early Osteoarthritis Events

    Identifying the Molecular Stage of Osteoarthritis

    Joint Injury as a Paradigm for Early OA Identification and Treatment

    Advantages of Early Arthritis Identification Illustrated by Rheumatoid Arthritis

    Outlook for the Future

    References

    Chapter 82. Diabetes

    Introduction

    Epidemiology and Genetics

    The Search for Genetic Determinants of Type 2 Diabetes

    Insights Gained from Genetic Studies in Type 2 Diabetes

    Conclusions and Future Directions

    Acknowledgments

    References

    Chapter 83. The Metabolic Syndrome

    Introduction

    Heritability of Metabolic Syndrome

    Lessons from Monogenic Models of Metabolic Syndrome

    Genetics of Common Metabolic Syndrome

    The Thrifty Gene Hypothesis

    Finding the Missing Heritability

    Clinical Implications to Genetic Findings in Metabolic Syndrome

    Conclusion

    Acknowledgments

    References

    Chapter 84. Neuroscience and the Genomic Revolution: An Overview

    Introduction

    Challenges for Genetics in Neuroscience

    The Genetic Architecture of Neuropsychiatric Disorders

    Environmental and Epigenetic Interactions in Neurogenetics

    The Outlook for Personalized and Genomic Medicine in Neuroscience

    Conclusion

    References

    Recommended Resources

    Chapter 85. Alzheimer’s Disease

    Introduction

    Early-Onset Familial AD with Mendelian Transmission

    Late-Onset AD without Mendelian Transmission

    AD Genetics Beyond GWAS

    Conclusion

    References

    Recommended Resources

    Chapter 86. Parkinson’s Disease

    Introduction

    The Need for Reliable Parkinson’s Disease Biomarkers

    Technology for Protein Identification and Validation

    Unbiased Profiling Using Cerebrospinal Fluid

    Unbiased Profiling Using Brain Tissue

    Targeted Validation of Candidate Biomarkers

    From Discovery to Validation

    Concluding Remarks

    Acknowledgments

    References

    Chapter 87. Epilepsy

    Introduction

    Why Genomic and Personalized Medicine in Epilepsy?

    Genomics in Epilepsy: What Do We Know?

    The Future: Challenges and Potential

    References

    Chapter 88. Schizophrenia and Bipolar Disorder

    Introduction

    GWAS for Schizophrenia and Bipolar Disorder

    Studies of Copy Number Variation

    Role of CNVs in Schizophrenia and Bipolar Disorder

    Conclusions and Future Directions

    References

    Chapter 89. Depression

    Introduction

    Diagnosis, Prevalence, and Course of Depression

    Molecular Neurobiology of Depression

    Genetic Basis of Major Depression

    Conclusions and Future Aspects of Depression Genomics

    References

    Chapter 90. Autism Spectrum Disorders

    Introduction

    Defining Autism in the Clinic and in the Laboratory

    “Syndromic” Associations with ASD

    Chromosomal Disorders and Copy Number Variants

    “Nonsyndromic” Genes for ASD

    Recessive Mutations in ASD

    What are the Roles of Common Variants in ASD?

    Early Results of Whole-Exome and Whole-Genome Sequencing in ASD

    Mechanistic Insights into Autism from Genetic Studies

    Acknowledgments

    References

    Ongoing Research

    Chapter 91. Eye Diseases

    Introduction

    Genome-Wide Association Studies

    Functional Genomics

    Pharmacogenomics

    Whole-Exome and Whole-Genome Sequencing

    Gene-Based Therapies for Ocular Disease

    Epigenetics

    Ocular Genetic and Genomic Resources

    Outlook for the Future

    References

    Chapter 92. Glaucoma

    Introduction

    Primary Open-Angle Glaucoma

    Exfoliation Glaucoma

    Primary Congenital Glaucoma

    Developmental Glaucoma

    Glaucoma Genetics and Personalized Medicine

    References

    Recommended Resources

    Chapter 93. Diagnosis and Classification of Pathogens

    Introduction

    Hypothesis and In Vitro Studies

    In Vitro Studies

    Initial Human Studies: Proof of Concept

    New Areas for Improving Diagnosis

    References

    Chapter 94. Host–Pathogen Interactions

    Introduction

    Host Response to Bacterial Pathogens

    Bacterial Response to the Host

    Future Perspective

    References

    Chapter 95. Microbial Vaccine Development

    Introduction

    The Ideal Vaccine and Measurement of Response

    The Biology of Immune Response to Vaccines

    Small Animal Models

    Studies in Non-Human Primates and Humans

    Practical Considerations

    Conclusions

    Acknowledgments

    References

    Chapter 96. Bacterial Infections

    Introduction

    In Vitro Studies: Host Cell Responses

    In Vivo Studies: Genomic Technologies

    Future Directions

    Conclusion

    Acknowledgments

    References

    Chapter 97. Emerging Viral Infections

    Introduction

    Viral Genomics

    Host Genomics

    Future Challenges

    Acknowledgments

    References

    Chapter 98. Sepsis

    Introduction

    Definitions, Incidence, and Temporal Dynamics

    Genetic Variations Associated with Sepsis

    Pathogen Recognition/Signaling

    Cytokine Polymorphisms

    Coagulation

    Metabolism

    Neurohormonal System

    Future Investigations

    Integrative Genomics, Molecular Signatures, and Sepsis

    Therapeutics

    Conclusions

    References

    Chapter 99. Viral Hepatitis

    Introduction

    Virology of Hepatitis Viruses

    Acquisition and Predisposition to Viral Hepatitis

    Screening and Diagnosis of Viral Hepatitis

    Viral Hepatitis Prognosis and Natural History

    Therapeutics and Pharmacogenomics

    Future Impact of GenomicS

    ConclusionS

    References

    Chapter 100. Malaria

    Introduction

    Malaria and its Causal Agent

    Pathogenesis in the Human Host and Immunity

    Genomics for the Development of New Antimalarial Strategies

    Personalized Medicine and Malaria: How, Where, and When

    Acknowledgment

    References

    Chapter 101. HIV Pharmacogenetics and Pharmacogenomics

    Introduction

    Pharmacogenetics of Combined Antiretroviral Therapy Toxicity

    Established Pharmacogenetic Predictors in HIV Treatment

    The Future of HIV Pharmacogenetics and Pharmacogenomics

    Conclusions

    References

    Recommended Resources

    Glossary

    Index

Product details

  • No. of pages: 1350
  • Language: English
  • Copyright: © Academic Press 2012
  • Published: October 30, 2012
  • Imprint: Academic Press
  • eBook ISBN: 9780123822284

About the Editors in Chief

Geoffrey Ginsburg

Dr. Ginsburg is the founding Director of the Center for Applied Genomics & Precision Medicine in the Duke Institute for Genome Sciences & Policy. He is also Professor of Medicine and of Pathology at Duke University Medical Center, Professor of Biomedical Engineering at Duke Pratt School of Engineering, and Co-Director of the Duke Translational Medicine Institute.

Affiliations and Expertise

Duke Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA

Huntington Willard

Huntington Willard is on the faculty of the Department of Human Genetics at the University of Chicago. Prior to this appointment, Willard was the President and Director of the Marine Biological Laboratory and Professor of Human Genetics at the University of Chicago. He was previously on the faculty at Duke University, where he was founding director of the university-wide Duke Institute for Genome Sciences & Policy from 2003 to 2014, the Nanaline H. Duke Professor of Genome Sciences, and the Arts & Sciences Professor of Biology & Genome Sciences.

Affiliations and Expertise

Director and Principal, Geisinger National Precision Health, North Bethesda, Maryland, USA