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Genomic and Personalized Medicine
V1-2
- 2nd Edition - October 30, 2012
- Editors: Geoffrey S. Ginsburg, Huntington F Willard
- Language: English
- eBook ISBN:9 7 8 - 0 - 1 2 - 3 8 2 2 2 8 - 4
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 app… Read more
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Request a sales quoteGenomic 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.
- 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
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.
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
- No. of pages: 1350
- Language: English
- Edition: 2
- Published: October 30, 2012
- Imprint: Academic Press
- eBook ISBN: 9780123822284
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Geoffrey S. 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
Chief Medical and Scientific Officer, All of Us Research Program, National Institutes of Health, Bethesda, Maryland, USAHW
Huntington F 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
Chief Scientific Officer, Genome Medical, Inc., South San Francisco, CA, USARead Genomic and Personalized Medicine on ScienceDirect