Ginsburg / Willard Essentials of Genomic and Personalized Medicine

1. Auflage 2009
ISBN: 978-0-08-095811-8
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 851 Seiten

Derived from the comprehensive two-volume set, Genomic and Personalized Medicine also edited by Drs. Willard and Ginsburg, this work serves the needs of the evolving population of scientists, researchers, practitioners and students that are embracing one of the most promising avenues for advances in diagnosis, prevention and treatment of human disease. From principles, methodology and translational approaches to genome discoveries and clinical applications, Essentials of Genomic and Personalized Medicine will be a valuable resource for various professionals and students across medical disciplines, including human genetics and genomics, oncology, neuroscience, gene therapy, molecular medicine, pharmacology, and biomedical sciences. Updates with regard to diagnostic testing, pharmacogenetics, predicting disease susceptibility, and other important research components as well as chapters dedicated to cardiovascular disease, oncology, inflammatory disease, metabolic disease, neuropsychiatric disease, and infectious disease, present this book as an essential tool for a variety of professionals and students who are endeavouring into the developing the diverse and practical field of genomic and personalized medicine.
* Full color throughout
* Includes contributions on genetic counselling, ethical, legal/regulatory, and social issues related to the practice of genomic medicine from leaders in the field
* Introductory chapter highlights differences between personalized and traditional medicine, promising areas of current research, and challenges to incorporate the latest research discoveries and practice
* Ancillary material includes case studies and lab questions which highlight the collaborative approach to the science

Autoren/Hrsg.

Ginsburg, Geoffrey S.

Willard, Huntington F

Inhaltsverzeichnis

1;Front Cover;1
2;Essentials of Genomic and Personalized Medicine;4
3;Copyright Page;5
4;Table of Contents;6
5;Preface;10
6;Abbreviations;12
7;Contributors;20
8;Chapter 1 The Foundations of Genomic and Personalized Medicine;22
8.1;GENOMIC AND PERSONALIZED MEDICINE;22
8.2;GENES, GENOMES, AND DISEASE;25
8.3;FROM THE GENOME TO PERSONALIZED MEDICINE;26
8.4;CHALLENGES IN THE TRANSLATION OF GENOMICS TO HUMAN HEALTH;27
8.5;THE FUTURE OF PERSONALIZED MEDICAL CARE;28
8.6;REFERENCES;29
9;SECTION 1 BASICS;32
9.1;Chapter 2 Organization, Variation and Expression of the Human Genome;34
9.1.1;INTRODUCTION;34
9.1.2;THE HUMAN GENOME;35
9.1.3;VARIATION IN THE HUMAN GENOME;37
9.1.4;EXPRESSION OF THE HUMAN GENOME;40
9.1.5;GENOME SEQUENCING;41
9.1.6;REFERENCES;44
9.1.7;RECOMMENDED RESOURCES;47
9.2;Chapter 3 DNA Sequencing for the Detection of Human Genome Variation;48
9.2.1;INTRODUCTION;48
9.2.2;DNA SEQUENCING;49
9.2.3;ACKNOWLEDGEMENTS;57
9.2.4;REFERENCES;57
9.3;Chapter 4 Genome-Wide Association Studies and Genotyping Technologies;59
9.3.1;INTRODUCTION;59
9.3.2;PRINCIPLES OF GENOME-WIDE ASSOCIATION STUDIES;59
9.3.3;PLATFORM OVERVIEW;61
9.3.4;REFERENCES;65
9.4;Chapter 5 Copy Number Variation and Human Health;67
9.4.1;INTRODUCTION;67
9.4.2;BASIC PRINCIPLES OF CNVs;67
9.4.3;DETECTING CNVs IN A GENOME-WIDE MANNER;71
9.4.4;ASSOCIATION OF CNVs WITH DISEASE AND DISEASE SUSCEPTIBILITY;73
9.4.5;IMPLICATIONS OF CNVs;75
9.4.6;ACKNOWLEDGEMENTS;79
9.4.7;REFERENCES;79
9.4.8;RECOMMENDED RESOURCES;80
9.5;Chapter 6 DNA Methylation Analysis: Providing New Insight into Human Disease;81
9.5.1;INTRODUCTION;81
9.5.2;TECHNOLOGY TO ASSESS DNA METHYLATION;82
9.5.3;CLINICAL IMPACT OF DNA METHYLATION ANALYSIS;86
9.5.4;REFERENCES;90
9.5.5;RECOMMENDED RESOURCES;93
9.6;Chapter 7 DNA Microarrays in Biological Discovery and Patient Care;94
9.6.1;INTRODUCTION;94
9.6.2;MICROARRAY TECHNOLOGY;94
9.6.3;DATA ANALYSIS;97
9.6.4;APPLICATIONS;98
9.6.5;LIMITATIONS AND CHALLENGES;101
9.6.6;FUTURE DIRECTIONS;102
9.6.7;REFERENCES;105
9.6.8;RECOMMENDED RESOURCES;109
9.7;Chapter 8 Proteomics: The Deciphering of the Functional Genome;110
9.7.1;INTRODUCTION;110
9.7.2;GEL-BASED AND SOLUTION-BASED PROTEOMICS;111
9.7.3;MASS SPECTROMETRY;112
9.7.4;BIOINFORMATICS;113
9.7.5;IMPACT OF PROTEOMICS ON UNDERSTANDING DISEASES;115
9.7.6;ACKNOWLEDGEMENTS;117
9.7.7;REFERENCES;117
9.7.8;RECOMMENDED RESOURCES;117
9.8;Chapter 9 Comprehensive Metabolic Analysis for Understanding of Disease;118
9.8.1;INTRODUCTION;118
9.8.2;CURRENT METABOLOMICS PLATFORMS: BASIC TOOLS AND GENERAL FEATURES;119
9.8.3;COMPARISON OF NMR AND MS TECHNOLOGIES FOR UNBIASED METABOLIC PROFILING;120
9.8.4;MS METHODS FOR TARGETED METABOLIC PROFILING;121
9.8.5;EXAMPLES OF NMR-BASED METABOLIC PROFILING IN DISEASE RESEARCH;122
9.8.6;EXAMPLES OF TARGETED MS-BASED METABOLIC PROFILING FOR UNDERSTANDING OF DISEASE MECHANISMS;122
9.8.7;REFERENCES;126
10;SECTION 2 INFORMATICS;130
10.1;Chapter 10 Bioinformatic and Computational Analysis for Genomic Medicine;132
10.1.1;INTRODUCTION;132
10.1.2;VIGNETTES: HOW SPECIFIC BIOINFORMATICS METHODS CAN CHANGE THE PRACTICE OF MEDICINE;133
10.1.3;ANALYTIC METHODS;139
10.1.4;WHERE DATA FOR STUDIES MAY BE FOUND;140
10.1.5;BIOINFORMATICS VOCABULARIES AND ONTOLOGIES;141
10.1.6;FREELY AVAILABLE BIOINFORMATICS TOOLS;142
10.1.7;ACKNOWLEDGEMENTS;147
10.1.8;REFERENCES;147
10.1.9;RECOMMENDED RESOURCES;151
10.2;Chapter 11 Systems Biology and Systems Medicine;152
10.2.1;INTRODUCTION;152
10.2.2;SYSTEMS SCIENCE IN BIOLOGY AND MEDICINE;153
10.2.3;MULTI-PARAMETER BLOOD-BOURNE BIOMARKERS;154
10.2.4;EMERGING IN VIVO AND IN VITRO TECHNOLOGIES;155
10.2.5;COMPUTATIONAL AND MATHEMATICAL CHALLENGES IN SYSTEMS MEDICINE;158
10.2.6;REFERENCES;160
10.2.7;RECOMMENDED RESOURCES;162
10.3;Chapter 12 Electronic Medical Records in Genomic Medicine Practice and Research;163
10.3.1;INTRODUCTION;163
10.3.2;EMRs AND GENOMIC MEDICINE CLINICAL PRACTICE;164
10.3.3;EMRs AND GENOMIC MEDICINE RESEARCH;166
10.3.4;ACKNOWLEDGEMENTS;170
10.3.5;REFERENCES;170
10.3.6;RECOMMENDED RESOURCES;171
10.4;Chapter 13 Online Health Information Retrieval by Consumers;172
10.4.1;INTRODUCTION;172
10.4.2;CHARACTERISTICS OF CONSUMER SEARCHES FOR HEALTH INFORMATION;172
10.4.3;WHAT AND WHERE ARE CONSUMERS SEARCHING?;173
10.4.4;PERSONALIZED GENOMICS FOR CONSUMERS;175
10.4.5;REFERENCES;179
10.4.6;WIKIPEDIA REFERENCES;180
11;SECTION 3 TRANSLATIONAL;182
11.1;Chapter 14 Translational Genomics: From Discovery to Clinical Practice;184
11.1.1;INTRODUCTION;184
11.1.2;A ROADMAP FOR TRANSLATION;185
11.1.3;WHERE CAN GENOMICS HAVE IMPACT IN THE CONTINUUM OF HEALTH AND DISEASE?;185
11.1.4;TRANSLATIONAL GENOMICS: ENABLING COMPETENCIES;186
11.1.5;DEVELOPING ENVIRONMENTS THAT FOSTER TRANSLATIONAL GENOMICS TO HEALTH APPLICATIONS;190
11.1.6;REFERENCES;194
11.2;Chapter 15 Pharmacogenetics and Pharmacogenomics;196
11.2.1;INTRODUCTION;196
11.2.2;PHARMACOGENETIC STUDIES: FROM CONCEPT TO PRACTICE;198
11.2.3;MARKER SELECTION – STRATEGY AND APPLICATION;200
11.2.4;FROM BENCH TO BEDSIDE: INTEGRATION OF PHARMACOGENETIC TESTING INTO CLINICAL PRACTICE;203
11.2.5;EXAMPLES OF PGx TESTS: PROMISING NEW DEVELOPMENTS AND MARKETED PRODUCTS;204
11.2.6;FUTURE DEVELOPMENTS REQUIRED FOR THE FIELD TO FULLY MEET ITS EXPECTATIONS;206
11.2.7;REFERENCES;209
11.2.8;RECOMMENDED RESOURCES;211
11.3;Chapter 16 Clinical Implementation of Translational Genomics;212
11.3.1;INTRODUCTION;212
11.3.2;GENETIC STRATIFICATION WILL ALLOW MEDICAL CARE TO BE INDIVIDUALIZED AFTER A DIAGNOSIS IS MADE;212
11.3.3;POPULATION-BASED GERMLINE GENOMIC SCREENING;213
11.3.4;NEWBORN SCREENING;214
11.3.5;SOMATIC GENOMIC VARIATION;215
11.3.6;NOVEL SOURCES OF GENOMIC VARIATION;215
11.3.7;LABORATORY STANDARDS TO ENSURE ANALYTIC VALIDITY;215
11.3.8;CLINICAL VALIDATION AND CLINICAL UTILITY;216
11.3.9;COST;217
11.3.10;REIMBURSEMENT;217
11.3.11;WHO WILL PROVIDE GENOMIC MEDICAL CARE?;217
11.3.12;GENOMIC LITERACY;218
11.3.13;ACKNOWLEDGEMENTS;220
11.3.14;REFERENCES;220
11.3.15;RECOMMENDED RESOURCES;221
11.4;Chapter 17 The Role of Genomics in Enabling Prospective Health Care;222
11.4.1;INTRODUCTION;222
11.4.2;PREDICTIVE MODELS;224
11.4.3;PREDICTIVE FACTORS;224
11.4.4;ACKNOWLEDGEMENTS;228
11.4.5;REFERENCES;228
11.4.6;RECOMMENDED RESOURCES;229
11.5;Chapter 18 Genome Policy Considerations for Genomic Medicine;230
11.5.1;INTRODUCTION;230
11.5.2;GENOME RESEARCH AFTER THE HUMAN GENOME PROJECT;231
11.5.3;POLICY ISSUES IN LARGE-SCALE GENETICS AND GENOMICS RESEARCH;232
11.5.4;INTEGRATING GENOMIC MEDICINE APPLICATIONS IN HEALTHCARE;234
11.5.5;REFERENCES;239
11.6;Chapter 19 Federal Regulation of Genomic Medicine;244
11.6.1;INTRODUCTION;244
11.6.2;REGULATION OF GENOMIC TESTS;246
11.6.3;PHARMACOGENOMICS IN DRUG DEVELOPMENT AND CLINICAL MEDICINE: THE ROLE OF REGULATION;248
11.6.4;REFERENCES;252
11.6.5;RECOMMENDED RESOURCES;253
11.7;Chapter 20 Economic Issues and Genomic Medicine;254
11.7.1;INTRODUCTION;254
11.7.2;ECONOMIC EVALUATION AND COST-EFFECTIVENESS ANALYSIS;254
11.7.3;EVALUATING GENOMIC TECHNOLOGIES;256
11.7.4;ECONOMIC INCENTIVES AND THE FUTURE OF GENOMIC MEDICINE;258
11.7.5;ESTABLISHING VALUE-BASED REIMBURSEMENT FOR GENOMIC TECHNOLOGIES;260
11.7.6;ECONOMIC CHALLENGES;261
11.7.7;REFERENCES;264
11.8;Chapter 21 Public Health Genomics;266
11.8.1;INTRODUCTION;266
11.8.2;THE DEFINITION OF PUBLIC HEALTH GENOMICS;266
11.8.3;KEY CONCEPTS IN PUBLIC HEALTH GENOMICS;267
11.8.4;THE “ENTERPRISE” OF PUBLIC HEALTH GENOMICS;268
11.8.5;CORE ACTIVITIES IN PUBLIC HEALTH GENOMICS;269
11.8.6;THE ROLE OF PUBLIC HEALTH IN THE TRANSLATION OF HUMAN GENOME DISCOVERIES INTO HEALTH APPLICATIONS;271
11.8.7;THE FOCUS ON DISEASE PREVENTION AND HEALTH PROMOTION;271
11.8.8;REFERENCES;274
11.8.9;RECOMMENDED RESOURCES;276
12;SECTION 4 CLINICAL (CARDIOLOGY);278
12.1;Chapter 22 The Genomics of Hypertension;280
12.1.1;INTRODUCTION;280
12.1.2;PREDISPOSITION;281
12.1.3;DIAGNOSIS;283
12.1.4;PROGNOSIS;284
12.1.5;PHARMACOGENOMICS;285
12.1.6;ACKNOWLEDGEMENTS;288
12.1.7;REFERENCES;288
12.1.8;RECOMMENDED RESOURCES;289
12.2;Chapter 23 Lipoprotein Disorders;290
12.2.1;INTRODUCTION;290
12.2.2;OVERVIEW OF LIPOPROTEIN METABOLISM;290
12.2.3;PLASMA LIPID AND LIPOPROTEIN LEVELS AND ATHEROSCLEROTIC CARDIOVASCULAR DISEASE;292
12.2.4;INHERITED BASIS FOR BLOOD LIPID TRAITS;292
12.2.5;SCREENING FOR LIPID DISORDERS;293
12.2.6;GENETICS OF LDL-C;293
12.2.7;GENETICS OF HDL-C;295
12.2.8;GENETICS OF TRIGLYCERIDES;298
12.2.9;GENETIC LIPID DISORDERS WITHOUT CURRENT PROVEN MOLECULAR ETIOLOGY;299
12.2.10;INFLUENCE OF LIPID-MODULATING MUTATIONS ON RISK OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE;299
12.2.11;FUTURE DIRECTIONS IN GENETICS AND GENOMICS OF LIPOPROTEINS;300
12.2.12;PHARMACOGENETICS OF LIPID-MODULATING THERAPIES;302
12.2.13;IMPLICATIONS OF GENOMICS OF LIPOPROTEIN METABOLISM FOR THE DEVELOPMENT OF NOVEL THERAPIES;302
12.2.14;CLINICAL RECOMMENDATIONS FOR GENETIC TESTING FOR LIPID DISORDERS;303
12.2.15;ACKNOWLEDGEMENTS;306
12.2.16;REFERENCES;306
12.2.17;RECOMMENDED RESOURCES;309
12.3;Chapter 24 Genomics of Myocardial Infarction;310
12.3.1;INTRODUCTION;310
12.3.2;PREDISPOSITION;310
12.3.3;SCREENING STRATEGIES;316
12.3.4;PROGNOSTIC IMPLICATIONS OF MI;317
12.3.5;PHARMACOGENOMICS OF MI;317
12.3.6;NOVEL AND EMERGING THERAPIES;318
12.3.7;REFERENCES;320
12.3.8;RECOMMENDED RESOURCES;323
12.4;Chapter 25 Acute Coronary Syndromes;324
12.4.1;INTRODUCTION;324
12.4.2;PREDISPOSITION;324
12.4.3;SCREENING;325
12.4.4;DIAGNOSIS;326
12.4.5;PROGNOSIS;329
12.4.6;ACKNOWLEDGEMENTS;331
12.4.7;REFERENCES;331
12.4.8;RECOMMENDED RESOURCES;333
12.5;Chapter 26 Heart Failure in the Era of Genomic Medicine;334
12.5.1;INTRODUCTION;334
12.5.2;PREDISPOSITION (GENETIC AND NON-GENETIC);334
12.5.3;SCREENING;335
12.5.4;PATHOPHYSIOLOGY;336
12.5.5;DIAGNOSIS;337
12.5.6;PROGNOSIS;338
12.5.7;PHARMACOGENOMICS;339
12.5.8;MONITORING;340
12.5.9;ACKNOWLEDGEMENTS;344
12.5.10;REFERENCES;344
12.6;Chapter 27 Genomic Assessment of Cardiac Transplant Rejection;347
12.6.1;INTRODUCTION;347
12.6.2;CARDIAC ALLOTRANSPLANTATION AS A DEFINITIVE THERAPY FOR END-STAGE HEART FAILURE;347
12.6.3;THE PROBLEM OF ALLOGRAFT REJECTION;348
12.6.4;IMMUNOSUPPRESSION STRATEGIES TO PREVENT REJECTION;348
12.6.5;CURRENT STRATEGIES FOR MONITORING TRANSPLANT REJECTION;349
12.6.6;THE CARGO CLINICAL STUDY;351
12.6.7;DEVELOPMENT OF A GENE EXPRESSION SIGNATURE FOR CARDIAC TRANSPLANT REJECTION;351
12.6.8;PATHWAYS MONITORED BY THE GEP (AlloMap™) TEST;352
12.6.9;VARIABILITY OF THE BIOPSY GOLD STANDARD AND RELATIONSHIP TO THE GEP (AlloMap™) SCORE;352
12.6.10;DISCORDANCE BETWEEN BIOPSY GRADE AND MOLECULAR SCORE;352
12.6.11;EFFECT OF TIME POST-TRANSPLANTATION ON PERFORMANCE OF THE GEP TEST;353
12.6.12;RELATIONSHIP OF GEP SCORE TO CORTICOSTEROID DOSE;353
12.6.13;PREDICTION OF FUTURE ACR BY MOLECULAR SCORE;353
12.6.14;CLINICAL USE OF THE AlloMap™ TEST;354
12.6.15;REFERENCES;355
12.7;Chapter 28 Genetics and Genomics of Hypertrophic Cardiomyopathy;357
12.7.1;INTRODUCTION;357
12.7.2;DEFINITIONS, CLINICAL PRESENTATION, AND DIAGNOSIS;357
12.7.3;MOLECULAR GENETICS OF HCM;359
12.7.4;SCREENING AND TREATMENT FOR HCM;363
12.7.5;REFERENCES;367
12.8;Chapter 29 Genetics and Genomics of Arrhythmias;371
12.8.1;INTRODUCTION;371
12.8.2;SPECIFIC CARDIAC ARRHYTHMIAS;371
12.8.3;PRIMARY ABNORMALITIES IN CARDIAC RHYTHM: VENTRICULAR TACHYARRHYTHMIAS;371
12.8.4;COMPLEX FORMS OF LQTS;378
12.8.5;SHORT QT INTERVAL SYNDROME;382
12.8.6;FAMILIAL VT/CPVT;382
12.8.7;PRIMARY CONDUCTION ABNORMALITIES;383
12.8.8;REFERENCES;387
12.9;Chapter 30 Genetics and Genomics in the Management of Hemostasis and Thrombosis;395
12.9.1;INTRODUCTION;395
12.9.2;GENETICS OF COAGULATION;395
12.9.3;HUMAN HEMOSTATIC VARIABILITY;397
12.9.4;GENOTYPE–PHENOTYPE INFLUENCES;397
12.9.5;GENE-ENVIRONMENT INFLUENCES ON HEMOSTASIS;398
12.9.6;CIRCULATING CELLULAR AND PROTEIN INFLUENCES ON HEMOSTASIS AND THROMBOSIS;399
12.9.7;LINKAGE STUDIES IN THROMBOSIS;400
12.9.8;ASSOCIATION STUDIES IN THROMBOSIS;401
12.9.9;HERITABILITY AND THROMBOSIS: EXISTING COMPLEXITIES;401
12.9.10;A PERSONALIZED APPROACH TO HEMOSTASIS AND THROMBOSIS;401
12.9.11;PATIENT SCREENING: A TRADITIONAL PARADIGM;401
12.9.12;PATIENT SCREENING: A COMPREHENSIVE AND POPULATION-BASED APPROACH;402
12.9.13;PROGNOSTIC CONSIDERATIONS;403
12.9.14;EMERGING PLATFORM FOR HEMOSTASIS AND THROMBOSIS RESEARCH;405
12.9.15;REFERENCES;409
12.10;Chapter 31 Genomics of Congenital Heart Disease;411
12.10.1;INTRODUCTION;411
12.10.2;CHD GENE DISCOVERY BY CONVENTIONAL GENETICS;411
12.10.3;GENOMIC STRATEGIES FOR CHD GENE DISCOVERY;416
12.10.4;CYTOGENETIC AND MOLECULAR GENETIC TESTING;417
12.10.5;MEDICAL EVALUATION AND COUNSELING RECOMMENDATIONS;418
12.10.6;ACKNOWLEDGEMENTS;421
12.10.7;REFERENCES;421
12.10.8;RECOMMENDED RESOURCES;423
13;SECTION 5 CLINICAL (ONCOLOGY);426
13.1;Chapter 32 Genomics in the Management of Lymphomas;428
13.1.1;INTRODUCTION;428
13.1.2;DIFFUSE LARGE B-CELL LYMPHOMA;431
13.1.3;PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA;432
13.1.4;HODGKIN LYMPHOMA;433
13.1.5;FOLLICULAR LYMPHOMA;434
13.1.6;MANTLE CELL LYMPHOMA;436
13.1.7;BURKITT LYMPHOMA;436
13.1.8;REFERENCES;438
13.2;Chapter 33 Genomics in Leukemias;442
13.2.1;INTRODUCTION;442
13.2.2;GENOMICS IN LEUKEMIAS: INSIGHTS INTO LEUKEMIA BIOLOGY;444
13.2.3;GENOMICS IN LEUKEMIAS: EVALUATION OF DRUG EFFECTS;445
13.2.4;GENOMICS IN LEUKEMIAS: CLINICAL OUTCOME PREDICTION;447
13.2.5;ACKNOWLEDGMENTS;450
13.2.6;REFERENCES;450
13.2.7;RECOMMENDED RESOURCES;452
13.3;Chapter 34 Genomics in the Diagnosis and Management of Lung Cancer;453
13.3.1;INTRODUCTION;453
13.3.2;EARLY DIAGNOSIS/SCREENING OF LUNG CANCER;454
13.3.3;CLASSIFICATION AND PROGNOSIS;456
13.3.4;PATHOGENESIS AND TREATMENT OF LUNG CANCER;459
13.3.5;REFERENCES;464
13.3.6;RECOMMENDED RESOURCE;466
13.4;Chapter 35 Genomics in the Diagnosis and Management of Breast Cancer;467
13.4.1;INTRODUCTION;467
13.4.2;THE PROMISE;467
13.4.3;GENETIC BASES;469
13.4.4;MOLECULAR BASES;469
13.4.5;PROGNOSIS AND PREDICTION;470
13.4.6;MOLECULAR MARKERS;470
13.4.7;GENOMIC INSIGHTS;471
13.4.8;NETHERLANDS CANCER INSTITUTE STUDY;471
13.4.9;DUKE-TAIPEI STUDY;473
13.4.10;NSABP STUDY;473
13.4.11;PATHWAY PREDICTION;474
13.4.12;THE REALITY OF CLINICAL GENOMICS;474
13.4.13;REFERENCES;476
13.5;Chapter 36 Colorectal Cancer;478
13.5.1;INTRODUCTION;478
13.5.2;GENOMIC MODEL OF CRC;479
13.5.3;PREDISPOSITION FOR CRC;481
13.5.4;RISK ASSESSMENT, EVALUATION, AND GENETIC TESTING;486
13.5.5;SCREENING AND SURVEILLANCE;488
13.5.6;PROGNOSIS AND TREATMENT;488
13.5.7;PHARMACOGENETICS/GENOMICS OF CHEMOPREVENTION AND CHEMOTHERAPY;489
13.5.8;REFERENCES;492
13.6;Chapter 37 Genomic Evaluation and Management of Prostate Cancer;498
13.6.1;INTRODUCTION;498
13.6.2;GENETIC PREDISPOSITION AND ALTERATIONS IN PROSTATE CANCER;498
13.6.3;PROSTATE CANCER DETECTION;501
13.6.4;GENOMIC CHANGES ASSOCIATED WITH PROSTATE CANCER BEHAVIOR;504
13.6.5;GENOMIC CHANGES ASSOCIATED WITH HORMONE-REFRACTORY PROSTATE CANCER;506
13.6.6;REFERENCES;509
13.7;Chapter 38 Genomic Assessment of Ovarian Cancer;514
13.7.1;INTRODUCTION;514
13.7.2;INHERITED OVARIAN CANCER SYNDROMES;514
13.7.3;OPTIONS FOR SCREENING AND PREVENTION;515
13.7.4;GENOMIC INSTABILITY AND OVARIAN CANCER;515
13.7.5;SOMATIC MUTATIONS IN OVARIAN CANCER;515
13.7.6;ONCOGENES AND GROWTH FACTORS;516
13.7.7;TUMOR SUPPRESSOR GENES;517
13.7.8;EPIGENETICS IN OVARIAN CARCINOGENESIS;517
13.7.9;OVARIAN CANCER METASTASES;517
13.7.10;REFERENCES;520
13.8;Chapter 39 Genomic Evaluation of Pancreatic Neoplasms;522
13.8.1;INTRODUCTION;522
13.8.2;PREDISPOSITION (GENETIC AND NON-GENETIC);523
13.8.3;SCREENING;523
13.8.4;DIAGNOSIS;524
13.8.5;PROGNOSIS;526
13.8.6;REFERENCES;529
13.9;Chapter 40 Genomic Evaluation of Head and Neck Cancer;532
13.9.1;INTRODUCTION;532
13.9.2;HEAD AND NECK SQUAMOUS CELL CARCINOMA;532
13.9.3;GENOMICS OF HNSCC: CLINICAL APPLICATIONS;538
13.9.4;REFERENCES;540
13.9.5;RECOMMENDED RESOURCES;542
13.10;Chapter 41 Genomic Evaluation of Brain Tumors and Gliomas;543
13.10.1;INTRODUCTION;543
13.10.2;PREDISPOSITION;544
13.10.3;DIAGNOSIS AND PROGNOSIS;545
13.10.4;PHARMACOGENOMICS;548
13.10.5;SUMMARY;548
13.10.6;REFERENCES;550
13.11;Chapter 42 Targeted Therapies for Cancer;553
13.11.1;INTRODUCTION;553
13.11.2;TARGETED THERAPIES FOR CANCER;553
13.11.3;THE IDEAL TARGET;553
13.11.4;THE FIRST DIAGNOSTIC-THERAPEUTIC COMBINATION IN CANCER THERAPY: HORMONAL THERAPY FOR BREAST CANCER;554
13.11.5;DIAGNOSTIC-THERAPEUTIC COMBINATIONS FOR LEUKEMIA AND LYMPHOMA;554
13.11.6;HER-2 POSITIVE BREAST CANCER AND TRASTUZUMAB (HERCEPTIN®);555
13.11.7;OTHER TARGETED ANTICANCER THERAPIES USING ANTIBODIES;556
13.11.8;SELECTED TARGETED ANTICANCER THERAPIES USING SMALL MOLECULES;561
13.11.9;REFERENCES;565
14;SECTION 6 CLINICAL (INFLAMMATORY DISEASE);570
14.1;Chapter 43 Genomics in the Evaluation and Management of Rheumatoid Arthritis;572
14.1.1;INTRODUCTION;572
14.1.2;PREDISPOSITION;573
14.1.3;SCREENING;578
14.1.4;DIAGNOSIS, PROGNOSIS, AND MONITORING;579
14.1.5;REFERENCES;582
14.2;Chapter 44 Genomic Evaluation of Multiple Sclerosis;587
14.2.1;INTRODUCTION;587
14.2.2;GENOMICS IN MS;587
14.2.3;TRANSCRIPTOMICS IN MS;589
14.2.4;IMMUNOMICS IN MS;590
14.2.5;PROTEOMICS IN MS;591
14.2.6;REFERENCES;593
14.3;Chapter 45 Genomic Assessment of Inflammatory Bowel Disease;596
14.3.1;INTRODUCTION;596
14.3.2;PREDISPOSITION (GENETIC AND NON-GENETIC);597
14.3.3;SCREENING;599
14.3.4;DIAGNOSIS;600
14.3.5;PROGNOSIS;601
14.3.6;PHARMACOGENOMICS;603
14.3.7;REFERENCES;606
14.4;Chapter 46 Asthma Genomics;611
14.4.1;INTRODUCTION;611
14.4.2;ASTHMA: BASIC PATHOBIOLOGY;611
14.4.3;PREDISPOSITION (GENETIC AND NON-GENETIC) TO ASTHMA;612
14.4.4;GENOME-WIDE LINKAGE ANALYSES OF ASTHMA AND ITS INTERMEDIATE PHENOTYPES;612
14.4.5;CANDIDATE-GENE ASSOCIATION STUDIES OF ASTHMA;614
14.4.6;GENOME-WIDE ASSOCIATION STUDIES OF ASTHMA;615
14.4.7;ASTHMA GENOMICS;615
14.4.8;PHARMACOGENETICS;615
14.4.9;ACKNOWLEDGEMENTS;619
14.4.10;REFERENCES;619
14.4.11;RECOMMENDED RESOURCE;623
14.5;Chapter 47 Genomics in the Evaluation and Management of Chronic Obstructive Pulmonary Disease;624
14.5.1;INTRODUCTION;624
14.5.2;PREDISPOSITION;624
14.5.3;PATHOPHYSIOLOGY;625
14.5.4;CELLULAR AND MOLECULAR MECHANISMS;627
14.5.5;DIAGNOSIS AND SCREENING;630
14.5.6;PROGNOSIS;631
14.5.7;MANAGEMENT;631
14.5.8;REFERENCES;635
14.6;Chapter 48 Genetics and Genomics of Interstitial Lung Disease;637
14.6.1;INTRODUCTION;637
14.6.2;GENETIC DETERMINANTS OF SARCOIDOSIS;638
14.6.3;SURFACTANT PROTEINS AND DPLD;640
14.6.4;GENETIC DETERMINANTS OF PULMONARY FIBROSIS IDENTIFIED IN RARE INHERITED DISORDERS;641
14.6.5;GENETIC DETERMINANTS OF FIP;641
14.6.6;REFERENCES;645
14.7;Chapter 49 Peptic Ulcer Disease;648
14.7.1;INTRODUCTION;648
14.7.2;PATHOPHYSIOLOGY OF ULCER FORMATION;649
14.7.3;THE HELICOBACTER GENOME;650
14.7.4;HUMAN POLYMORPHISM AND PUD;656
14.7.5;GENOMICS IN THE MANAGEMENT OF DISEASE;656
14.7.6;ACKNOWLEDGEMENTS;659
14.7.7;REFERENCES;659
14.7.8;RECOMMENDED RESOURCES;663
15;SECTION 7 CLINICAL (METABOLIC DISEASE);664
15.1;Chapter 50 Genomics in Pathogenesis of Cirrhosis;666
15.1.1;INTRODUCTION;666
15.1.2;FIBROSIS AND CIRRHOSIS;666
15.1.3;DIAGNOSIS OF CIRRHOSIS;667
15.1.4;GENETICS OF CIRRHOSIS;667
15.1.5;THE LIVER TRANSCRIPTOME;669
15.1.6;THE LIVER PROTEOME;670
15.1.7;DEVELOPMENT OF LIVER FIBROSIS;670
15.1.8;TRANSCRIPTOME ANALYSIS OF LIVER DISEASE;672
15.1.9;PROTEOMIC STUDIES OF LIVER DISEASE;674
15.1.10;PROTEOMICS IN OTHER LIVER DISEASE;676
15.1.11;REFERENCES;678
15.2;Chapter 51 Genomic Medicine and Obesity;682
15.2.1;INTRODUCTION;682
15.2.2;OBESITY: CAUSES AND GENETIC PREDISPOSITION;682
15.2.3;SEARCH FOR GENES INVOLVED IN OBESITY;684
15.2.4;DIAGNOSIS AND CHARACTERIZATION OF GENES ASSOCIATED WITH OBESITY;685
15.2.5;SCREENING AND DIAGNOSIS;689
15.2.6;PROGNOSIS AND GENE-BASED TREATMENTS;690
15.2.7;ACKNOWLEDGEMENTS;694
15.2.8;REFERENCES;694
15.3;Chapter 52 Diabetes;697
15.3.1;INTRODUCTION;697
15.3.2;GWAS IN TYPE 2 DIABETES;698
15.3.3;FUTURE RESEARCH IN TYPE 2 DIABETES GENETICS;700
15.3.4;GWAS IN TYPE 1 DIABETES;701
15.3.5;FUTURE STUDIES IN TYPE 1 DIABETES;702
15.3.6;CLINICAL UTILITY OF GENETIC RESEARCH IN DIABETES;702
15.3.7;REFERENCES;703
16;SECTION 8 CLINICAL (NEUROLOGICAL DISEASE);706
16.1;Chapter 53 Genetics and Genomics of Dementia;708
16.1.1;INTRODUCTION;708
16.1.2;INCIDENCE OF DEMENTIA;709
16.1.3;PRIMARY DEMENTIAS;710
16.1.4;CLINICAL APPROACH TO THE DEMENTIAS;715
16.1.5;REFERENCES;717
16.1.6;RECOMMENDED RESOURCES;720
16.2;Chapter 54 Genetics and Genomics of Parkinson's Disease;721
16.2.1;INTRODUCTION;721
16.2.2;CLINICAL CHARACTERISTICS OF PD;721
16.2.3;GENETICS OF PD;723
16.2.4;GENETICS OF SPORADIC PD;726
16.2.5;REFERENCES;730
16.2.6;RECOMMENDED RESOURCES;732
16.3;Chapter 55 Genomic Considerations in Ophthalmology;733
16.3.1;INTRODUCTION;733
16.3.2;LENS;736
16.3.3;IRIS;736
16.3.4;TRABECULAR MESHWORK;736
16.3.5;OPTIC NERVE;737
16.3.6;RETINA;737
16.3.7;GENETIC TESTING FOR OCULAR DISORDERS;738
16.3.8;REFERENCES;740
16.4;Chapter 56 Genomics in the Diagnosis and Management of Depression;743
16.4.1;INTRODUCTION;743
16.4.2;DIAGNOSIS, PREVALENCE AND COURSE OF DEPRESSION;743
16.4.3;PATHOPHYSIOLOGICAL MECHANISMS;744
16.4.4;PHARMACOGENOMICS OF ANTIDEPRESSANTS;747
16.4.5;GENE AND PROTEIN EXPRESSION STUDIES;748
16.4.6;FUTURE CONSIDERATIONS;748
16.4.7;REFERENCES;750
17;SECTION 9 CLINICAL (INFECTIOUS DISEASE);752
17.1;Chapter 57 Genomic Approaches to the Host Response to Pathogens;754
17.1.1;INTRODUCTION;754
17.1.2;GENETIC SUSCEPTIBILITY TO PATHOGENS;755
17.1.3;EXPLORING THE HOST RESPONSE THROUGH EXPRESSION PROFILING;757
17.1.4;ACKNOWLEDGEMENT;761
17.1.5;REFERENCES;761
17.1.6;RECOMMENDED RESOURCES;764
17.2;Chapter 58 Host Genomics and Bacterial Infections;765
17.2.1;INTRODUCTION;765
17.2.2;GENOMICS AND THE STUDY OF BACTERIAL INFECTIONS;765
17.2.3;HOST GENOMICS AND GRAM-POSITIVE, GRAM-NEGATIVE AND MYCOBACTERIAL INFECTIONS;769
17.2.4;REFERENCES;776
17.3;Chapter 59 Genomics in the Evaluation and Management of Sepsis;781
17.3.1;INTRODUCTION;781
17.3.2;GENETIC POLYMORPHISMS ASSOCIATED WITH SEPSIS;782
17.3.3;MOLECULAR SIGNATURES AND SEPSIS;787
17.3.4;REFERENCES;791
17.4;Chapter 60 Genomics and the Management of Hepatitis;795
17.4.1;INTRODUCTION;795
17.4.2;VIROLOGY OF HEPATITIS VIRUSES;795
17.4.3;ACQUISITION AND PREDISPOSITION TO VIRAL HEPATITIS;797
17.4.4;SCREENING AND DIAGNOSIS OF VIRAL HEPATITIS;798
17.4.5;PATHOGENESIS OF VIRAL HEPATITIS;799
17.4.6;THERAPEUTICS AND PHARMACOGENOMICS;802
17.4.7;REFERENCES;804
18;Index;808
18.1;A;808
18.2;B;812
18.3;C;813
18.4;D;819
18.5;E;821
18.6;F;822
18.7;G;824
18.8;H;826
18.9;I;829
18.10;J;831
18.11;K;831
18.12;L;831
18.13;M;834
18.14;N;837
18.15;O;838
18.16;P;839
18.17;Q;843
18.18;R;843
18.19;S;845
18.20;T;847
18.21;U;849
18.22;V;850
18.23;W;850
18.24;X;851
18.25;Y;851
18.26;Z;851