Genomic and Personalized Medicine, Two-Vol Set, Volume 1-2

**Volume 1** 
Cover......Page 1
Genomic and Personalized Medicine......Page 4
Copyright Page......Page 5
Table of Contents......Page 10
Foreword......Page 26
Preface......Page 28
Acknowledgements......Page 30
Abbreviations......Page 32
Advisory Board......Page 40
Contributors......Page 42
PART I: GENOMIC APPROACHES TO BIOLOGY AND MEDICINE......Page 50
Section 1 Principles of Human Genomics......Page 52
Introduction......Page 53
The Human Genome......Page 55
Variation in the Human Genome......Page 58
Expression of the Human Genome......Page 60
Genes, Genomes and Disease......Page 62
From Genome to Personalized Medicine......Page 64
References......Page 67
Recommended Resources......Page 70
Important Concepts in Population Genomics......Page 71
Human Population Genomics......Page 75
Application of Population Genomics to Genomic Medicine......Page 77
Conclusions......Page 78
References......Page 79
Recommended Resources......Page 81
Identifying Common and Rare Genomic Variations in the Population......Page 82
Relating DNA Variation to Phenotypes......Page 85
Integration of "Omic" Technologies with Genetics......Page 89
References......Page 92
Recommended Resources......Page 95
Introduction......Page 96
Importance of the Environment......Page 97
The Environmental Genome Project......Page 99
Problematic Nature of Gene–environment Interaction Studies......Page 101
Polymorphism and Disease Susceptibility: Case–control Studies......Page 102
Epigenetics and the Environment......Page 105
References......Page 106
Introduction......Page 109
DNA Methylation Patterns......Page 110
Chromatin Modification......Page 112
DNA Methylation and Chromatin States Co-operatively Determine the State of Activity of Genes......Page 114
Epigenetics and Human Disease......Page 116
Conclusions......Page 118
References......Page 119
Introduction......Page 123
Systems Science in Biology And Medicine......Page 124
Multi-parameter Blood-bourne Biomarkers......Page 125
Emerging in vivo and in vitro Technologies......Page 127
Conclusions and Perspectives......Page 130
References......Page 131
Recommended Resources......Page 134
Section 2 Technology Platforms for Genomic Medicine......Page 136
Introduction......Page 137
DNA Sequencing......Page 138
Other Methodologies for Polymorphism Detection......Page 144
Future Directions......Page 145
References......Page 146
Principles of Genome-wide Association Studies......Page 150
Platform Overview......Page 152
References......Page 155
Basic Principles of CNVs......Page 157
Detecting CNVs in a Genome-wide Manner......Page 161
Association of CNVs to Disease and Disease Susceptibility......Page 163
Implications of CNVs......Page 165
References......Page 167
Recommended Resources......Page 168
Introduction......Page 169
Performing Comparative Sequence Analysis: Resources and Methods......Page 170
Comparative Sequence Analysis and Human Genetic Disease......Page 173
References......Page 177
Recommended Resources......Page 179
Introduction......Page 180
Technology to Assess DNA Methylation......Page 181
Clinical Impact of DNA Methylation Analysis......Page 185
References......Page 188
Recommended Resources......Page 191
Gene Expression Technology......Page 192
Gene Discovery......Page 195
Molecular Signature Analysis......Page 197
Current Issues in Gene Expression Analysis......Page 200
Conclusions......Page 202
References......Page 203
Recommended Resources......Page 205
Microarray Technology......Page 206
Data Analysis......Page 209
Applications......Page 210
Future Directions......Page 214
References......Page 217
Recommended Resources......Page 221
Introduction......Page 222
Gel-based and Solution-based Proteomics......Page 223
Mass Spectrometry......Page 224
Bioinformatics......Page 225
Conclusions......Page 227
Recommended Resources......Page 228
Introduction......Page 229
Current Metabolomics Platforms: Basic Tools and General Features......Page 230
Comparison of NMR and MS Technologies for Unbiased Metabolic Profiling......Page 231
MS Methods for Targeted Metabolic Profiling......Page 232
Examples of Targeted MS-based Metabolic Profiling for Understanding of Disease Mechanisms......Page 233
References......Page 238
Introduction......Page 242
RNA Interference......Page 243
Chemical Genomics......Page 246
Gene Function Studies......Page 248
Conclusions......Page 249
References......Page 250
Recommended Resources......Page 252
Section 3 Informatic and Computational Platforms for Genomic Medicine......Page 254
Introduction......Page 255
Vignettes: How Specific Bioinformatics Methods Can Change the Practice Of medicine......Page 256
Analytic Methods......Page 262
Where Data for Studies May be Found......Page 263
Bioinformatics Vocabularies and Ontologies......Page 264
Freely Available Bioinformatics Tools......Page 265
New Questions for Genomic Medicine......Page 269
References......Page 270
Recommend Resources......Page 274
Introduction......Page 275
Databases for Genomic Medicine......Page 276
Conclusion......Page 279
References......Page 280
Recommended Resources......Page 281
Introduction......Page 282
EMRs and Genomic Medicine Clinical Practice......Page 283
EMRs and Genomic Medicine Research......Page 285
References......Page 289
Recommended Resources......Page 290
Introduction......Page 291
CDS Background: History, Examples, Evidence of Effectiveness, and Desirable Attributes......Page 292
Potential Uses of CDS to Support Genomic and Personalized Medicine......Page 294
Limited Deployability: The Potential Achilles' Heel of CDS Systems for Genomic Medicine......Page 295
Challenges to Widespread Deployment of Effective CDS Systems......Page 296
References......Page 298
Recommended Resources......Page 300
Characteristics of Consumer Searches for Health Information......Page 301
What and Where Are Consumers Searching?......Page 302
Personalized Genomics for Consumers......Page 304
References......Page 305
Wikipedia References......Page 306
PART II: TRANSLATIONAL APPROACHES IN GENOMIC AND PERSONALIZED MEDICINE......Page 308
Section 4 Enabling Strategies in the Translation of Genomics into Medicine......Page 310
Introduction......Page 311
Where Can Genomics Have Impact in the Continuum of Health and Disease?......Page 312
The Genomics "Gold Rush"......Page 313
"Grand Challenges" in Translation of Genomics to Human Health......Page 315
Translational Genomics: Enabling Competencies......Page 316
How Are We Going to Do This? Developing Environments That Foster Translational Genomics to Health Applications......Page 319
References......Page 321
Introduction......Page 324
Principles of Experimental Design......Page 325
Design Issues in Genomic Medicine......Page 330
Recommended Resources......Page 332
Introduction......Page 333
The Evolving Face of Biobanking......Page 334
Existing Models: Biobanking in Europe and the USA......Page 335
Singapore's National Biobank and National Aspirations In Biomedical Research......Page 337
The Future of National Biobanks......Page 343
References......Page 345
Recommended Resources......Page 346
Biomarkers in Medicine......Page 348
Biomarkers of Exposure......Page 351
Biomarkers of Early Disease Risk......Page 352
Biomarkers of Genetic Susceptibility to Disease......Page 353
References......Page 355
Optimization of the Candidate Protein Research Assay......Page 357
Analytical Evaluation......Page 358
Pre-analytical Variation......Page 360
Clinical Evaluation......Page 361
Indicators of Diagnostic Accuracy And Predictability......Page 362
Design of Diagnostic Studies......Page 365
Assay Transfer to Diagnostic Company......Page 366
References......Page 367
Recommended Resources......Page 369
Introduction......Page 370
Pharmacogenetic Studies: From Concept to Practice......Page 372
Marker Selection – Strategy and Application......Page 374
From Bench to Bedside: Integration of Pharmacogenetic Testing into Clinical Practice......Page 377
Examples of PGx Tests: Promising New Developments and Marketed Products......Page 378
Future Developments Required for the Field to Fully Meet its Expectations......Page 380
References......Page 381
Recommended Resources......Page 383
The Drug Discovery Process......Page 384
Genomics in Target Discovery......Page 385
Pharmacogenomics and Drug Development......Page 386
Pharmacodynamic Markers and their Role in Drug Discovery and Development......Page 387
Genomics in Drug Approval and Regulation......Page 389
References......Page 390
Recommended Resources......Page 391
Introduction......Page 392
Methods for Identification of Genetic Classifiers......Page 393
Pharmacogenomics in the Drug Development Pipeline......Page 395
Efficacy Pharmacogenetics – here and Now......Page 397
Drug Exposure Pharmacogenetics to Tune Efficacy and Safety Profiles......Page 398
Investigation and Management of Safety in Clinical Trials......Page 399
"No Samples, No Science"......Page 401
Conclusions......Page 403
References......Page 404
Genetic Stratification Will Allow Medical Care to be Individualized After a Diagnosis is Made......Page 406
Population-based Germline Genomic Screening......Page 407
Newborn Screening......Page 408
Somatic Genomic Variation......Page 409
Laboratory Standards to Ensure Analytic Validity......Page 410
Cost......Page 411
Who Will Provide Genomic Medical Care?......Page 412
Ethical, Legal, and Social Issues......Page 413
References......Page 414
Recommended Resources......Page 415
Introduction......Page 416
Novel Diagnostics......Page 417
Conclusions: Translational Challenges for Innovative Diagnostics......Page 423
References......Page 424
Introduction......Page 427
Predictive Factors......Page 429
Risk Assessment for Breast Cancer......Page 431
Acknowledgements......Page 432
References......Page 433
Recommended Resources......Page 434
Section 5 Policy Challenges in Genomic and Personalized Medicine......Page 436
Introduction......Page 437
Genome Research after the Human Genome Project......Page 438
Policy Issues in Large-scale Genetics and Genomics Research......Page 440
Integrating Genomic Medicine Applications in Healthcare......Page 441
Conclusion......Page 445
References......Page 446
Introduction......Page 450
Genetic and Genomic Literacy of the Public and Makers of Public Policy......Page 451
Education of the Providers of Health Care......Page 453
References......Page 460
Introduction......Page 463
Regulation of Genomic Tests......Page 465
Pharmacogenomics in Drug Development And Clinical Medicine: the Role of Regulation......Page 467
Fda Efforts to Advance Genomic Product Development......Page 470
References......Page 471
Recommended Resources......Page 472
Economic Evaluation and Cost-effectiveness Analysis......Page 473
Evaluating Genomic Technologies......Page 475
Economic Incentives and the Future of Genomic Medicine......Page 477
Establishing Value-based Reimbursement For Genomic Technologies......Page 479
Conclusions......Page 480
References......Page 481
Introduction......Page 483
Landscape of Private Sector Genomics......Page 484
Future Trends......Page 490
References......Page 491
Section 6 Genomic Medicine and Public Health......Page 494
The Emergence of Public Health Genomics......Page 495
Key Concepts in Public Health Genomics......Page 496
The "Enterprise" of Public Health Genomics......Page 497
Core Activities in Public Health Genomics......Page 498
Moving Public Health Genomics Forward: Leadership And Networks......Page 500
References......Page 501
Recommended Resources......Page 502
The Continuum from Genetics to Genomics in Health Practice......Page 503
The Role of Public Health in the Translation of Human Genome Discoveries into Health Applications......Page 504
The Population Perspective: Crucial Role of Public Health Sciences......Page 506
Conclusion......Page 507
References......Page 508
Human Genome Epidemiology......Page 510
Epidemiologic Study Designs......Page 511
Epidemiologic Measures Of Disease Frequency, Association, and Risk......Page 512
Measurement and Bias......Page 513
Gene–environment Interaction......Page 514
Building the Evidence Base......Page 515
References......Page 516
Recommended Resources......Page 518
Introduction......Page 519
Screening Technology: Simple Ideas, Complex Realities......Page 520
Influence of Genetics and -omic Technologies on NBS......Page 525
References......Page 526
Recommended Resources......Page 528
Clinical Approach......Page 530
References......Page 537
Recommended Resources......Page 541
Section 7 Clinical Technologies Supporting Personalized Medicine......Page 542
Molecular Imaging and Cancer Detection......Page 543
Molecular Imaging to Determine Treatment Efficacy......Page 545
Near-term Needs and Opportunities......Page 546
References......Page 547
Physics......Page 549
Imaging Agents and Methods in Analysis of Biological Samples......Page 552
References......Page 559
Recommended Resources......Page 560
Introduction......Page 561
Basics of MRI Contrast......Page 562
MR Contrast Agents for Molecular Imaging Applications......Page 564
Molecular Imaging Applications of MRI......Page 566
Conclusions......Page 569
References......Page 570
Introduction......Page 573
Imaging Technology......Page 574
References......Page 579
Introduction......Page 581
Conceptual Basis of Imaging Genetics......Page 582
Basic Principles of Imaging Genetics......Page 583
Imaging Genetics and the Neurobiology of the 5-httlpr......Page 584
References......Page 585
Role of Viruses in Human Infectious Disease......Page 587
Microfabrication......Page 590
Nanofabrication......Page 601
Are there Additional Alternatives to Diagnostic Microarrays?......Page 602
References......Page 603
Recommended Resources......Page 609
Introduction......Page 611
The Genomic Era: From Microbial Genome to Vaccine Development......Page 612
Impact of Whole Genome Analyses......Page 613
In Vivo Gene Expression: Ivet And Stm......Page 615
Microarray Expression Technology......Page 616
From Microbial to Human Genome Sequencing: Genomic Medicine......Page 617
Metagenomics: Deciphering Host–microbe Interactions......Page 618
References......Page 619
Introduction......Page 622
Immune Suppression by Tumors and by Regulatory T-cells......Page 623
Molecularly Undefined Cancer Vaccines......Page 625
Peptides......Page 626
Proteins and Carbohydrates......Page 627
Nucleic Acids: Plasmid DNA and Messenger RNA......Page 628
Adjuvants, Formulations, and Route of Application......Page 631
Immunomonitoring......Page 632
References......Page 633
Introduction......Page 639
Biosensors for Detection of Oligonucleotides for the Detection of Disease......Page 640
Nucleic Acid as Tools for Biosensing......Page 641
Outlook......Page 645
References......Page 646
Types of Stem Cells: Embryonic and Adult Stem Cells......Page 648
How to Define The Molecular Signature of Stem Cells......Page 649
Future Directions to Identify the Global Integrated Regulatory Network......Page 650
Future Directions in Stem Cell Therapies......Page 653
References......Page 655
Introduction......Page 659
Gene Delivery Vehicles......Page 660
Gene Therapy Clinical Trials......Page 663
References......Page 666
 **Volume 2** 
Front Cover......Page 669
Genomic and Personalized Medicine......Page 672
Copyright Page......Page 673
Table of Contents......Page 678
Foreword......Page 694
Preface......Page 696
Acknowledgements......Page 698
Advisory Board......Page 700
Contributors......Page 702
Part III: Disease-Based Genomic and Personalized Medicine: Genome Discoveries and Clinical Applications......Page 710
Section 8 Cardiovascular Genomic Medicine......Page 712
Introduction......Page 713
Predisposition......Page 714
Diagnosis......Page 716
Prognosis......Page 717
Pharmacogenomics......Page 719
Conclusion......Page 720
References......Page 721
Recommended Resources......Page 722
Overview of Lipoprotein Metabolism......Page 723
Inherited Basis for Blood Lipid Traits......Page 725
Genetics of Ldl-c......Page 726
Genetics of Hdl-c......Page 728
Genetics of Triglycerides......Page 731
Influence of Lipid-modulating Mutations on Risk of Atherosclerotic Cardiovascular Disease......Page 732
Future Directions in Genetics and Genomics of Lipoproteins......Page 733
Implications of Genomics of Lipoprotein Metabolism For The Development of Novel Therapies......Page 735
Clinical Recommendations for Genetic Testing for Lipid Disorders......Page 736
References......Page 737
Recommended Resources......Page 740
Sources of ROS in vascular cells......Page 741
ROS-induced inflammatory gene expression in vascular cells......Page 742
Association of ROS modulators with atherosclerosis......Page 743
ROS-regulated signaling pathways......Page 744
Regulation of transcription factors by ROS......Page 745
Inhibitors of ROS signaling and vascular disease......Page 747
Conclusion......Page 748
References......Page 749
Predisposition......Page 754
Screening Strategies......Page 761
Pharmacogenomics of MI......Page 762
Novel and Emerging Therapies......Page 763
Conclusion......Page 764
References......Page 765
Recommended Resources......Page 768
Predisposition......Page 769
Screening......Page 770
Diagnosis......Page 771
Prognosis......Page 774
Pharmacogenomics......Page 775
Acknowledgements......Page 776
References......Page 777
Recommended Resources......Page 779
Predisposition (Genetic and Non-genetic)......Page 781
Screening......Page 782
Pathophysiology......Page 783
Diagnosis......Page 784
Prognosis......Page 785
Pharmacogenomics......Page 786
Monitoring......Page 787
Novel Therapeutics and Future Directions......Page 790
Conclusions and Recommendations......Page 791
References......Page 792
Cardiac Allotransplantation as a Definitive Therapy for End-stage Heart Failure......Page 794
Immunosuppression Strategies to Prevent Rejection......Page 795
Current Strategies for Monitoring Transplant Rejection......Page 796
Development of a Gene Expression Signature For Cardiac Transplant Rejection......Page 798
Discordance Between Biopsy Grade and Molecular Score......Page 799
Relationship of Gep Scores to Cytomegalovirus Infection......Page 800
Clinical Use of the Allomap™ Test......Page 801
Further Application of Genomic Science to Transplant Rejection......Page 802
References......Page 803
Definitions, Clinical Presentation, and Diagnosis......Page 805
Molecular Genetics of HCM......Page 807
Screening and Treatment for HCM......Page 811
References......Page 814
Primary Abnormalities in Cardiac Rhythm: Ventricular Tachyarrhythmias......Page 818
Complex Forms of Lqts......Page 825
Familial Vt/cpvt......Page 830
Primary Conduction Abnormalities......Page 831
References......Page 834
Genetics of Coagulation......Page 844
Human Hemostatic Variability......Page 845
Genotype–phenotype Influences......Page 846
Gene-environment Influences on Hemostasis......Page 847
Circulating Cellular and Protein Influences on Hemostasis and Thrombosis......Page 848
Race-related Influences on Hemostasis and Thrombosis......Page 849
Association Studies in Thrombosis......Page 851
A Personalized Approach to Hemostasis and Thrombosis......Page 852
Patient Screening: A Traditional Paradigm......Page 853
Patient Screening: A Comprehensive and Population-based Approach......Page 856
Emerging Platform for Hemostasis and Thrombosis Research......Page 857
References......Page 858
Clinical Manifestations of PAD......Page 862
Therapeutic Strategies for PAD......Page 863
Gene Polymorphisms Contributing to Atherosclerosis and PAD......Page 864
Identification of Novel Gene Polymorphisms Involved in PAD......Page 865
Future Potential Use of Genomic Methodologies in PAD......Page 866
References......Page 867
CHD Gene Discovery by Conventional Genetics......Page 870
Genomic Strategies for CHD Gene Discovery......Page 875
Cytogenetic and Molecular Genetic testing......Page 876
Medical Evaluation and Counseling Recommendations......Page 877
Conclusion......Page 878
References......Page 879
Recommended Resources......Page 882
Introduction......Page 883
Why Perioperative Insults are not Equivalent to Chronic Ambulatory Disease......Page 884
Perioperative Venous and Arterial Thrombosis......Page 885
Perioperative Stroke and Neurocognitive Dysfunction......Page 887
Dynamic Genomic Markers of Perioperative Outcomes......Page 888
References......Page 889
Section 9 Oncology Genomic Medicine......Page 896
Chromosomal Aberrations and Cancer......Page 897
Inherited Predisposition......Page 898
Cellular Progression Toward Cancer Through Somatic Changes......Page 899
Comprehensive Sequencing of the Kinome......Page 900
Multiple Molecular Mechanisms for Oncogene Activation......Page 901
Cancer Genomic Databases Expedite Progress......Page 902
Future Directions......Page 903
References......Page 904
Introduction......Page 907
Immune Cells of the Tumor Microenvironment......Page 908
Examples of Tissue or Gene Microarrays used to Study Tumors......Page 911
Genomic Studies of Immune Stimulation within the Microenvironment......Page 912
Genomic Analysis of Tumor Microenvironment in Immunotherapy Studies......Page 913
Conclusion......Page 914
References......Page 915
Introduction......Page 919
Diffuse Large B-cell Lymphoma......Page 922
Hodgkin Lymphoma......Page 924
Follicular Lymphoma......Page 925
Mantle Cell Lymphoma......Page 927
Miscellaneous Lymphomas......Page 928
References......Page 929
Introduction......Page 933
Genomics in Leukemias – Insights into Leukemia Biology......Page 935
Genomics in Leukemias – Evaluation of Drug Effects......Page 936
Genomics in Leukemias – Clinical Outcome Prediction......Page 938
Conclusions......Page 940
References......Page 941
Recommended Resources......Page 944
Introduction......Page 945
Early Diagnosis/screening of Lung Cancer......Page 946
Classification and Prognosis......Page 948
Pathogenesis and Treatment of Lung Cancer......Page 951
Conclusion......Page 954
References......Page 955
Recommended Resource......Page 957
The Promise......Page 958
Molecular Bases......Page 960
Molecular Markers......Page 961
Netherlands Cancer Institute Study......Page 962
Nsabp Study......Page 964
The Reality of Clinical Genomics......Page 965
References......Page 966
Introduction......Page 968
Genomic Model of CRC......Page 969
Predisposition for CRC......Page 971
Risk Assessment, Evaluation, and Genetic Testing......Page 976
Prognosis and Treatment......Page 978
Pharmacogenetics/genomics of Chemoprevention and Chemotherapy......Page 979
Conclusion......Page 981
References......Page 982
Genetic Predisposition and Alterations in Prostate Cancer......Page 987
Prostate Cancer Detection......Page 990
Genomic Changes Associated with Prostate Cancer Behavior......Page 993
Genomic Changes Associated with Hormone-Refractory Prostate Cancer......Page 995
Future Prospects of Genomics in Prostate Cancer Care......Page 996
References......Page 997
Inherited Ovarian Cancer Syndromes......Page 1002
Fanconi/anemia Pathway......Page 1003
Somatic Mutations in Ovarian Cancer......Page 1004
Oncogenes and Growth Factors......Page 1005
Ovarian Cancer Metastases......Page 1006
Angiogenesis......Page 1007
References......Page 1008
Introduction......Page 1010
Screening......Page 1011
Diagnosis......Page 1012
Prognosis......Page 1015
Conclusion......Page 1016
References......Page 1017
Introduction......Page 1020
The Multiple Endocrine Neoplasia Syndromes......Page 1021
Acknowledgements......Page 1030
References......Page 1031
Recommended Resources......Page 1033
Head and Neck Squamous Cell Carcinoma......Page 1034
Conclusion......Page 1041
References......Page 1042
Recommended Resources......Page 1044
Introduction......Page 1045
Predisposition......Page 1046
Diagnosis and Prognosis......Page 1047
Pharmacogenomics......Page 1050
Novel and Emerging Therapeutics......Page 1051
Conclusions......Page 1052
References......Page 1053
Diagnosis......Page 1056
Genetics of Melanoma......Page 1057
Novel and Emerging Therapeutics......Page 1058
References......Page 1062
Introduction......Page 1066
Tools to Investigate the Mechanisms of Metastasis......Page 1068
Assessement of Prognosis and New Treatments for Metastasis: the Role of New Technologies......Page 1075
Conclusion......Page 1076
References......Page 1077
Recommended Resources......Page 1078
The Ideal Target......Page 1079
The First Diagnostic-therapeutic Combination in Cancer Therapy: Hormonal Therapy for Breast Cancer......Page 1081
Her-2 Positive Breast Cancer and Trastuzumab (Herceptin®)......Page 1083
Other Targeted Anticancer Therapies Using Antibodies......Page 1084
Selected Targeted Anticancer Therapies Using Small Molecules......Page 1088
Pharmacogenomics......Page 1091
References......Page 1092
Section 10 Inflammatory Disease Genomic Medicine......Page 1098
Importance of Environmental Exposures in Human Health......Page 1099
Comparative Environmental Genomics......Page 1101
Exposure Assessment in the Gene-environment Paradigm......Page 1102
References......Page 1104
Introduction......Page 1106
Predisposition......Page 1107
Pharmacogenomics......Page 1113
References......Page 1115
Genomics in MS......Page 1121
Transcriptomics in MS......Page 1123
Immunomics in MS......Page 1124
Proteomics in MS......Page 1125
References......Page 1126
Introduction......Page 1129
Predisposition (Genetic and Non-genetic)......Page 1130
Screening......Page 1132
Diagnosis......Page 1133
Prognosis......Page 1134
Monitoring......Page 1136
Novel and Emerging Therapeutics......Page 1137
Conclusions......Page 1138
References......Page 1139
Techniques for Detection, Quantification, and Profiling of mRNA Expression in the Kidney......Page 1145
mRNA Expression Profiles of Glomerular Disorders......Page 1148
Genome Variations in Glomerular Disorders......Page 1149
Genomic Medicine for Glomerular Disorders......Page 1151
References......Page 1153
Characteristics of SPA......Page 1156
Role of Bowel Inflammation......Page 1159
Histopathology of Synovitis in SPA......Page 1161
Gut and Synovium Transcriptomes......Page 1163
Novel and Emerging Therapeutics and Biomarkers......Page 1164
Conclusions......Page 1166
References......Page 1167
Asthma: Basic Pathobiology......Page 1173
Genome-wide Linkage Analyses of Asthma and its Intermediate Phenotypes......Page 1174
Candidate-gene Association Studies of Asthma......Page 1176
Screening......Page 1177
Pharmacogenetics......Page 1180
Monitoring......Page 1181
References......Page 1182
Recommended Resources......Page 1186
Predisposition......Page 1187
Pathophysiology......Page 1188
Cellular and Molecular Mechanisms......Page 1190
Diagnosis and Screening......Page 1193
Management......Page 1194
Conclusions......Page 1196
References......Page 1197
Introduction......Page 1199
Genetic Determinants of Sarcoidosis......Page 1200
Surfactant Proteins and Dpld......Page 1203
Genetic Determinants of Fip......Page 1204
Conclusion......Page 1206
References......Page 1207
Introduction......Page 1211
Clinical and Physiological Aspects of Pud......Page 1212
Pathophysiology of Ulcer Formation......Page 1213
The Helicobacter Genome......Page 1214
Human Polymorphism and Pud......Page 1219
Genomics in the Management of Disease......Page 1220
Conclusions......Page 1221
References......Page 1222
Recommended Resources......Page 1226
Liver Structure......Page 1227
Diagnosis of Cirrhosis......Page 1229
Treatment of Cirrhosis......Page 1230
Genetics of Cirrhosis......Page 1231
The Liver Proteome......Page 1232
Development of Liver Fibrosis......Page 1233
Transcriptome Analysis of Liver Disease......Page 1235
Proteomic Studies of Liver Disease......Page 1237
Proteomics in Other Liver Disease......Page 1239
References......Page 1240
Predisposition......Page 1244
Screening......Page 1247
Monitoring and Genomic Factors......Page 1248
Therapeutic Strategies......Page 1251
Novel and Emerging Therapeutics......Page 1253
References......Page 1254
Section 11 Metabolic Disease Genomic Medicine......Page 1258
Obesity: Causes and Genetic Predisposition......Page 1259
Search of Genes Involved in Obesity......Page 1261
Diagnosis and Characterization of Genes Associated with Obesity......Page 1264
Screening and Diagnosis......Page 1268
Prognosis and Gene Based-treatments......Page 1269
Novel and Emerging Therapeutics Nutrigenomics, Pharmacogenomics and Gene Therapy......Page 1271
Acknowledgements......Page 1272
References......Page 1273
Introduction......Page 1276
GWAS in Type 2 Diabetes......Page 1277
Future Research in Type 2 Diabetes Genetics......Page 1279
GWAS in Type 1 Diabetes......Page 1280
References......Page 1281
Diagnosis: Definition of the MetS Phenotype......Page 1283
Genetics of MetS......Page 1285
References......Page 1289
Recommended Resources......Page 1291
Introduction......Page 1293
Methodological Issues......Page 1294
Gene–Nutrient Interactions......Page 1295
Conclusions......Page 1303
References......Page 1304
Introduction......Page 1311
Incidence of Dementia......Page 1312
Primary Dementias......Page 1313
Future Prospects for Genomic Medicine in the Dementias......Page 1318
References......Page 1319
Recommended Resources......Page 1321
Section 12 Neuropsychiatric Disease Genomic Medicine......Page 1310
Clinical Characteristics of PD......Page 1322
Genetics of PD......Page 1324
Genetics of Sporadic PD......Page 1327
References......Page 1330
Recommended Resources......Page 1331
Mendelian Epilepsies......Page 1332
Common Epilepsies......Page 1337
Future Program of Work......Page 1340
References......Page 1341
Introduction......Page 1345
Cornea......Page 1346
Trabecular Meshwork......Page 1348
Retina......Page 1349
References......Page 1350
Motor Neuron Disease......Page 1354
Disorders of the Neuromuscular Junction......Page 1355
Predisposition......Page 1357
Screening......Page 1362
Prognosis......Page 1363
Monitoring......Page 1364
Current, Novel, and Emerging Therapies......Page 1365
Advances in Genomics and Proteomics......Page 1366
References......Page 1368
Recommended Resources......Page 1370
Great Prospect, But are We There Yet?......Page 1371
How Complex Can it Be?......Page 1372
Converging Methods......Page 1373
Personalized Medicine......Page 1374
Conclusion......Page 1375
References......Page 1376
Diagnosis, Prevalence and Course of Depression......Page 1378
Pathophysiological Mechanisms......Page 1379
Pharmacogenomics of Antidepressants......Page 1382
Current Concepts......Page 1383
References......Page 1385
Diagnosis......Page 1388
Predisposition......Page 1389
Pharmacogenetics......Page 1393
The Role of New Technologies in Elucidating the Genetics of BPD......Page 1394
References......Page 1397
Section 13 Infectious Disease Genomic Medicine......Page 1402
Introduction......Page 1403
Genetic Susceptibility to Pathogens......Page 1404
Exploring the Host Response Through Expression Profiling......Page 1406
References......Page 1409
Recommended Resources......Page 1412
Context of HIV and AIDS......Page 1413
Diagnosis......Page 1417
Prognosis......Page 1418
Pharmacogenomics......Page 1420
Novel and Emerging Therapeutics......Page 1422
References......Page 1423
Introduction......Page 1429
Viral Genomics and the Antiviral Drug Revolution Era......Page 1430
Conclusion......Page 1433
References......Page 1434
Genomics and the Study of Bacterial Infections......Page 1436
Host Genomics and Gram-positive, Gram-negative and Mycobacterial Infections......Page 1440
References......Page 1446
Introduction......Page 1451
Genetic Polymorphisms Associated with Sepsis......Page 1452
Molecular Signatures and Sepsis......Page 1457
Conclusion......Page 1460
References......Page 1461
Virology of Hepatitis Viruses......Page 1464
Acquisition and Predisposition to Viral Hepatitis......Page 1466
Screening and Diagnosis of Viral Hepatitis......Page 1467
Pathogenesis of Viral Hepatitis......Page 1469
Therapeutics and Pharmacogenomics......Page 1473
References......Page 1475
A......Page 1480
B......Page 1481
C......Page 1482
E......Page 1484
G......Page 1485
H......Page 1486
I......Page 1487
M......Page 1488
P......Page 1490
Q......Page 1491
S......Page 1492
V......Page 1494
Y......Page 1495
A......Page 1496
B......Page 1502
C......Page 1505
D......Page 1514
E......Page 1517
F......Page 1520
G......Page 1522
H......Page 1526
I......Page 1531
K......Page 1534
L......Page 1535
M......Page 1537
N......Page 1543
O......Page 1545
P......Page 1546
R......Page 1554
S......Page 1556
T......Page 1561
U......Page 1564
V......Page 1565
W......Page 1566
Z......Page 1567