Susceptibility to Infectious Diseases: The Importance of Host Genetics (Advances in Molecular and Cellular Microbiology)

Cover......Page 1
Half-title......Page 3
Title......Page 6
Copyright......Page 7
Contents......Page 8
Contributors......Page 10
CHAPTER 1 Introduction......Page 18
REFERENCES......Page 22
1. INTRODUCTION......Page 24
2. LINKAGE ANALYSIS......Page 26
2.1 Model-Based Methods......Page 28
2.2 Model-Free Methods......Page 30
2.3 Conclusions......Page 33
3. ASSOCIATION STUDIES......Page 34
5. GENOME SCREENS......Page 38
6. THE MAJOR HISTOCOMPATIBILITY COMPLEX......Page 41
6.1 The NRAMP1 Gene......Page 43
6.2 The VDR Gene......Page 45
6.3 The MBL Gene......Page 46
7. DISCUSSION......Page 47
8. CONCLUSION......Page 48
REFERENCES......Page 50
1. INTRODUCTION......Page 62
2. INFECTIONS AND TREATMENT......Page 64
4. GENETIC BASIS......Page 70
4.1 Immunological Recognition Molecules......Page 72
5. ANTIBODY DEFICIENCIES......Page 73
6.1 T-B+ SCID......Page 74
6.2 T-B+ SCID......Page 75
6.4 Major Histocompatibility Complex Deficiencies......Page 76
6.5 Hyper IgM Syndrome......Page 77
7. OTHER WELL-DEFINED PIDs......Page 78
8.1 Chronic Granulomatous Disease......Page 79
8.2 Leukocyte Adhesion Defects......Page 80
8.4 Glucose 6-Phosphate Dehydrogenase Deficiency......Page 81
10. COMPLEMENT DEFECTS......Page 82
11. IMMUNODEFICIENCY MUTATION DATABASES (IDBASES)......Page 84
REFERENCES......Page 89
1. INTRODUCTION: THE NATURAL HISTORY OF INFECTIOUS DISEASES......Page 94
3. THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX......Page 95
4. LINKAGE DISEQUILIBRIUM AND HLA HAPLOTYPES......Page 101
5. THE DESIGN OF STUDIES OF HLA AND DISEASE OUTCOME......Page 102
6. STATISTICAL ISSUES IN MHC ASSOCIATIONS......Page 103
8. DISEASE ASSOCIATION STUDIES......Page 105
9. MECHANISM OF MHC ASSOCIATIONS......Page 111
10. HOST–PARASITE INTERACTIONS......Page 117
11. EVOLUTIONARY ORIGINS OF THE HLA COMPLEX......Page 118
12.1 Prognostic Information......Page 119
13. RESPONSES TO THERAPY AND VACCINATION......Page 120
15. CONCLUSIONS......Page 122
REFERENCES......Page 123
1. INTRODUCTION......Page 134
2. WHAT IS CF?......Page 135
3. APICAL MEMBRANE LOCATION OF CFTR......Page 137
4. THE ROLE OF CFTR IN EPITHELIAL TRANSPORT PROCESSES......Page 138
5.1 Effects on Airway Surface Liquid (ASL)......Page 139
5.2 Protein Processing, Bacterial Adherence, and CF......Page 144
5.3 Other Regulatory Functions of CFTR and Bacterial Infection......Page 146
7. HETEROZYGOTE ADVANTAGE AGAINST INFECTIOUS DISEASE......Page 147
8. SUMMARY......Page 149
REFERENCES......Page 150
1. INTRODUCTION......Page 156
2. THE CONTRIBUTION OF GENETIC TRAITS TO RESISTANCE TO MALARIA......Page 158
3.1 Association Studies......Page 159
3.3 Linkage Studies......Page 160
4.1 Haemoglobinopathies......Page 162
4.1.2.1 Population Genetics of the Thalassaemias......Page 164
4.1.2.2 Epidemiological Studies......Page 166
4.2 Red Cell Enzymes......Page 167
4.3.1 Reduced Invasion and Growth......Page 168
4.3.2 Cytoadherence of P. falciparum-Infected Variant Red Blood Cells......Page 169
4.3.3 Phagocytosis......Page 171
4.3.4 Immune-Mediated Mechanisms......Page 172
4.4.1 Duffy Blood Group System......Page 174
4.4.2 Other Red Blood Cell Surface Antigens......Page 176
4.5.1 Southeast Asian Ovalocytosis......Page 177
4.5.2 Other Red Cell Cytoskeletal Proteins......Page 178
4.6.1 HLA Class I and Class II......Page 179
4.6.2 Tumour Necrosis Factor and Other Cytokines......Page 180
4.6.3 Nitric Oxide Synthase......Page 182
4.7 Host Receptors for Infected Erythrocytes on Endothelium and Uninfected Erythrocytes......Page 183
5. NEGATIVE ASSOCIATION STUDIES......Page 185
6. CONCLUSION......Page 186
REFERENCES......Page 187
CHAPTER 7 Polymorphic chemokine receptor and ligand genes in HIV infection......Page 202
1. CLASSIFICATION, EVOLUTION, AND FUNCTION OF CHEMOKINE RECEPTORS AND THEIR LIGANDS......Page 204
2. CHEMOKINE SYSTEM AND HIV-1 INFECTION......Page 207
3. CHEMOKINE RECEPTOR AND LIGAND POLYMORPHISMS: REGIONAL AND GLOBAL DISTRIBUTION AND DELINEATION OF GENOTYPE–PHENOTYPE RELATIONSHIPS......Page 208
4. POLYMORPHISMS OF CHEMOKINE RECEPTOR AND LIGAND GENES IN RELATION TO HIV-1 INFECTION, HOST–VIRUS EQUILIBRATION, AND DISEASE PROGRESSION......Page 212
5. APPLICATIONS OF IMMUNOGENETIC FINDINGS......Page 216
6. SUMMARY......Page 217
REFERENCES......Page 218
1. INTRODUCTION......Page 238
2.1 Discovery of the Ity/Lsh/Bcg Locus......Page 239
2.2 Positional Cloning of the Mouse Nramp1 Gene......Page 241
2.3 Expression of Nramp1 in Professional Phagocytes......Page 242
2.4 Divalent Cation Transport by Nramp Proteins......Page 243
2.5 Nramp1 Transport at the Phagosomal Membrane......Page 246
2.6 Consequences of Nramp1-Dependent Divalent Cation Transport on Microbial Virulence......Page 247
2.7 Conclusions and Perspectives from Studies in Mice......Page 249
3.1 Livestock Species......Page 251
3.2 Human NRAMP1......Page 252
3.3 Genetic Studies Employing NRAMP1 as Candidate Gene......Page 254
4. NRAMP1 AND TUBERCULOSIS......Page 255
5. NRAMP1 AND LEPROSY......Page 258
6. NRAMP1 AND INFECTIONS OTHER THAN TUBERCULOSIS AND LEPROSY......Page 259
7. NRAMP1 AND AUTOIMMUNE DISORDERS......Page 260
8. CONCLUSIONS FROM STUDIES IN HUMAN POPULATIONS......Page 261
REFERENCES......Page 262
1. INTRODUCTION......Page 276
2.1.1 Complete IFNgammaR1 Deficiency......Page 278
2.1.2 Partial IFNgammaR1 Deficiency......Page 279
2.3 STAT1 Mutations......Page 281
2.5 IL-12RB1 Mutations......Page 282
3.1 IFNgamma o/o Mice and IFNgamma R o/o Mice......Page 283
3.2 IL12p40 o/o, IL12p35 o/o, and IL12p35 o/o p40 o/o Mice......Page 284
3.4 TNFgamma, TNFR1 o/o Mice: IFNγ-Inducible Genes......Page 286
4. IRF-1 AND NOS2: OTHER IFNγ-INDUCIBLE GENES......Page 287
5. CONCLUSIONS......Page 288
REFERENCES......Page 289
1. INNATE IMMUNITY......Page 296
3. MANNOSE-BINDING LECTIN......Page 297
4. MBL DEFICIENCY AND GENETICS......Page 300
6. MBL DISEASE ASSOCIATIONS......Page 304
6.1 Meningococcal Disease......Page 307
6.2 HIV Infection......Page 311
6.3 Neutropenia......Page 312
7. THE ROLE OF MBL DEFICIENCY......Page 314
8. CLINICAL PRESENTATION OF MBL DEFICIENCY......Page 315
REFERENCES......Page 316
1. INTRODUCTION......Page 326
2. HYPOTHESES......Page 327
3.1 Binding of Microorganisms to Host Cells......Page 329
3.3 Binding of Synthetic Blood Group Antigens......Page 332
4.1 Frequency of Colonisation......Page 333
4.3 Secretor Status and Density of Colonisation......Page 335
5. BINDING OF BACTERIA TO BLOOD GROUP ANTIGENS: ASSESSMENT OF EXPERIMENTAL STUDIES IN RELATION TO EPIDEMIOLOGY......Page 336
5.1 Environmental Factors Affect Expression of Blood Group Antigens and Bacterial Binding......Page 337
6.1.1 Protection......Page 338
6.1.2 Tolerance......Page 339
7.1 H. pylori and Peptic Ulcers......Page 340
7.3 H. pylori and Ischaemic Heart Disease (IHD)......Page 341
REFERENCES......Page 343
CHAPTER 12 Genetics of human susceptibility to infection and hepatic disease caused by schistosomes......Page 354
1.1 Evidence that a Major Gene is Involved in the Control of Infection......Page 356
1.2 Localisation of SM1 on Chromosome 5q31-q33......Page 359
1.3 Search for Additional Loci Controlling the Levels of S. mansoni Infection......Page 360
2.1 The Egg Granuloma......Page 361
2.2 Susceptibility to Periportal Fibrosis Caused by Schistosoma mansoni in a Sudanese Population......Page 362
2.3 Severe Hepatic Fibrosis is Controlled by SM2 Located in the 6q22-q23 Region......Page 364
3. HOW DOES (DO) THE GENE(S) IN 5q31-q33 CONTROL S. MANSONI INFECTION?......Page 366
4. ROLE OF INTERFERON-gamma AND TNF-alpha IN SUSCEPTIBILITY TO HEPATIC FIBROSIS CAUSED BY S. MANSONI......Page 367
5. CONCLUSION......Page 371
REFERENCES......Page 372
1. WHAT ARE PRION DISEASES?......Page 378
2. WHAT IS A PRION?......Page 379
3. GENETICS OF PRION DISEASE......Page 380
3.1 Experimental Genetics in Prion Disease......Page 381
3.2 The Prion Protein Gene (PRNP)......Page 383
3.4 Codon 129 Polymorphism......Page 384
3.5 Other Gene Regions......Page 387
4.2 Diagnosis of CJD – Clinical......Page 388
4.3 Diagnosis of TSE – Protein Laboratory......Page 389
4.4 Diagnosis of TSE – Genetics Laboratory......Page 392
5.1 Genetic Susceptibility to Sporadic CJD (sCJD)......Page 393
5.2 Genetic Susceptibility to Familial CJD (fCJD)......Page 395
5.2.1 CJD Phenotype Mutations......Page 396
5.2.3 Fatal Familial Insomnia (FFI) Phenotype Mutation......Page 397
5.3.1 Iatrogenic CJD (iCJD)......Page 398
5.3.2 Kuru......Page 401
5.3.3 Variant CJD......Page 402
REFERENCES......Page 403
Index......Page 410