| Publications by Biophoenix' Principals |
| DNA Diagnostics II | |
|---|---|
 | |
| Publisher: | PJB Publications Ltd |
| Year of publication: | 1993 |
| Type of publication: | Management report |
| Publisher's reference (if any): | CBS 396WC |
| Author(s): | Sreten Bogdanovic |
| Approximate page count: | 250 |
| Price when published: | £350 |
Remarks:
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DNA DIAGNOSTICS
(Second Edition)
A report for
Clinica World Medical Device and Diagnostic News
(c) April 1993 by PJB Publications
CONTENTS
PAGE
CONTENTS i
LIST OF TABLES AND FIGURES vii
EXECUTIVE SUMMARY 1
CHAPTER 1: INTRODUCTION AND BACKGROUND
1.1 Scope of this report 6
1.2 Summary of the main applications of DNA analysis 9
1.3 Overview of DNA diagnostics end-users 10
1.4 Nucleic acid structure and function 11
1.4.1 Introduction 11
1.4.2 The structure of proteins 12
1.4.3 The structure of nucleic acids 13
1.4.4 RNA 15
1.4.5 DNA 15
1.4.6 The genetic code 15
1.4.7 Function of nucleic acids 17
1.4.7.1 Introduction 17
1.4.7.2 DNA replication 18
1.4.7.3 RNA and transcription 19
1.4.7.4 Processing of RNA 20
1.4.7.4.1 Capping and tailing 20
1.4.7.4.2 Splicing 21
1.4.7.4.3 Function of introns 22
1.4.7.5 Protein synthesis 22
1.4.7.6 A second genetic code? 23
1.5 Classical genetics 24
1.5.1 Genes 24
1.5.2 Linkage 26
1.5.3 Recombination 26
1.5.4 Genetic mapping 27
1.5.5 Linkage phase 27
1.5.6 Sex linkage 28
1.5.7 Number of genes in man 28
1.5.8 C-value paradox 29
1.6 Repetitive DNA 29
1.7 Chromosomes and cytogenetics 29
1.7.1 Nomenclature 29
1.7.2 Chromosomal aberrations 30
1.7.3 Karotypes 31
1.8 Genetic imprinting 31
1.9 Restriction enzymes 33
1.10 Other means of site-directed DNA cleavage 34
1.11 Methylation of DNA 34
1.12 Cloning vectors 35
1.12 DNA probes 36
1.12.1 Description 36
1.12.2 Probe development 37
1.12.3 Probes of clonal origin 38
1.12.4 An example: the development of
DNA probes for haemoglobin disorders 39
1.12.5 Development of DNA probes for genetic
disorders of unknown aetiology 40
1.12.6 Development of DNA probes for
infectious diseases 42
1.13 DNA Amplification 42
1.13.1 Overview 42
1.13.2 The polymerase chain reaction (PCR) 43
1.13.2.1 Introduction 43
1.13.2.2 Power of PCR 43
1.13.2.3 Performing the PCR 44
1.13.2.4 Detecting the amplified PCR products 45
1.13.2.5 Drawbacks of PCR 46
1.13.2.6 Wider applications of PCR 47
1.13.2.7 Current position of PCR 49
1.13.2.8 PCR products 51
1.13.3 Ligase chain reaction 53
1.13.4 Q-beta replicase amplification system 55
1.13.5 Other DNA amplification systems 56
1.14 DNA preparation 58
1.14.1 Introduction 58
1.14.2 Acceptable sample materials 58
1.14.3 Solvent or organic extraction 58
1.14.4 Disposable columns 59
1.14.5 In situ hybridisation 60
1.14.6 Extraction of mRNA 60
1.15 DNA test formats 60
1.15.1 Introduction 60
1.15.2 Heterogeneous assays 61
1.15.2.1 Dot and slot blotting 61
1.15.2.2 Southern blotting 61
1.15.2.3 In Situ hybridisation 62
1.15.2.4 Affinity capture techniques 62
1.15.2.5 Reversed hybridisation 63
1.15.3 Homogeneous assays 63
1.15.4 Assays adaptable to solid or liquid phases 64
1.15.4.1 Strand displacement 64
1.15.4.2 Sandwich hybridisation 64
1.16 Nucleic acid labelling systems 65
1.16.1 Incorporation of labels into DNA and RNA 65
1.16.2 Radioisotopes 66
1.16.3 Nonisotopic labels 67
1.16.3.1 Introduction 67
1.16.3.2 Biotin tagging 67
1.16.3.3 Labels for use with biotin 68
1.16.3.4 Incorporation of biotin tags into DNA 68
1.16.3.5 Other DNA probe tags 69
1.16.3.6 Direct labelling of DNA 69
1.16.4 DNA sensors 70
CHAPTER 2: MONOGENIC DISORDERS
2.1 Introduction 71
2.2 Types of genetic disease 71
2.3 Types of mutation seen in genetic disease 72
2.4 DNA testing in genetic disease 75
2.4.1 Introduction 75
2.4.2 The importance of genetic linkage 75
2.4.3 The family study 76
2.4.4 The role of restriction enzymes 76
2.4.5 Gel electrophoresis, blotting, and probing 77
2.4.6 Restriction fragment length polymorphisms (RFLPs) 77
2.4.7 DNA diagnosis of genetic diseases by gene tracking 78
2.4.8 Assays for new mutations 80
2.4.9 Practical DNA testing in genetic disease 82
2.4.9.1 Assay procedures 82
2.4.9.2 Sources of sample material 83
2.4.9.3 Pre-implantation diagnosis 84
2.5 Detecting genetic disease in utero 84
2.5.1 Introduction 84
2.5.2 Analysis of amniotic fluid 85
2.5.3 Enzyme assays in cultured amniocytes 85
2.5.4 Chorionic villus sampling (CVS) 86
2.5.5 Analysis of foetal blood and other tissues 86
2.5.6 Ultrasound 87
2.6 Survey of important inherited diseases 87
2.6.1 Alpha-1-antitrypsin deficiency 87
2.7.2 Congenital adrenal hyperplasia 87
2.7.3 Cystic fibrosis 88
2.7.4 Duchenne muscular dystrophy 92
2.7.5 Haemophilias A and B 93
2.7.6 Huntington's disease 94
2.7.7 Neurofibromatosis 95
2.7.8 Myotonic dystrophy 96
2.7.9 Phenylketonuria 98
2.7.10 Polycystic kidney disease 98
2.7.11 Spinal muscular atrophy 99
2.7.12 The haemoglobinopathies 100
2.7.13 Fragile X-linked mental retardation 100
2.8 Chromosomal disorders 104
2.8.1 DNA Methods in cytogenetics 104
2.8.2 Spectrum of chromosomal disorders 104
2.8.3 DNA products and services 105
2.9 Economics of DNA testing 106
2.10 Expected workload in a DNA reference laboratory 106
CHAPTER 3: POLYGENIC DISORDERS AND RELATED APPLICATIONS
3.1 Introduction 109
3.2 Alzheimer's disease 110
3.3 Coronary artery disease 111
3.4 Obesity and diabetes 112
3.5 Immunological diseases 115
3.6 Psychiatric disorders 115
3.6.1 Schizophrenia 115
3.6.2 Manic-depressive psychosis 117
3.6.3 Alcoholism 117
3.7 The Human Genome Project 118
3.7.1 Introduction 118
3.7.2 Organisation 118
3.7.3 Strategy 119
3.7.4 Gene mapping technology 119
3.7.5 Benefits from the Genome Project 121
3.7.5.1 The detection of monogenic disorders 121
3.7.5.2 The management of polygenic disorders 121
3.7.5.3 Pharmaceutical development 122
3.7.5.4 Use of a genetic map 123
3.7.6 Some preliminary insights
from human gene mapping 124
3.7.7 Commercial instrumentation 128
3.8 DNA fingerprinting 128
3.8.1 Introduction 128
3.8.2 Applications 128
3.8.3 Satellite and minisatellite DNA 129
3.8.4 DNA fingerprinting/DNA profiling 129
3.8.5 `Digital' DNA fingerprinting 131
3.8.6 Commercial development 132
3.8.7 DNA profiling in the courts 134
3.8.8 Regulatory and quality control issues 135
3.8.9 Prospects in DNA profiling 136
3.9 Pre-employment screening and DNA diagnostics 137
3.10 Plant and animal DNA diagnostics 137
3.11 Security-related applications
of DNA diagnostics 137
CHAPTER 4: CANCER
4.1 Introduction 139
4.2 Incidence of cancer 139
4.3 The nature of cancer 140
4.3.1 Environmental and lifestyle factors 140
4.3.2 Control of growth rate 141
4.3.3 Tumour initiation 141
4.3.4 Tumour promotion 141
4.3.5 Tumour progression 142
4.3.6 Characteristics of malignant cells 142
4.3.7 Diagnosis, prognosis, and monitoring 143
4.3.7.1 Introduction 143
4.3.7.2 Tumour staging 143
4.3.7.3 Tumour grading 143
4.3.7.4 Tumour monitoring 144
4.4 Molecular events in tumour formation 145
4.4.1 Somatic and germ-line mutations 145
4.4.2 Viruses and cancer 145
4.4.3 Oncogenes 146
4.4.3.1 Nomenclature of oncoproteins 146
4.4.3.2 Nature of oncogenes 146
4.4.3.3 Mode of action of oncogenes 149
4.4.4 Inheritance of cancer 152
4.4.4.1 Introduction 152
4.4.4.2 Retinoblastoma and anti-oncogenes 154
4.4.4.3 Wilm's tumour 155
4.4.4.4 Other deletion-associated malignancies 155
4.4.5 The p53 gene 157
4.4.6 Molecular biology of tumour
progression in colon cancer 158
4.4.7 Conclusions 160
4.5 Use of DNA Probes in cancer diagnostics 161
4.5.1 Overview 161
4.5.1 Oncogene assays 161
4.5.2 bcr analysis 163
4.5.3 B/T cell DNA analysis 164
4.5.4 Other haematogenous malignancies 165
4.5.5 DNA tests in cervical cancer 166
4.5.5.1 Potential role of DNA tests 166
4.5.5.2 DNA assays in HPV typing 167
4.5.5.3 Some caveats 168
4.5.5.4 Availability of HPV DNA tests 168
4.5.6 Helicobacter pylori and stomach cancer 168
4.5.7 Immunoassay tumour markers vs DNA tests 169
4.5.8 Commercial availability
of DNA diagnostic products 171
CHAPTER 5: INFECTIOUS DISEASE
5.1 Introduction 172
5.2 Methodology 172
5.3 Kit availability and commercialisation 173
5.4 Survey of specific bacterial pathogens 174
5.4.1 Bacteroides species 174
5.4.2 Campylobacter 177
5.4.3 Chlamydia 177
5.4.4 Clostridia 178
5.4.5 Escherichia coli 178
5.4.6 Gonorrhoea 178
5.4.7 Hemophilus influenzae 179
5.4.8 Legionella 179
5.4.9 Leptospirosis 180
5.4.10 Listeria 180
5.4.11 Lyme disease 180
5.4.12 Mycobacteria 181
5.4.13 Mycoplasmas 181
5.4.14 Neisseria meningitidis 181
5.4.15 Salmonellae 182
5.4.16 Shigellae 182
5.4.17 Staphylococcus aureus 182
5.4.18 Streptococcus 183
5.4.19 Treponema pallidum 183
5.5 Survey of specific viral pathogens 184
5.5.1 Adenovirus 184
5.5.2 Cytomegalovirus 184
5.5.3 Epstein Barr virus 185
5.5.4 Herpes simplex 185
5.5.5 Human immunodeficiency virus 186
5.5.6 Hepatitis 187
5.5.7 Parainfluenza virus 187
5.5.8 Respiratory syncytial virus 188
5.5.9 Rotavirus 188
5.5.10 Rubella 188
5.5.11 Varicella-zoster virus 189
5.6 Survey of specific parasitic pathogens 189
5.6.1 Entamoeba histolytica 189
5.6.2 Leishmaniasis 189
5.6.3 Plasmodium 190
5.6.4 Pneumocystis carinii 190
5.6.5 Tapeworms (Taeniids) 190
5.6.6 Trichomonas vaginalis 190
5.7 Survey of specific fungal pathogens 191
5.7.1 Histoplasma capsulatum 191
5.7.2 Aspergillus species 191
5.7.3 Yeast pathogens 191
5.7.4 Coccidioides immitis 191
5.7.5 Cryptococcus neoformans 192
5.8 Other infectious agents: the prion diseases 192
5.8.1 Introduction 192
5.8.2 Bovine spongiform encephalopathy 192
5.8.3 Human spongiform encephalopathies 193
5.8.4 DNA diagnosis of prion diseases 193
5.9 Immunoassays and DNA probes 195
CHAPTER 6: PRESENT STATUS OF THE DNA DIAGNOSTIC MARKET
6.1 Introduction 197
6.2 Market forecasts 197
6.2.1 Monogenic disorders 197
6.2.2 Chromosomal disorders 199
6.2.3 Polygenic disorders 199
6.2.4 DNA profiling 200
6.2.5 Cancer 201
6.2.6 Infectious diseases 202
6.2.7 Instrumentation 205
6.3 Company profiles 219
6.3.1 Introduction 219
6.3.2 Abbott Laboratories 219
6.3.3 Applied Biosystems Incorporated 220
6.3.4 Baxter Healthcare 221
6.3.5 Becton Dickinson and Company 222
6.3.6 Boehringer Mannheim GmbH 223
6.3.7 Cetus Corporation 225
6.3.8 Chiron Corporation 226
6.3.9 Collaborative Research Incorporated 227
6.3.10 Digene Diagnostics 228
6.3.11 Enzo Biochem Incorporated 229
6.3.12 Gen-Probe Corporation 231
6.3.13 Genzyme/Integrated Genetics 232
6.3.14 ImClone Systems Incorporated 233
6.3.15 Oncogene Science 234
6.3.16 Oncor Incorporated 235
6.3.17 Orgenics Limited 235
6.3.18 Orion Corporation Limited 236
6.3.19 Roche Diagnostic Systems Limited 237
APPENDIX 1: CORPORATE DIRECTORY 239
LIST OF TABLES AND FIGURES
PAGE
Table 1.1 Amino acids found in proteins 12
Table 1.2 The components of nucleic acids 14
Table 1.3 The genetic code 16
Table 1.4 Survey of thermal cyclers 53
Table 1.5 An overview of DNA amplification systems 57
Table 2.1 Total population incidence
of genetically-determined disease 72
Table 2.2 Annual incidence of genetic disease in the EEC 73
Table 2.3 Some mutations causing cystic fibrosis 89
Table 2.4 Materials costs in Southern blot
DNA diagnostic tests 107
Table 2.5 Commercial companies currently offering
DNA diagnostic products and services for
medical genetics 108
Table 2.1 The ten most common cancers 140
Table 4.1 Retrovirus-associated oncogenes 148
Table 4.2 Non-retroviral oncogenes 150
Table 4.3 Tumours associated with point-mutated oncogenes 151
Table 4.4 Tumours associated with amplified oncogenes 151
Table 4.5 Tumours featuring chromosomal rearrange-
ments and involving known oncogenes 152
Table 4.7 Cervical screening worldwide 167
Table 4.8 Some DNA diagnostic products for HPV typing 168
Table 4.9 Some commercial companies offering
DNA diagnostic cancer-related products 171
Table 5.1 DNA-based pathogen kits 175
Table 6.1 Market for DNA diagnostic services
in monogenic disorders 1992-1998 206
Table 6.2 Market for DNA diagnostic services
in chromosomal disorders 1992-1998 207
Table 6.3 Market for DNA profiling services 1992-1998 208
Table 6.4 Market for cancer-related hybridisation
histochemistry products 1992-1998 209
Table 6.5 Market for other cancer-related
DNA diagnostic analyses 1992-1998 210
Table 6.6 Market for AIDS DNA diagnostic tests 1992-1998 211
Table 6.7 Market for DNA diagnostic tests for
sexually-transmitted diseases 1992-1998 212
Table 6.8 Market for DNA diagnostic tests
for enteric pathogens 1992-1998 213
Table 6.9 Market for DNA diagnostic
mycobacterial tests 1992-1998 214
Table 6.10 DNA diagnostic viral hepatitis
testing market 1992-1998 215
Table 6.11 Market for DNA diagnostic
instrumentation 1992-1998 216
Table 6.12 World DNA diagnostic market by
country and product/service in 1992 217
Table 6.13 World DNA diagnostic market by
country and product/service in 1998 218
Figure 1.1 The polymerase chain reaction (PCR) 49
Figure 2.2 Flow chart for gene tracking 81
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