Publications by Biophoenix' Principals

DNA Diagnostics
Publisher:PJB Publications Ltd
Year of publication:1988
Type of publication:Management report
Publisher's reference (if any):CBS 84
Author(s):Sreten Bogdanovic
Approximate page count:70
Price when published:£250
Remarks:
  1. Page numbers, where given, refer to the draft manuscript (which may differ from the published version).
  2. The copyright in this report is owned by the publisher, to whom any requests for copies should be addressed.
                                  DNA DIAGNOSTICS
         
           A report for Clinica World Medical Device and Diagnostic News
         
                               by Sreten Bogdanovic
         
                                  (August 1988)
         
                               TABLE OF CONTENTS
         
                                                                   PAGE
         
         TABLE OF CONTENTS                                           i
         
         LIST OF TABLES                                              v
         
         CHAPTER 1 : INTRODUCTION AND BACKGROUND                     1
         
         1.1  Scope of this report                                   1
         1.2  Summary of the main applications of DNA analysis       2
         1.3  Nucleic acid structure and function                    3
              1.3.1  Introduction                                    3
              1.3.2  The structure of proteins                       3
              1.3.3  The structure of nucleic acids                  5
              1.3.4  RNA                                             6
              1.3.5  DNA                                             7
              1.3.6  The genetic code                                7
              1.3.7  Function of nucleic acids                       9
                     1.3.7.1  Introduction                           9
                     1.3.7.2  DNA replication                        9
                     1.3.7.3  RNA and transcription                 10
                     1.3.7.4  Processing of RNA                     12
                              1.3.7.4.1 Capping and tailing         12
                              1.3.7.4.2 Splicing                    12
                              1.3.7.4.3 Function of introns         13
                     1.3.7.5  Protein synthesis                     14
         1.4  Classical genetics                                    15
              1.4.1  Genes                                          15
              1.4.2  Linkage                                        17
              1.4.3  Recombination                                  17
              1.4.4  Genetic mapping                                18
              1.4.5  Linkage phase                                  18
              1.4.6  Sex linkage                                    18
              1.4.7  Number of genes in man                         19
              1.4.8  C-value paradox                                19
         1.5  Repetitive DNA                                        20
         1.6  Restriction enzymes                                   20
         1.7  Cloning vectors                                       21
         1.8  DNA probes                                            22
              1.8.1  Description                                    22
              1.8.2  Probe development                              23
         
         CHAPTER 2 : DNA PROBES IN GENETIC DISEASES                 25
         
         2.1  Introduction                                          25
         2.2  Genetic diseases and populations                      25
         2.3  Heterogeneity of many genetic diseases                26
         2.4  Types of genetic disease                              28
         2.5  Detecting genetic disease in utero                    29
              2.5.1  Analysis of amniotic fluid supernatant         29
              2.5.2  Enzyme assays in cultured amniocytes           29
              2.5.3  Chorionic villus sampling (CVS)                30
              2.5.4  Analysis of foetal blood and other tissues     30
              2.5.5  Ultrasound                                     31
              2.5.6  DNA analysis                                   31
         2.6  Methodology of DNA diagnosis                          31
              2.6.1  Introduction                                   31
              2.6.2  Gene tracking                                  32
              2.6.3  Restriction fragment length polymorphisms
                     (RFLPs)                                        33
              2.6.4  Highly polymorphic markers                     34
              2.6.5  Haplotypes                                     35
         2.7  Survey of important inherited diseases                36
              2.7.1  Alpha-1-antitrypsin deficiency                 36
              2.7.2  Congenital adrenal hyperplasia                 37
              2.7.3  Cystic fibrosis                                37
              2.7.4  Duchenne muscular dystrophy                    37
              2.7.5  The haemophilias                               38
              2.7.6  Huntingdon's disease                           38
              2.7.7  Neurofibromatosis                              38
              2.7.8  Myotonic dystrophy                             39
              2.7.9  Phenylketonuria                                39
              2.7.10 Polycystic kidney disease                      39
              2.7.11 The haemoglobinopathies                        39
              2.7.12 The fragile-X syndrome                         40
         2.8  Likely market sizes and nature                        40
         2.9  Report of a regional DNA diagnostics centre           41
         
         CHAPTER 3: DNA PROBES IN CANCER                            43
         
         3.1  Introduction                                          43
         3.2  Incidence of cancer                                   43
         3.3  The genetics of cancer                                44
         3.4  Anti-oncogenes                                        45
         3.5  Oncogenes and viruses                                 46
         3.6  Gene probes in cancer                                 48
              3.6.1  Introduction                                   48
              3.6.2  bcr analysis                                   48
              3.6.3  Other translocation malignancies               49
              3.6.4  B/T cell DNA analysis                          49
         3.7  Cervical cancer                                       50
         3.8  Conclusions                                           50
         3.9  Likely market sizes and nature                        51
         
         CHAPTER 4: DNA PROBES AND INFECTIOUS DISEASE               52
         
         4.1  Introduction                                          52
         4.2  Methodology                                           52
         4.3  Kit availability and commercialisation                53
         4.4  Survey of specific bacterial pathogens                54
              4.4.1  Bacteroides species                            54
              4.4.2  Campylobacter                                  55
              4.4.3  Chlamydia                                      55
              4.4.4  Gonorrhoea                                     55
              4.4.5  Legionellosis                                  55
              4.4.6  Leptospirosis                                  56
              4.4.7  Mycobacteria                                   56
              4.4.8  Mycoplasmas                                    56
              4.4.9  Salmonellae                                    56
         4.5  Survey of specific viral pathogens                    57
              4.5.1  Adenovirus                                     57
              4.5.2  Cytomegalovirus                                57
              4.5.3  Human immunodeficiency virus                   57
              4.5.4  Hepatitis                                      58
              4.5.5  Rotavirus                                      59
         4.6  Survey of specific parasitic pathogens                59
              4.6.1  Leishmaniasis                                  59
              4.6.2  Plasmodium                                     60
              4.6.3  Tapeworms (Taeniids)                           60
         4.7  Immunoassays and DNA probes                           60
         4.8  Likely market sizes and nature                        61
         
         CHAPTER 5: OTHER APPLICATIONS OF DNA PROBES                62
         
         5.1  Disorders with a major genetic component              62
              5.1.1  Introduction                                   62
              5.1.2  Alzheimer's disease                            62
              5.1.3  Coronary artery disease                        63
              5.1.4  Diabetes mellitus                              64
              5.1.5  Immunological diseases                         64
              5.1.6  Psychiatric disorders                          64
                     5.1.6.1  Schizophrenia                         64
                     5.1.6.2  Manic-depressive psychosis            65
              5.1.7  Market potential                               65
         5.2  DNA fingerprinting                                    66
              5.2.1  Introduction                                   66
              5.2.2  Applications                                   67
              5.2.3  Current situation                              67
         5.3  Pre-employment screening                              68
         5.4  Plant and animal diagnostics                          69
         5.5  Security applications                                 69
         
         CHAPTER 6 : PRESENT STATUS OF THE DNA DIAGNOSTIC MARKET    70
         
         6.1  Introduction                                          70
         6.2  Company profiles                                      70
              6.2.1  Abbott Laboratories                            71
              6.2.2  Amgen                                          71
              6.2.3  Amersham International plc                     71
              6.2.4  Battelle Memorial Institute                    71
              6.2.5  Biotal Limited                                 72
              6.2.6  Biotechnica International                      72
              6.2.7  British Bio-technology Limited                 72
              6.2.8  California Biotechnology                       72
              6.2.9  Cetus                                          73
              6.2.10 Chiron                                         73
              6.2.11 Collaborative Research                         73
              6.2.12 Enzo Biochem                                   74
              6.2.13 Gen Probe                                      74
              6.2.14 Imperial Chemical Industries/Cellmark
                     Diagnostics                                    74
              6.2.15 Integrated Genetics/Gene Trak Systems          74
              6.2.16 Johnson & Johnson/Ortho Diagnostics            75
              6.2.17 Lifecodes                                      75
              6.2.18 Molecular Biosystems                           75
              6.2.19 Oncor                                          75
              6.2.20 Oncogene Sciences                              76
              6.2.21 Other Companies                                76
         
         
         CHAPTER 7 : FUTURE DEVELOPMENTS IN DNA DIAGNOSTICS         78
         
         7.1  Labelling techniques                                  78
         7.2  Automation                                            80
         7.3  New electrophoretic techniques                        80
         7.4  Site-directed DNA cleavage                            81
         7.5  Sequencing the human genome                           81
         7.6  DNA sensors                                           81
         
         APPENDIX: ADDRESSES OF COMPANIES MENTIONED                 83
         
         

                               LIST OF TABLES
         
         
         TABLE       TITLE                                         PAGE
         
         
         1.1         Amino acids found in proteins                   4
         
         1.2         The components of nucleic acids                 5
         
         1.3         The genetic code                                8
         
         2.1         Total population incidence of genetically-
                     determined disease                             28
         
         2.2         Mendelian disorders now detectable by DNA
                     methods                                        31
         
         2.3         Flow chart for gene tracking                   36
         
         2.4         World market for prenatal DNA diagnostics      41
         
         3.1         Incidence of 12 cancers of selected sites
                     in 1975                                        44
         
         3.2         The most well-characterised oncogenes          47
         
         3.3         Tumours displaying oncogene amplification      47
         
         3.4         Tumours containing activated ras oncogenes     48
         
         3.5         World oncology DNA probe market                51
         
         4.1         DNA diagnostic kits having FDA approval at
                     August 1988                                    54
         
         


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