Genomics : applications in human biology / Sandy B. Primrose, Richard M. Twyman. — Malden, MA : Blackwell Pub., c2004.—(63.141/P953)

Contents

        Full Contents
    
    CHAPTER ONE: Biotechnology and genomics in medicine 1
    Introduction 1
    Recombinant DNA technology 2
     The central importance of cloning 2
     Identification and cloning of specitic genes 5
     Functional characterization of cloned genes 9
    From recombinant DNA to molecular medicine 10
     The use of DNA sequences as diagnostic tools 11
     The production of therapeutic proteins 11
    Gene medicine 14
    Disease models 15
    The impact of genomics on medicine 15
    The new molecular medicine 17
    Outline of this book 18
    Further reading 19
    CHAPTER TWO: An overview of genomics 20
    Introduction 20
    A review of progress: the Human Genome Project 21
     Breakthroughs in genetic mapping 23
     Breakthroughs in physical mapping 25
     Sequencing strategies 28
     Gcnome annotation 31
    The future: functional genomics 35
     Sequence comparison and comparative genomics 37
     Transcriptomics: global analysis of mRNA 40
     Proteomics: global analysis of proteins 45
     Technology platforms for proteome separation 47
     Protein characterization by mass spectrometry 49
     Applications of expression proteomics 51
     Technology platforms for interaction proteomics 51
    Mutational genomics 55
    Further reading 57
    CHAPTER THREE: Genomics and the challenge of infectious disease 60
    Microorganisms causing disease 60
    Where do new diseases come from? 63
    Identifying the causative agent of a disease 65
    Molecular epidemiology 68
    Host resistance to infection 70
    Understanding bacterial pathogenicity 70
     Pathogenicity islands 72
    Comparative genomics and genome plasticity 73
    Combating infectious disease 75
     Novel routes to vaccines 76
     Genomics and the development of new antibacterial agents 78
     Combating fungal infections 81
     Progress in tackling protozoan diseases 82
     Developing antiviral drugs 86
    Further reading 89
    CHAPTER FOUR: Analyzing and treating genetic diseases 90
    Genetic disease in context 90
    Detecting single gene disorders 91
    Treating sin gle gene disorders 96
    Finding genes for monogenic diseases and determining gene function 98
     Positional cloning 99
     The candidate gene approach 100
    Analysis of polygenic disorders 102
     Model-free linkage analysis 102
     Linkage disequilibrium mapping 103
    Haplotypes 105
    The major histocompatibility complex 106
    Individual responses to drugs (pharmacogenomics) 109
    Further reading 110
    CHAPTER FIVE: Diagnosis and treatment of cancer 112
    Introduction 112
     The molecular basis of cancer 112
    The impact of genomics on cancer research 116
    New methods for the diagnosis of cancer 119
    New approaches to cancer therapy 122
     Radiotherapy 122
     Chemotherapy 123
     Biotherapy 127
     New therapeutic targets 129
    Further reading 129
    CHAPTER SIX: The large scale production of Biopharmaceuticals 131
    Overview 131
    The generation of monoclonal antibodies 132
     Radioimmunotherapy and diagnostic imaging 135
     Other modified antibodies 137
    The large scale culture of microorganisms 137
    The large scale culture of animal cells 140
    Expression systems 144
    Downstream processing 145
    Using gene manipulation to facilitate downstream processing of Biopharmaceuticals 148
    The quality ofbiopharmaceuticals 149
    Good manufacturing practice 153
    Alternative production systems 154
    Further reading 155
    CHAPTER SEVEN: Genomics and the development of new chemical entities 157
    Introduction: how drugs are developed 157
    High-throughput screening 159
    Target validation and animal models 163
    Combinatorial chemistry 167
    Dynamic combinatorial libraries 170
    Virtual screening 171
    Combinatorial biosynthesis and chemobiosynthesis 172
    Drug metabolism 174
    Toxicogenomics 175
    Further reading 176
    CHAPTER EIGHT: Gene and cell therapies 178
    Introduction 178
    Gene therapy 179
    Gene delivery strategies 181
    Gene delivery mechanisms 182
    Case studies 186
    Nucleic acids as drugs 190
     Antisense drugs 190
     Ribozyme drugs 191
     The potential of short interfering RNAs 191
     Aptamer drugs 193
     Gene medicine for infectious diseases: HIV 193
    DNA vaccines 194
    Disease models 195
     Models of single gene disorders 195
     Models of complex disorders 199
    Cell therapy 199
     Stem cells and cloning 200
     Organ transplants 202
    Further reading 203