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1 Chromosomal DNA 1

Ⅰ．The Biochemistry of Nucleic Acids 1

Ⅱ．Levels of DNA Packaging 2

Ⅲ．Centromere 4

Ⅳ．Heterochromatin 4

Ⅴ．Euchromatin 4

Ⅵ．Studying Human Chromosomes 4

Ⅶ．Staining of Chromosomes 5

Ⅷ．Chromosome Morphology 6

Ⅸ．DNA Melting Curve 7

2 Chromosome Replication 9

Ⅰ．General Features 9

Ⅱ．The Chromosome Replication Process 9

Ⅲ．DNA Topoisomerases 11

Ⅳ．The Telomere 12

Ⅴ．DNA Damage 12

Ⅵ．DNA Repair 13

Ⅶ．Clinical Considerations 14

Ⅷ．Summary of Chromosome Replication Machinery 16

3 Meiosis and Genetic Recombination 17

Ⅰ．Meiosis 17

Ⅱ．Genetic Recombination 19

4 The Human Nuclear Genome 22

Ⅰ．General Features 22

Ⅱ．Protein-Coding Genes 23

Ⅲ．RNA-Coding Genes 24

Ⅳ．Epigenetic Control 25

Ⅴ．Noncoding DNA 25

5 The Human Mitochondrial Genome 29

Ⅰ．General Features 29

Ⅱ．The 13 Protein-Coding Genes 29

Ⅲ．The 24 RNA-Coding Genes 29

Ⅳ．Other Mitochondrial Proteins 31

Ⅴ．Mitochondrial Diseases 31

6 Protein Synthesis 33

Ⅰ．General Features 33

Ⅱ．Transcription 33

Ⅲ．Processing the RNA Transcript into mRNA 34

Ⅳ．Translation 35

Ⅴ．Clinical Considerations 37

7 Control of Gene Expression 39

Ⅰ．General Features 39

Ⅱ．Mechanism of Gene Expression 39

Ⅲ．The Structure of DNA-Binding Proteins 41

Ⅳ．Other Mechanisms of Gene Expression 44

Ⅴ．The Lac Operon 46

Ⅵ．The trp Operon 47

8 Mntations of the DNA Sequence 49

Ⅰ．General Features 49

Ⅱ．Silent(Synonymous)Mutations 49

Ⅲ．Non-Silent(Nonsynonymous)Mutations 50

Ⅳ．Loss of Function and Gain of Function Mutations 55

Ⅴ．Other Types of Polymorphisms 56

9 Proto-Oncogenes,Oncogenes,and Tumor-Suppressor Genes 58

Ⅰ．Proto-Oncogenes and Oncogenes 58

Ⅱ．Tumor-Suppressor Genes 60

Ⅲ．Hereditary Cancer Syndromes 62

10 The Cell Cycle 66

Ⅰ．Mitosis 66

Ⅱ．Control of the Cell Cycle 68

11 Molecular Biology of Cancer 71

Ⅰ．The Development of Cancer(Oncogenesis) 71

Ⅱ．The Progression of Cancer 72

Ⅲ．Signal Transduction Pathways 73

12 Cell Biology of the Immune System 77

Ⅰ．Neutrophils(Polys,Segs,or PMNs) 77

Ⅱ．Eosinophils 78

Ⅲ．Basophils 78

Ⅳ．Mast Cells 78

Ⅴ．Monocytes 79

Ⅵ．Macrophages(Histiocytes;Antigen-Presenting Cells) 80

Ⅶ．Natural Killer CDl6+Cell 81

Ⅷ．B Lymphocyte 81

Ⅸ．T Lymphocyte 83

Ⅹ．Immune Response to Exogenous Protein Antigens 85

Ⅺ．Immune Response to Endogenous Antigens(Intracellular Virus or Bacteria) 86

Ⅻ．Cytokines 87

13 Molecular Biology of the Immune System 89

Ⅰ．Clonal Selection Theory 89

Ⅱ．The B Lymphocyte(B Cell) 89

Ⅲ．The T Lymphocyte(T Cell) 93

Ⅳ．Clinical Considerations 95

Ⅴ．Disorders of Phagocytic Function 96

Ⅵ．Systemic Autoimmune Disorders 97

Ⅶ．Organ-Specific Autoimmune Disorders 97

14 Molecular Biology Techniques 100

Ⅰ．Action of Restriction Enzymes 101

Ⅱ．Electrophoresis 103

Ⅲ．The Enzymatic Method of DNA Sequencing 105

Ⅳ．Southern Blotting and Prenatal Testing for Sickle Cell Anemia 107

Ⅴ．Isolating a Human Gene by DNA Cloning 109

Ⅵ．Construction of cDNA Library 111

Ⅶ．Polymerase Chain Reaction 113

Ⅷ．Producing a Protein from a Cloned Gene 115

Ⅸ．Site-Directed Mutagenesis and Knockout Animals 117

Ⅹ．Northern Blot(mRNA) 119

Ⅺ．Western Blot(Protein) 121

Ⅻ．Human Immunodeficiency Virus(HIV)Structure 123

ⅩⅢ．Ligase Chain Reaction(LCR) 125

ⅩⅣ．Flow Cytometry 127

15 Identification of Human Disease Genes 129

Ⅰ．General Features 129

Ⅱ．Identification of a Human Disease Gene Through a Chromosome Abnormality 129

Ⅲ．Identification of a Human Disease Gene Through Pure Transcript Mapping 130

Ⅳ．Identification of a Human Disease Gene Through Large Scale DNA Sequencing 131

Ⅴ．Identification of a Human Disease Gene Through Comparison of Human and Mouse Maps 132

16 Gene Therapy 133

Ⅰ．Gene Therapy 133

Ⅱ．Ex Vivo and In Vivo Gene Therapy 134

Ⅲ．Integration into Host Cell Chromosomes or as Episomes 134

Ⅳ．Viral Vectors Used in Gene Therapy 134

Ⅴ．Nonviral Vectors Used in Gene Therapy 135

Appendix 1:The Genetic Code 137

Appendix 2:Amino Acids 138

Appendix 3:Chromosomal Locations of Human Genetic Diseases 139

Figure Credits 145

Index 147