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Bibliografická citace

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BK
2nd ed.
New York : John Wiley & Sons, c2000
xviii,876 s. : il.

objednat
ISBN 0-471-29800-X (váz.)
Obsahuje ilustrace, bibliografické citace, údaje o autorech, předmluvu, úvod, glosář, rejstřík
Genetika - učebnice vysokošk.
000086680
Brief Contents // Ŕit itiifödiidion to the Science of Genetics Chapter 1 The Science of Genetics 3 Chapter 2 Reproduction as the Basis of Heredity 22 Classical Genetic Analysis // Chapter 3 Mendelismi The Basic Principles of Inheritance 52 Chapter 4 Extensions of Mendelism 72 Chapter 5 Inheritance of Complex Traits 91 Chapter 6 The Chromosomal Basis of Mendelism 116 Chapter 7 Variation in Chromosome Number and Structure 13S Chapter S Linkage, Crossing Over, and Chromosome Mapping in Eukaryotes 167 Chapter 9 Advanced Linkage Analysis 190 The Molecular Biology of Genes // Chapter 10 DNA and the Molecular Structure of Chromosomes 219 Chapter 11 Replication of DNA and Chromosomes 255 Chapter 12 Transcription and RNÁ Processing 292 Chapter 13 Translation and the Genetic Code 326 Chapter 14 Mutation, DNA Repair, and Recombination 358 Chapter 15 Definitions of the Gene 397 The Genetics of Viruses, Bacteria, Transposons, and Eukaryotic Organdies Chapter 16 The Genetics of Viruses 429 Chapter 17 The Genetics of Bacteria 453 Chapter 18 Transposable Genetic Elements 476 Chapter 19 The Genetics of Mitochondria and Chloroplasts 496 Molecular Genetic Analysis // Chapter 20 The Techniques of Molecular Genetics 517 Chapter 21 Genomics 553 // Chapter 22 Molecular Analysis of Genes and Gene Products 585 // The Regulation of Gene Expression // Chapter 23 Regulation of Gene Expression in Prokaryotes and Their Viruses 615 Chapter 24 Regulation of Gene Expression in Eukaryotes 644 The Genetic Control
of Biological Processes // Chapter 25 The Genetic Control of Animal Development 675 Chapter 26 The Genetic Control of Behavior 710 Chapter 27 The Genetic Control of the Vertebrate Immune System 728 Chapter 28 The Genetic Basis of Cancer 750 The Genetics of the Evolutionary Process // Chapter 29 Population and Evolutionary Genetics 774 Epilogue by James F. Crow 807 // Contents // An Introduction to the Science of Genetics A Conversation with Valery N. Soyfer 1 // 1 THE SCIENCE OF GENETICS 3 A Passion for Experimenting 3 Classical and Molecular Genetics 4 Genetics in the News 5 // Genetics and Medicine 7 Genetics and Modern Agriculture 11 Genetics and Society 15 The Principles of Genetics: An Overview 16 DNA; The Genetic Material 17 DNA Replication; Transmission of Genetic Information 17 // Gene Expression: Control of Growth and Development 18 // Mutation; Changes in the Genetic Material over Time 20 // Human Genetics Sidelight: Hemophilia: // Successful Treatment of a Once Deadly Disorder 10 // 2 REPRODUCTION AS THE BASIS OF HEREDITY 22 // An Acciderit in Cell Division 22 The Cell as the Basic Unit of Fife 23 The Prokaryotic Cell 23 The Eukaryotic Cell 24 The Chromosome; An Overview 27 The Cell Cycle 28 Cell Division: Mitosis 28 Cell Division; Meiosis 32 Meiotic Abnormalities 37 The Evolutionary Significance of Meiosis 37 The Formation an4 Union of Gametes 37 Oogenesis; The Formation of the Egg 38 Spermatogenesis; The Formation of Sperm 39 Gamete Formation in Plants 40 The Life
Cycles of Some Genetically Important Organisms 40 // Neurospora crassa; The Simple Bread Mold 41 Saccharomyces cerevisiae; Baker’s Yeast 43 Zea mays; Corn 44 // Drosophila melanogaster; The Fruit Fly 45 Humans 46 // Technical Sidelight: Dolly: To Clone or Not to Clone 42 // Classical Genetic Analysis A Conversation with Joseph G. Gall 50 // 3 MENDELISM: // THE BASIC PRINCIPLES OF INHERITANCE 52 The Birth of Genetics: A Scientific Revolution 52 Mendel’s Study of Heredity 53 // Mendel’s Experimental Organism, the Garden Pea 53 // Monohybrid Crosses: The Principles of Dominance and Segregation 54 Dihybrid Crosses: The Principle of Independent Assortment 56 Applications of Mendel’s Principles 58 The Punnett Square Method 58 The Forked-Line Method 59 The Probability Method 59 Formulating and Testing Genetic Hypotheses 61 The Chi-Square Test 62 // Mendelian Principles in Human Genetics 64 Pedigrees 64 // Mendelian Segregation in Human Families 65 Genetic Counseling 66 Technical Sidelight: The Multiplicative and Additive Rules of Probability 61 Technical Sidelight: Binomial Probabilities 67 // 4 EXTENSIONS OF MENDELISM 72 Genetics Grows Beyond Mendels // Monastery Garden 72 Allelic Variation and Gene Function 73 // Incomplete Dominance and Codominance 73 Multiple Alleles 74 Allelic Series 75 // Testing Gene Mutations for Allelism 75 Variation Among the Effects of Mutations 76 Genes Function to Produce Polypeptides 77 Why Are Some Mutations Dominant and Others Recessive? 79 Gene Action:
From Genotype to Phenotype 80 Influence of the Environment 80 Environmental Effects on the Expression of Human Genes 81 Penetrance and Expressivity 81 Gene Interactions 82 // Contents xi // Čpistŕsis 84 Pleiotropy 86 // The Genetic Basis of Continuous Phenotypic // Variation 86 // Historical Sidelight: Genetic Symbols: Evolution in a Dynamic Science 78 Human Genetics Sidelight: The Hapsburg Jaw: // A Dominant Trait with Incomplete Penetrance and Variable Expressivity in the European Nobility 83 // 5 INHERITANCE OF COMPLEX TRAITS 91 // Cardiovascular Disease: A Combination of Genetic and Environmental Factors 91 Complex Patterns of Inheritance 92 Quantitative Traits 92 Threshold Traits 95 Statistics of Quantitative Genetics 97 Frequency Distributions 97 The Mean and the Modal Class 98 The Variance and the Standard Deviation 98 Analysis of Quantitative Traits 99 The Multiple Factor Hypothesis 99 Partitioning the Phenotypic Variance 100 Broad-Sense Heritability 101 Narrow-Sense Heritability 102 Predicting Phenotypes 103 Artificial Selection 104 Quantitative Trait Loci 105 Inbreeding and the Resemblance Between Relatives 107 // The Effects of Inbreeding 107 Genetic Analysis of Inbreeding 109 Correlations Between Relatives 112 Human Genetics Sidelight: Genetic Counseling and Multifactoral Traits 96 // Technical Sidelight: Artificial Selection for Body Size 106 // 6 THE CHROMOSOMAL BASIS OF MENDELISM 116 // Sex, Chromosomes, and Genes 116 Chromosomes 117 // Chromosome Number 117 Sex
Chromosomes 117 The Chromosome Theory of Heredity 119 // Experimental Evidence Linking the Inheritance of Genes to Chromosomes 119 Chromosomes as Arrays of Genes 120 Nondisjunction as Proof of the Chromosome Theory 121 The Chromosomal Basis of Mendel’s Principles of Segregation and Independent Assortment 123 Sex-Linked Genes in Human Beings 126 Hemophilia, an X-Linked Blood-Clotting Disorder 126 // Color Blindness, an X-Linked Vision Disorder 127 The Fragile X Syndrome and Mental Retardation 127 // Genes on the Human Y Chromosome 128 Genes on Both the X and Y Chromosomes 128 Sex Chromosomes and Sex Determination 128 Sex Determination in Human Beings 129 Sex Determination in Drosophila 130 Sex Determination in Other Animats 131 Dosage Compensation of X-Linked Genes 132 Hyperactivation of X-Linked Genes in Male Drosophila 133 Inactivation of X-Linked Genes in Female Mammals 133 Historical Sidelight: Drosophila, T H. Morgan, and "The Fly Room" 122 // 7 VARIATION IN CHROMOSOME NUMBER AND STRUCTURE 138 // Chromosomes AgriculturOi and Civilization 138 Cytological Techniques 139 // Analysis of Mitotic Chromosomes 139 The Human Karyotype 141 Cytogenetic Variation: An Overview 142 Polyploidy 143 // Sterile Polyploids 144 Fertile Polyploids 145 Chromosome Doubling and the Origin of Polyploids 146 // Experimental Production of Polyploids 147 Tissue-Specific Polyploidy and Polyteny 148 Aneuploidy 149 // Trisomy in Human Beings 150 Monosomy 152 // Deletions and Duplications of Chromosome
Segments 153 // Rearrangements of Chromosome Structure: // An Overview 156 Inversions 156 Transloca tions 157 Compound Chromosomes // and Robertsonian Translocations 159 Phenotypic Effects of Chromosome Rearrangements 162 // Human Genetics Sidelight: Amniocentesis and Chorionic Biopsy: Procedures to Detect Aneuploidy in Human Fetuses 154 // Technical Sidelight: Oenothera: Chromosome Rings and Other Things 160 // 8 LINKAGE, CROSSING OVER, AND CHROMOSOME MAPPING IN EUKARYOTES 167 // The World’s First Chromosome Map 167 Linkage, Recombination, and Crossing Over 168 // xii Contents // Exceptions to the Mendelian Principle of Independent Assortment 168 Frequency of Recombination as a Measure of Linkage Intensity 169 Crossing Over as the Physical Basis of Recombination 171 Evidence That Crossing Over Causes Recombination 172 // Chiasmata and the Time of Crossing Over 173 Chromosome Mapping 174 Crossing Over as a Measure of Genetic Distance 174 Recombination Mapping // with a Two-Point Testcross 175 Recombination Mapping // with a Three-Point Testcross 176 Recombination Frequency and Genetic Map Distance 180 Chiasma Frequency and // Genetic Map Distance 182 Genetic Distance and Physical Distance 182 Recombination and Evolution 183 // Evolutionary Significance of Recombination 183 Suppression of Recombination by Inversions 184 Genetic Control of Recombination 185 Human Genetics Sidelight: Evidence for Linkage Between the Genes for Hemophilia and Color Blindness 178 // 9 ADVANCED LINKAGE
ANALYSIS 190 // Huntington’s Disease: A Challenge in Gene Mapping 190 // Detection of Linkage in Experimental Organisms 191 Tetrad Analysis to Detect Linkage in Fungi 191 Balancer Chromosome Technique to Assign a Gene to a Chromosome in Drosophila 194 Specialised Mapping Techniques 196 // Centromere Mapping with Ordered Tetrads in Neurospora 196 Cytogenetic Mapping with Deletions and Duplications in Drosophila 198 Linkage Analysis in Humans 201 // Detection of Linked Loci by Pedigree Analysis 201 Somatic-Cell Genetics: An Alternative Approach to Gene Mapping 204 The Human Gene Map 2? Technical Sidelight: The Relationship Between Genes and Bands in the Drosophila Polytene X Chromosome 202 // The Molecular Biology of Genes A Conversation with Edward B. Lewis 217 // 10 DNA AND THE MOLECULAR STRUCTURE OF CHROMOSOMES 219 // Discovery of Nuclein 219 // Functions of the Genetic Material 220 Proof That Genetic Information Is Stored in DNA 220 // Discovery of Transformation in Bacteria 220 Proof That DNA Mediates Transformation 222 Proof That DNA Carries the Genetic Information in Bacteriophage T2 222 Proof That RNA Stores the Genetic Information in Some Viruses 224 The Structures of DNA and RNA 225 // Nature of the Chemical Subunits in DNA and RNA 225 // DNA Structure: The Double Helix 225 DNA Structure: Alternate Forms of the Double Helix 230 // DNA Structure: Negative Supercoils in Vivo 232 Chromosome Structure in Prokaryotes and Viruses 233 // Chromosome Structure in Eukaryotes 234
Chemical Composition of Eukaryotic Chromosomes 235 // One Large DNA Molecule per Chromosome 236 Three Levels of DNA Packaging in Eukaryotic Chromosomes 239 Centromeres and Telomeres 242 Eukaryotic Genomes: Repeated DNA Sequences 246 // Detection of Repeated Sequences: // DNA Renaturation Kinetics 246 Localization of Repeated DNA Sequences in Chromosomes 249 // Repeated Sequences in the Human Genome 251 Technical Sidelight: DNA Renaturation Kinetics 248 // 1 1 REPLICATION OF DNA AND CHROMOSOMES 255 // Monozygotic Twins: Are They Identical? 255 Basic Features of DNA Replication In Vivo 256 Semiconservative Replication 256 Visualization of Replication Forks by Autoradiography 259 Unique Origins of Replication 262 Bidirectional Replication 263 DNA Polymerases and DNA Synthesis In Vitro 264 Discovery of DNA Polymerase I in Escherichia coli 266 Multiple DNA Polymerases 267 DNA Polymerase III: The Replicase in Escherichia coli 269 Proofreading Activities of DNA Polymerases 270 The Complex Replication Apparatus 271 Continuous Synthesis of One Strand; // Discontinuous Synthesis of the Other Strand 272 // Côfttóttš xěii // Covalent Closure of Nicks in DNA by DNA Ligase 273 // Initiation of DNA Chains with RNA Primers 273 Unwinding DNA with Helicases, // DNA-Binding Proteins, and Topoisomerases 275 The Replication Apparatus: Prepriming Proteins, Primosomes, and Replisomes 277 Rolling-Circle Replication 280 Unique Aspects // of Eukaryotic Chromosome Replication 280 The Cell Cycle 281
// Multiple Replicons per Chromosome 281 Two DNA Polymerases at a Single Replication Fork 283 Duplication of Nucleosomes at Replication Forks 284 Telomerase: Replication of Chromosome Termini 284 // Telomere Length and Aging in Humans 285 Technical Sidelight: Cesium Chloride Equilibrium Density-Gradient Centrifugation and Sucrose Velocity Density-Gradient Centrifugation: // Two Important and Distinct Tools 260 // 12 TRANSCRIPTION AND RNA PROCESSING 292 // Storage and Transmission of Information with Simple Codes 292 The Genetic Control of Metabolism: // An Overview 293 Transfer of Genetic Information: // The Central Dogma 294 // Transcription and Translation 294 Four Types of RNA Molecules 295 The Process of Gene Expression 298 An mRNA Intermediary 298 General Features of RNA Synthesis 300 Transcription in Prokaryotes 302 // RNA Polymerase: A Complex Enzyme 302 Initiation of RNA Chains 303 Elongation of RNA Chains 303 Termination of RNA Chains 304 Concurrent Transcription, Translation, and mRNA Degradation 304 Transcription and RNA Processing in Eukaryotes 305 // Three RNA Polymerases/Three Sets of Genes 307 Initiation of RNA Chains 307 RNA Chain Elongation and the Addition of 5’ Methyl Guanosine Caps 308 Termination by Chain Cleavage and the Addition of 3’ Poly (A) Tails 310 RNA Editing: Altering the Information Content of mRNA Molecules 310 // Interrupted Genes in Eukaryotes: Exons and Introns 312 // Early Evidence for Noncoding Sequences in Eukaryotic GeUeš 313 Some Very Large
Eukaryotic Gštišš 313 Introns: Biological Significance? 316 Removal of Intron Sequences by RNA Spiking 317 tRNA Precursor Splicing: Unique Nuclease and Ligase Activities 318 Autocatalytic Splicing 319 Pre-mRNA Splicing: snRNAs, snRNPs and the Spliceosome 320 Technical Sidelight: An mRNA Intermediary: // Evidence from Phage-Infected E. coli 299 // 13 TRANSLATION AND THE GENETIC CODE 326 // Sickle-Cell Anemia: Devastating Effecti of a Single Base-Pair Change 326 Protein Structure 327 // Polypeptides: Twenty Different Amino Acid Subunits 327 Proteins: Complex Three-Dimensional Structures 329 // Protein Synthesis: Translation 331 Overview of Protein Synthesis 331 Components Required for Protein Synthesis: Ribosomes and Transfer RNAs 332 Translation: The Synthesis of Polypeptides Using mRNA Templates 337 The Genetic Code 344 // Properties of the Genetic Code: An Overview 344 Three Nucleotides per Codon 344 Deciphering the Code 346 Initiation and Termination Codons 349 A Degenerate and Ordered Code 350 A Nearly Universal Code 351 Codon-tRNA Interactions 352 // Recognition of Codons by tRNAs: // The Wobble Hypothesis 352 Suppressor Mutations That Produce tRNAs with Altered Codon Recognition 352 In Vivo Confirmation of the Nature of the Genetic Code 354 Technical Sidelight: Cracking the Genetic Code: // Synthetic mRNAs 348 Historical Sidelight: Hannah Bernstein and the Amber Codon 351 // 14 MUTATION, DNA REPAIR, // AND RECOMBINATION 358 // Xeroderma Pigmentosum: Defective Repair of
Damaged DNA in Humans 358 Mutation: Source of the Genetic Variability Required for Evolution 359 // xiv Contents // Mutation: Basic Features of the Process 360 Mutation: Somatic or Germinal 360 Mutation: Spontaneous or Induced 360 Mutation: Usually a Random, // Nonadaptive Process 361 Mutation: A Reversible Process 362 Mutation: Phenotypic Effects 363 // Mutations with Phenotypic Effects: Usually Deleterious and Recessive 364 Effects of Mutations in Human Globin Genes 364 Mutation in Humans: Blocks in Metabolic Pathways 366 Conditional Lethal Mutations: Powerful Tools for Genetic Studies 369 Muller’s Demonstration That X Rays Are Mutagenic 370 The Molecular Basis of Mutation 371 Mutations Induced by Chemicals 373 Mutations Induced by Radiation 378 Mutations Induced by Transposable Genetic Elements 380 // Expanding Trinucleotide Repeats and Inherited Human Diseases 381 Screening Chemicals for Mutagenicity: // The Ames Test 381 Dbi A Repair MecYianisrrvs 3S3 Light-Dependent Repair 383 Excision Repair 383 Mismatch Repair 385 Postreplication Repair 386 The Error-Prone Repair System 387 Inherited Human Diseases with Defects in DNA Repair 387 DNA Recombination Mechanisms 388 Recombination: Cleavage and Rejoining of DNA Molecules 388 // Gene Conversion: DNA Repair Synthesis Associated with Recombination 390 Human Genetics Sidelight: Tay-Sachs Disease, // A Childhood Tragedy 367 // 15 DEFINITIONS OF THE GENE 397 // Sir Archibald Garrod and Human Inborn Errors // of Metabolism 397 // Evolution
of the Concept of the Gene: Summary 398 Evolution of the Concept of the Gene: Function 401 Mendel: Constant Factors Controlling Phenotypic Traits 401 Garrod: One Mutant Gene-One Metabolic Block 402 Early Evidence That Enzymes Are Controlled by Genes 402 // Beadle and Tatum: One Gene-One Enzyme 404 One Gene-One Polypeptide 406 Evolution of the Concept of the Gene: Structure 406 // The Pre-1940 Beads-on-a-String Concept 406 Discovery of Recombination Within the Gene 407 Recombination Between Adjacent Nucleotide Pairs 407 // Colinearity Between the Coding Sequence of a Gene and Its Polypeptide Product 408 A Genetic Definition of the Gene 410 // The Complementation Test as an Operational Definition of the Gene 411 Intragenic Complementation 415 Limitations on the Use // of the Complementation Test 418 Complex Gene-Protein Relationships 419 Alternate Pathways of Transcript Splicing: // Protein Isoforms 420 Assembly of Genes During Development: // Human Antibody Chains 420 Human Genetics Sidelight: Human Inborn Errors of Metabolism 399 // The Genetics of Viruses, Bacteria, Transposons, and Eukaryotic Organelles // A Conversation with Gisela Mosig 427 // 16 THE GENETICS OF VIRUSES 429 A Killer Unleashed 419 The Discovery of Viruses 430 The Origin of Viruses 431 The Structure and Life Cycle of a Bacterial Virus 432 Mapping the Bacteriophage Genome 434 Phage Phenotypes 434 Genetic Recombination in Phage 435 Genetic Fine Structure 436 Deletion Mapping 437 T4: A Circular Genetic Map // but
a Linear Chromosome 441 Genes-Within-Genes: Bacteriophage ??174 443 HIV: A Eukaryotic Virus 445 What Is AIDS? 445 The Structure of HIV 445 The HIV Life Cycle 445 The HIV Genome 449 The Course of HIV Infection 449 // 1 7 THE GENETICS OF BACTERIA 453 // Drug Resistance and Gene Transfer in Bacteria 453 Genetic Exchange in Bacteria: An Overview 454 Mutant Phenotypes in Bacteria 455 Basic Test for Transformation, Conjugation, and Transduction 456 Transformation 457 // The Process of Transformation 457 Transformation and Gene Mapping 458 Conjugation 460 // Contents XV // The Discovery of Conjugation 460 F+ X F~ Mating 461 Hfr Conjugation 461 F’ Conjugation or Sexduction 463 Conjugation and Gene Mapping 464 Mapping Closely Linked Genes 465 On the Origin of Plasmids 466 Transduction 467 // The Discovery of Transduction 467 Generalized Transduction 467 Specialized Transduction 467 Transduction and Gene Mapping 470 The Evolutionary Significance of Sexuality in Bacteria 472 // 18 TRANSPOSABLE GENETIC ELEMENTS 476 Maize: A Staple Crop with a Cultural Heritage 476 Transposable Elements in Bacteria 477 // IS Elements 477 Composite Transposons 479 Tn3 Elements 480 The Medical Significance // of Bacterial Transposons 481 Transposable Elements in Eukaryotes 481 Ac and Ds Elements in Maize 482 P Elements and Hybrid Dysgenesis in Drosophila 484 mariner, an Ancient and Widespread Transposon 487 Retrotransposons 487 // Retroviruslike Elements 487 Retroposons 490 // The Genetic and Evolutionary Significance
of Transposable Elements 491 // Transposons and Genome Organization 491 Transposons and Mutation 492 Evolutionary Issues Concerning Transposable Elements 493 Historical Sidelight: Barbara McClintock, // The Discoverer of Transposable Elements 478 Technical Sidelight: Genetic Transformation ?/Drosophila with P Elements 488 // 19 THE GENETICS // OF MITOCHONDRIA AND CHLOROPLASTS 496 Mitochondria, Chloroplasts, and the Biological Energy Wheel 496 The Classical Genetics of Organelles 497 Leaf Variegation in Plants 497 Cytoplasmic Male Sterility in Maize 499 Antibiotic Resistance in Chlamydomonas 500 Metabolic Defects in Yeast 502 The Molecular Genetics of Mitochondria 503 Mitochondrial DNA 503 Expression of Mitochondrial Genes 505 // Interplay Between Mitochondrial and Nuclear Gene Products 506 Mitochondrial DNA and Human Disease 506 The Molecular Genetics of Chlofopläštš 507 Chloroplast DNA 507 Chloroplast Biogenesis 507 The Origin and Evolution // of Mitochondria and Chloroplasts 509 Eukaryotic Organelles as Endosymbionts 509 The Evolution of Mitochondria and Chloroplasts 512 // Human Genetics Sidelight: Using Mitochondrial DNA to Study Human Evolution 510 // Molecular Genetic Analysis A Conversation with Nancy Wexler SIS // 20 THE TECHNIQUES OF MOLECULAR GENETICS 517 Treatment of Pituitary Dwarfism // with Human Growth Hormone 517 Basic Techniques Used to Clone Genes 518 // The Discovery of Restriction Endonucleases 518 The Production of Recombinant DNA Molecules In Vitro 521
// Amplification of Recombinant DNA Molecules in Cloning Vectors 522 // Construction and Screening of DNA Libraries 525 Construction of Genomic Libraries 526 Construction of cDNA Libraries 528 Screening DNA Libraries for Genes of Interest 528 Biological and Physical Containment of Recombinant DNA Molecules 529 The Manipulation of Cloned DNA Sequences In Vitro 531 // Phagemids: The Biological Purification of DNA Single Strands 531 In Vitro Site-Specific Mutagenesis 534 The Molecular Analysis of DNA, RNA, and Protein 535 Analysis of DNAs // by Southern Blot Hybridizations 536 Analysis of RNAs // by Northern Blot Hybridizations 539 Analysis of Proteins // by Western Blot Techniques 540 The Molecular Analysis of Genes and Chromosomes 541 Amplification of DNAs // by the Polymerase Chain Reaction (PCR) 541 Physical Maps of DNA Molecules Based on Restriction Enzyme Cleavage Sites 543 Nucleotide Sequences: The Ultimate Fine Structure Maps 543 // xvi Contents // Human Genetics Sidelight: Treatment of Diabetes Mellitus with Human Insulin Produced in Bacteria 520 // Technical Sidelight: Detection of a Mutant Gene Causing Cystic Fibrosis by Southern Blot Analysis 538 // 21 GENOMICS 553 // Human Gene Prospecting in Iceland 553 Genomics: An Overview 555 Correlated Genetic, Cytological, // and Physical Maps of Chromosomes 555 Restriction Fragment-Length Polymorphism (RFLP) and Microsatellite Maps 558 Cytogenetic Maps 562 Physical Maps and Clone Banks 562 Map Position-Based Cloning of Genes 564
Chromosome Walks 564 Chromosome Jumps 566 The Human Genome Project 567 Bacterial Genomes 567 // The Saccharomyces cerevisiae (Yeast) Genome 569 The Human Genome 571 // RNA and Protein Assays of Genome Function 573 Expressed Sequences 573 Array Hybridizations arid Gene Chips 573 ?? of Green Fluorescent Protein as a Reporter of Protein Synthesis 574 Evolution of Genomes 577 // Genome Evolution in the Cereal Grasses 577 Genome Evolution in Mammals 579 Human Genetics Sidelight: The Race to Sequence the Human Genome 556 // 22 MOLECULAR ANALYSIS OF GENES AND GENE PRODUCTS 585 // Detection of the Tay-Sacbs Mutation in Eight-Cell Pre-embryos 585 Use of Recombinant DNA Technology to Identify Human Genes 586 Huntington’s Disease 586 Cystic Fibrosis 590 // Molecular Diagnosis of Human Diseases 593 DNA Fingerprints 594 Paternity Tests 595 Forensic Applications 595 Human Gene Therapy 597 Production of Eukaryotic Proteins in Bacteria 601 Human Growth Hormone 601 Proteins with Industrial Applications 602 Transgenic Plants and Animals 603 // Transgenic Animals: Microinjection of DNA into Fertilized Eggs 603 Transgenic Plants; The Ti Plasmid of Agrobacterium tumefaciens 605 Blocking Gene Expression with Antisense RNA 608 - // Technical Sidelight: DNA Tests and the Mystery of the Duchess Anastasia 596 // The Regulation of Gene Expression A Conversation with Mitzi I. Kuroda 613 // 23 REGULATION OF GENE EXPRESSION // IN PROKARYOTES AND THEIR VIRUSES 615 D’Hérelle’s Dream of Treating Dysentery
in Humans by Phage Therapy 615 Constitutive, Inducible, // and Repressible Gene Expression 617 Positive and Negative Control of Gene Expression 618 Operons: Coordinately Regulated Units of Gene Expression 620 The Lactose Operon in E. coli: Induction and Catabolite Repression 622 Induction 622 Catabolite Repression 625 The Tryptophan Operon in E. coli: // Repression and Attenuation 626 Repression 626 Attenuation 627 // Bacteriophage Lambda: Lysogeny or Lysis 630 Repression of Lambda Lytic Pathway Genes During Lysogeny 631 The Lambda Lytic Regulatory Cascade 634 The Lambda Switch: Lytic Development or Lysogeny 635 // Temporal Sequences of Gene Expression During Phage Infection 637 Translational Control of Gene Expression 638 Posttranslational Regulatory Mechanisms 639 // 24 REGULATION OF GENE EXPRESSION IN EUKARYOTES 644 // African Trypanosomes: A Wardrobe of Molecular Disguises 644 Spatial and Temporal Regulation of Eukaryotic Genes 645 // Spatial Regulation of Tubulin Genes in Plants 645 Temporal Regulation of Globin Genes in Animals 646 Ways of Regulating Eukaryotic Gene Expression 647 // Controlled Transcription of DNA 647 Alternate Splicing of RNA 648 Cytoplasmic Control of Messenger RNA Stability 649 Induction of Transcriptional Activity // by Environmental and Biological Factors 649 Temperature: The Heat-shock Genes 650 Light: The Ribulose 1,5-bisphosphate Carboxylase Genes in Plants 650 // Contents xvii // Signal Molecules: Genes That Respond to Hormones 651 // Molecular
Control of Transcription in Eukaryotes 653 // DNA Sequences Involved in the Control of Transcription 653 // Proteins Involved in the Control of Transcription: Transcription Factors 655 Gene Expression and Chromosome Organization 658 // Transcription in Lampbrush Chromosome Loops 658 Transcription in Polytene Chromosome Puffs 659 Molecular Organization // of Transcriptionally Active DNA 659 Euchromatin and Heterochromatin 660 Gene Silencing 661 DNA Methylation and Imprinting 665 Gene Amplification 666 Activation and Inactivation of Whole Chromosomes 668 // Inactivation ofX Chromosomes in Mammals 668 Hyperactivation of X Chromosomes in Drosophila 669 Hypoactivation of X Chromosomes in Caenorhabditis 670 Technical Sidelight: GAL4, a Transcription Factor That Regulates the Genes Involved in Galactose Metabolism in Yeast 656 // The Genetic Control of Biological Processes A Conversation with Eric Wieschaus 673 // 25 THE GENETIC CONTROL OF ANIMAL DEVELOPMENT 675 Insect Wings: Evidence for the Genetic Control of Development 675 // The Process of Development in Animals 676 Oogenesis and Fertilization 676 The Embryonic Cleavage Divisions and Blastula Formation 678 Gastrulation and Morphogenesis 678 Genetic Analysis of Development in Model Organisms 679 // Drosophila as a Model Organism 679 Caenorhabditis as a Model Organism 679 Genetic Analysis of Developmental Pathways 681 Sex Determination in Drosophila 682 Sex Determination in Caenorhabditis 685 The Use of Genetic Mosaics to Study Development
686 // X Chromosome Loss in Drosophila: Gynandromorphs 687 Somatic Recombination in Drosophila: // Twin Spots 687 // Molecular Analysis of Genes Involved in Development 689 // Maternal Gene Activity in Development 690 Maternal-Effect Geneš 690 Determination of the Dorsal-Ventral and Anterior-Posterior Axes in Drosophila Embryos 690 // Zygotic Gene Activity in Development 695 Body Segmentation 695 Specification of Cell Types 699 Organ Formation 702 // Genetic Analysis of Development in Vertebrates 703 Vertebrate Homologs of Invertebrate Genes 703 The Mouse: Insertional Mutagenesis, Transgenks, and Knockout Mutations 704 Technical Sidelight: The Development of Butterfly Wings: Insights from Drosophila Genetics 700 // 26 THE GENETIC CONTROL OF BEHAVIOR 710 // Twins and Personality 710 Genetic Analysis of Behavior in Experimental Animals 711 // Nest-Cleaning Behavior in Honeybees 711 Biological Rhythms in Drosophila and Mice 712 Sexual Preference in Drosophila 716 Nurturing Behavior in Mice 719 Chromosome Abnormalities and Insights into Human Behavior 720 Single-Gene Mutations and Human Behavior 721 Phenylketonuria 721 Lesch-Nyhan Syndrome 722 Huntington’s Disease 722 Complex Human Behaviors 723 Quantitative Human Genetics: // The Twin Correlation Method 723 Intelligence 724 Personality 725 // Human Genetics Sidelight: A Genetic Basis for Male Homosexuality? 718 // 27 THE GENETIC CONTROL OF THE VERTEBRATE IMMUNE SYSTEM 728 AIDS Emphasizes the Vital Role // of the Immune System 728
The Immune Response: An Overview 729 Components of the Mammalian Immune System 730 // Specialized Cells Mediate the Immune Response 730 Specialized Proteins Provide Immunological Specificity 732 Major Histocompatibility Antigens: // Distinguishing Self from Nonself 735 // xviii Contents // The Antibody-Mediated (Humoral) // Immune Response 736 The T Cell-Mediated (Cellular) // Immune Response 738 Immunological Memory 739 Genome Rearrangements During ? Lymphocyte Differentiation 740 // Lambda Light Chain Genes Assembled from Two Gene Segments 740 Kappa Light Chain Genes Assembled from Three Gene Segments 740 Heavy Chain Genes Assembled from Four Gene Segments 741 Signal Sequences Control // Somatic Recombination Events 742 Additional Diversity: Variable Joining Sites and Somatic Hypermutation 743 Antibody Class Switching 745 Assembly of T Cell Receptor Genes by Somatic Recombination 746 Regulation of Immunoglobin Gene Expression 746 // Allelic Exclusion: Only One Functional Rearrangement per Cell 746 Heavy Chain Gene Transcription: // A Tissue-Specific Enhancer 746 Technical Sidelight: Monoclonal Antibodies: // Powerful Probes for Detecting Proteins and Other Antigens 747 // 28 THE GENETIC BASIS OF CANCER 750 // A Common Killer 7SO Cancer; A Genetic Disease 751 // The Many Forms of Cancer 751 Cancer and the Cell Cycle 752 A Genetic Basis for Cancer 753 Oncogenes 753 // Tumor-Inducing Retroviruses and Viral Oncogenes 753 Cellular Homologs of Viral Oncogenes: // The Proto-Oncogenes
755 Mutant Cellular Oncogenes and Cancer 756 Chromosome Rearrangements and Cancer 758 Tumor Suppressor Genes 759 Inherited Cancers and // Knudson’s Two-Hit Hypothesis 759 Cellular Roles of Tumor Suppressor Proteins 761 // Genetic Pathways to Cancer 767 Human Genetics Sidelight: Cancer and Genetic Counseling 766 // The Genetics of the Evolutionary Process // A Conversation with Deborah and Brian Charlesworth 772 // 29 POPULATION AND EVOLUTIONARY GENETICS 774 // D’ou venons nousi Que sommes nous* // Ou allons nousi 774 The Emergence of Evolutionary Theory and Population Genetics 775 Darwin’s Theory of Evolution 775 Population Genetics 776 The Theory of Allele Frequencies 777 Estimating Allele Frequencies 777 Relating Genotype Frequencies to Allele Frequencies: The Hardy-Weinberg Principle 778 Applications of the Hardy-Weinberg Principle 778 Exceptions to the Hardy-Weinberg Principle 780 Using Allelic Frequencies in Genetic Counseling 781 Natural Selection 782 // Natural Selection at the Level of the Gene 782 Natural Selection at the Level of the Phenotype 785 Random Genetic Drift 786 // Random Changes in Allele Frequencies 786 The Effects of Population Size 787 Populations in Genetic Equilibrium 788 Balancing Selection 788 Mutation-Selection Balance 789 Mutation-Drift Balance 791 Genetic Variation in Natural Populations 793 Phenotypic Variation 793 Polymorphism of Chromosome Structure 794 Genetic Variation at the Molecular Level 794 Speciation 795 // Definition of Species 795
Modes of Speciation 796 Human Evolution 799 // Humans and the Great Apes 799 Human Evolution in the Fossil Record 799 DNA Sequence Variation and Human Origins 800 Technical Sidelight: Molecular Evolution and the Neutral Theory 790 A Conversation with James F Crow 805 // Epilogue: Genetics Yesterday, Today, and Tomorrow, by James F. Crow: A Personal View 807 Glossary 814 // Answers to Odd-Numbered Questions and Problems 832 Photo and Illustration Credits 850 Index 855

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