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har62485_TOC.qxd 12/17/02 12:24 PM Page x CONTENTS About the Authors Preface Acknowledgements CHAPTER 1 00 00 00 Genetics and Society Genetics: The Study of Biological Information The Biological Information Fundamental to Life Is Encoded in the DNA Molecule 000 Biological Function Emerges from Protein Molecules 000 Complex Systems Arise from DNA-Protein and Protein-Protein Interactions 000 All Living Things Are Closely Related Developing Guidelines for Genetic Screening 000 CHAPTER 3 Extensions to Mendel: Complexities in Relating Genotype to Phenotype 000 Extensions to Mendel for Single-Gene Inheritance Dominance Is Not Always Complete 000 000 000 A Gene May Have More Than Two Alleles The Modular Construction of Genomes Has Allowed the Relatively Rapid Evolution of Complexity 000 000 One Gene May Contribute to Several Visible Characteristics Genetic Techniques Permit the Dissection of Complexity Our Focus in on Human Genetics 000 000 000 000 How Human Genetics Is Leading Us Toward Predictive and Preventive Medicine 000 The New Scope of Human Genetics and the New Potential of Predictive and Preventive Medicine Intensify the Need to Confront Many Social Issues 000 000 A Comprehensive Example: Sickle-Cell Anemia Illustrates Many Extensions to Mendel’s Analysis of Single-Gene Inheritance Extensions to Mendel for Multifactorial Inheritance Two Genes Can Interact to Determine One Trait 000 000 000 Breeding Studies Help Decide How a Trait Is Inherited 000 The same genotype does not always produce the same phenotype 000 Even Continuous Variation Can Be Explained by Extensions to Mendelian Analysis 000 P A R T The Mouse’s Coat Color: A Comprehensive Example of Multiple Alleles and Multifactorial Traits 000 I Basic Principles: How Traits Are Transmitted 000 Genetics and Society 000 Disease Prevention Versus the Right to Privacy CHAPTER 4 The Chromosome Theory of Inheritance CHAPTER 2 Mendel’s Breakthrough: Patterns, Particles, and Principles of Heredity 000 Background: The Historical Puzzle of Inheritance A New Experimental Approach Evidence That Genes Reside in the Nucleus 000 Artificial Selection Was the First Applied Genetic Practice The Puzzle of Passing on Desirable Traits Chromosomes Contain the Genetic Material 000 Mitosis Ensures That Every Cell in an Organism Carries the Same Chromosomes 000 000 000 Genetic Analysis According to Mendel 000 Evidence That Genes Reside in Chromosomes 000 000 000 During Interphase, Cells Grow and Replicate Their Chromosomes 000 000 Monohybrid Crosses Reveal Units of Inheritance and the Law of Segregation 000 During Mitosis (M Phase), Sister Chromatids Separate and Are Apportioned to Different Daughter Nuclei 000 Mendel’s Results Reflect Basic Rules of Probability Regulatory Checkpoints Ensure Correct Chromosome Separation During Mitosis 000 000 Dihybrid Crosses Reveal the Law of Independent Assortment Why Mendel’s Work Was Unappreciated Before 1900 000 000 Meiosis Produces Haploid Germ Cells, the Gametes A Vertical Pattern of Inheritance Indicates a Rare Dominant Trait A Horizontal Pattern of Inheritance Indicates a Rare Recessive Trait 000 Fast Forward 000 Genes Encode Proteins Fast Forward 000 During Meiosis I, Homologous Chromosomes Pair, Exchange Parts, and Then Segregate from Each Other 000 During Meiosis II, Sister Chromatids Separate to Produce Haploid Gametes 000 A Summary of the Significant Events of Meiosis Meiosis Contributes to Genetic Diversity 000 Meiosis and Mitosis: A Comparison 000 The Direct Analysis of Human Genotype 000 000 Meiosis Consists of One Round of Chromosome Replication But Two Rounds of Nuclear Division 000 Mendelian Inheritance in Humans: A Comprehensive Example 000 000 000 000 Gametogenesis Requires Both Mitotic and Meiotic Divisions 000 x # 39689 Cust: MH/DBQ Au: Hartwell Pg. No. x Title: Genetics: From Genes to Genomes, 2nd ed. ISBN# 0-07246248-5 C/M/ Y/K 2Short / Short / Normal C O M M U N I C A T I O N S , L T D. har62485_TOC.qxd 12/17/02 12:24 PM Page xi xi Contents Egg Formation in Humans: Asymmetrical Meiotic Divisions Produce One Large Ovum 000 Spermatogenesis in Humans: Symmetrical Meiotic Divisions Produce Four Sperm 000 Validation of the Chromosome Theory 000 000 000 Some Genetic Information Is Accessible Even in Intact, DoubleStranded DNA Molecules 000 000 A Few Viruses Use RNA as Their Repository of Genetic Information How Gene Mutations Cause Errors in Mitosis Linkage, Recombination, and the Mapping of Genes on Chromosomes 000 Gene Linkage and Recombination 000 Some Genes on the Same Chromosome Assort Together More Often Than Not 000 Recombination Results When Crossing-Over During Meiosis Separates Linked Genes 000 Linkage and Recombination: A Summary 000 DNA Replication: Copying Genetic Information for Transmission to the Next Generation 000 000 CHAPTER 5 000 Mapping: Locating Genes Along a Chromosome Complementary Base Pairing Produces Semiconservative Replication: An Overview 000 The Molecular Mechanism of Replication: Doubling the Double Helix 000 The Mechanics of DNA Replication at the Chromosomal Level Three-Point Crosses: A Faster, More Accurate Way to Map Genes Recombination Reshuffles the Information Content of DNA 000 A Molecular Model of Crossing-Over Fast Forward 000 000 000 000 Restriction Enzymes Recognize Specific Base Sequences in DNA How Close Is the Correlation Between a Genetic Map and Physical Reality? 000 000 CHAPTER 7 Anatomy and Function of a Gene: Dissection Through Mutation 000 Multiple-Factor Crosses Help Establish Linkage Groups by Inference 000 Tetrad Analysis in Fungi: A Powerful Tool for Mapping and Understanding the Mechanisms of Recombination 000 Mitotic Recombination Can Produce Genetic Mosaics 000 Cells Must Ensure the Accuracy of Their Genetic Information—Before, During, and After Replication 000 During Recombination, DNA Molecules Break and Rejoin 000 Two-Point Crosses: Comparisons Help Establish Relative Gene Positions 000 Mutations: Primary Tools of Genetic Analysis 000 Mutations Are Heritable Changes in Base Sequences That Modify the Information Content of DNA 000 000 Spontaneous Mutations Influencing Phenotypes Occur at a Very Low Rate 000 000 Spontaneous Mutations Arise from Many Kinds of Random Events 000 Mutagens Induce Mutations Gene Mapping Leads to a Possible Cure for Cystic Fibrosis Genetics and Society 000 Much of DNA’s Sequence-Specific Information Is Accessible Only When the Double Helix Is Unwound 000 000 The Chromosome Theory Integrates Many Aspects of Gene Behavior 000 Fast Forward The Double Helix May Assume Alternative Forms DNA Stores Information in the Sequence of Its Bases Specific Traits Are Transmitted with Specific Chromosomes The Chi Square Test 000 The Double Helix Contains Two Antiparallel Chains That Associate by Complementary Base Pairing 000 DNA Structure Is the Foundation of Genetic Function The Chromosome Theory Correlates Mendel’s Laws with Chromosome Behavior During Meiosis 000 Fast Forward Nucleotides Are the Basic Building Blocks of DNA 000 Impact: Mutations Have Consequences for the Evolution of Species and the Survival of Organisms 000 000 Mitotic Recombination and Cancer Formation 000 000 What Mutations Tell Us About Gene Structure 000 000 Complementation Testing Reveals Whether Two Mutations Are in the Same or Different Genes 000 P A R T I A gene Is a Linear Sequence of Nucleotide Pairs That Can Mutate Independently and Recombine with Each Other 000 I What Genes Are and What They Do 000 A Gene Is a Discrete Linear Set of Nucleotide Pairs What Mutations Tell Us About Gene Function The One Gene, One Enzyme Hypothesis: A Gene Contains the Information for Producing a Specific Enzyme 000 CHAPTER 6 DNA: How the Molecule of Heredity Carries, Replicates, and Recombines Information 000 Experiments Designate DNA as the Genetic Material Bacterial Transformation Implicates DNA as the Substance of Genes Convincing Evidence That Genes Are DNA: The Molecule Carries the Information Required for the Replication of Bacterial Viruses 000 The Watson-Crick Model: DNA Is a Double Helix 000 Genes Specify the Identity and Order of Amino Acids in a Polypeptide Chain 000 000 Chemical Characterization Localizes DNA in the Chromosomes 000 000 How Genotype Correlates with Phenotype 000 000 000 Dominance Relations Between Alleles Depend on the Relation Between Protein Function and Phenotype 000 How Gene Mutations Affect Light-Receiving Proteins and Vision: A Comprehensive Example 000 The Cellular and Molecular Basis of Vision 000 How Mutations in the Rhodopsin Family Influence the Way We See # 39689 Cust: MH/DBQ Au: Hartwell Pg. No. xi Title: Genetics: From Genes to Genomes, 2nd ed. ISBN# 0-07246248-5 C/M/ Y/K 2Short / Short / Normal C O M M U N I C A T I O N S , L T D. 000 har62485_TOC.qxd 12/17/02 12:24 PM Page xii xii Contents Fast Forward 000 P Using Mutagenesis to Look at Biological Processes Genetics and Society 000 R T I I I 000 000 Amplified Trinucleotide Repeats May Have Medical Consequences 000 CHAPTER 9 Deconstructing the Genome: DNA at High Resolution 000 CHAPTER 8 Gene Expression: The Flow of Genetic Information from DNA via RNA to Protein 000 The Genetic Code: How Precise Groupings of the Four Nucleotides Specify 20 Amino Acids 000 A Gene’s Nucleotide Sequence Is Colinear with the Amino-Acid Sequence of the Encoded Polypeptide 000 Nonoverlapping Codons Are Set in a Reading Frame 000 Cracking the Code: Biochemical Manipulations Revealed Which Codons Represent Which Amino Acids 000 The Genetic Code: A Summary Different Restriction Enzymes Produce Different Numbers of Fragments from the Same Genome 000 Gel Electrophoresis Distinguishes DNA Fragments According to Size 000 000 Transcription: RNA Polymerase Synthesizes a Single-Stranded RNA Copy of a Gene 000 000 In Eukaryotes, RNA Processing After Transcription Produces a Mature mRNA 000 Translation: Base Pairing Between mRNA and tRNAs Directs Assembly of a Polypeptide on the Ribosome 000 Transfer RNAs Mediate the Translation of mRNA Codons to Amino Acids 000 Ribosomes Are the Sites of Polypeptide Synthesis 000 000 There Are Significant Differences in Gene Expression Between Prokaryotes and Eukaryotes 000 In Eukaryotes, the Nuclear Membrane Prevents the Coupling of Transcription and Translation 000 The Initiation of Translation Also Differs Between Prokaryotes and Eukaryotes 000 The Presence or Absence of Introns and RNA Processing To Purify Cloned DNA, You Separate Recombinant Plasmid Vector from Host DNA, and DNA Insert from Vector 000 Libraries Are Collections of Cloned Fragments 000 Expression Vectors Provide a Means for Producing Large Amounts of a Specific Polypeptide 000 Hybridization Is Used to Identify Similar DNA Sequences 000 Preparing the Library 000 Constructing the DNA Probes 000 000 Gel Electrophoresis Combined with Hybridization Provides a Tool for Mapping DNA Fragments 000 The Polymerase Chain Reaction Provides a Rapid Method for Isolating DNA Fragments 000 How PCR Achieves the Exponential Accumulation of Target DNA 000 PCR Products Can be Used Just Like Cloned Restriction Fragments 000 PCR Has Many Uses 000 000 DNA Sequence Analysis Comprehensive Example: A Computerized Analysis of Gene Expression in C. elegans 000 000 Mutations in a Gene’s Coding Sequence Can Alter the Gene Product 000 Mutations in a Gene Outside the Coding Sequence Can Also Alter Gene Expression 000 Mutations in Genes Encoding the Molecules That Implement Expression May Affect Transcription, mRNA Splicing, or Translation 000 Genetics and Society 000 Cloning Step 2: Host Cells Take up and Amplify Vector-Insert Recombinants 000 Screening the Library Processing After Translation Can Change a Polypeptide’s Structure 000 How Mutations Affect Gene Expression 000 Restriction Maps Provide a Rough Roadmap of Virus Genomes and Other Purified DNA Fragments 000 Cloning Step 1: Ligation of Fragments to Cloning Vectors Creates Recombinant DNA Molecules 000 The Genetic Code Is Almost, but Not Quite, Universal The Mechanism of Translation 000 Different Restriction Enzymes Produce Fragments of Different Lengths 000 Cloning Fragments of DNA 000 Using Genetics to Verify the Code Fragmenting Complex Genomes into Bite-Size Pieces for Analysis 000 Restriction Enzymes Fragment the Genome at Specific Sites In the Genetic Code, a Triplet Codon Represents Each Amino Acid 000 Details of the Process A Genomes 000 000 General Principles of the Procedure Sequencing Long Regions of DNA Understanding the Genes for Hemoglobin: A Comprehensive Example 000 The Genes Encoding Hemoglobin Occur in Two Clusters on Two Separate Chromosomes 000 A Variety of Mutations Account for the Diverse Symptoms of GlobinRelated Diseases 000 The - and -Globin Loci House Multiple Genes That Evolved from One Ancestral Gene 000 Genetics and Society HIV and Reverse Transcription: An Unusual DNA Polymerase Helps Give the AIDS Virus an Evolutionary Edge 000 000 000 000 Serendipity in Science: The Discovery of Restriction Enzymes # 39689 Cust: MH/DBQ Au: Hartwell Pg. No. xii Title: Genetics: From Genes to Genomes, 2nd ed. ISBN# 0-07246248-5 C/M/ Y/K 2Short / Short / Normal C O M M U N I C A T I O N S , L T D. 000 har62485_TOC.qxd 12/17/02 12:24 PM Page xiii Contents CHAPTER 10 Reconstructing the Genome Through Genetic and Molecular Analysis 000 CHAPTER 11 The Direct Detection of Genotype Distinguishes Individual Genomes 000 Analyses of Genomes DNA Variation Is Multifaceted and Widespread 000 The Genomes of Living Organisms Vary Enormously in Size 000 Genomicists Look at Two Basic Features of Genomes: Sequence and Polymorphisms 000 Four Relatively Simple Techniques Make Genome Characterization Possible 000 Large-Scale Maps Serve as Guides to Whole Genomes 000 High-Density Linkage Maps: Computerized Analyses of Transmission Data Position Unlimited Numbers of Markers in Relation to Each Other 000 The Making of Large-Scale Linkage Maps 000 The Integration of Linkage, Physical, and Sequence Maps 000 000 There Are Three Approaches to the Direct Detection of SNPs How to Detect Alleles That Change the Length of a Locus Major Insights from the Human and Model Organism Genome Sequences 000 000 The Genome Contains Distinct Types of Gene Organization 000 Evolution May Occur by the Lateral Transfer of Genes from One Organism to Another 000 Males Appear to Have More Than a Twofold Increased Rate of Mutation in Meiosis over Females 000 How Geneticists Move from Complex Traits to Sets of Contributing Loci 000 Genetics and Society Genetics and Society P 000 000 Global Proteomic Strategies and High-Throughput Platforms 000 Uses of Genomic and Proteomic High-Throughput Platforms 000 R T I V 000 The Eukaryotic Chromosome: An Organelle for Packaging and Managing DNA 000 The Components of Eukaryotic Chromosomes: DNA, Histones, and Nonhistone Proteins 000 Each Chromosome Packages a Single Long Molecule of DNA 000 The Protein Components of Eukaryotic Chromosomes: Histones and Nonhistone Proteins 000 Chromosome Structure: Variable DNA-Protein Interactions Create Reversible Levels of Compaction 000 000 Predictive/Preventive Medicine 000 Predictive/Preventive Medicine Raises Challenging Social, Ethical, and Legal Issues for Which There Are No Simple Solutions 000 The Patentability of DNA A How Genes Travel CHAPTER 12 High-Throughput Genomic and Proteomic Platforms Permit the Global Analysis of Gene Products 000 Genetics and Society 000 Using Human Pedigrees and LOD Scores to Calculate the Probability That Two Loci Are Linked 000 The Sequences of the Human and Model Organism Genomes Reaffirm That All Living Organisms Evolved from a Common Ancestor 000 In the Future, Other Features of Chromosomes Will Become Increasingly Important 000 000 000 Social and Ethical Issues Surrounding Preimplantation Embryo Diagnosis 000 The Different Human Races Appear to Have Very Few Uniquely Distinguishing Genes 000 Systems Biology 000 How the Causes of Complex Inheritance Patterns Confound Linkage Mapping and Thus Positional Cloning 000 Haplotypes Are Sets of Closely Linked Alleles Combinatorial Strategies May Amplify Genetic Information and Generate Diversity 000 Global Genomic Strategies and High-Throughput Platforms 000 Haplotype Association Studies for High-Resolution Mapping in Humans 000 000 Repeat Sequences Constitute More Than 50% of the Human Genome 000 High-Throughput Instruments 000 000 Comprehensive Example: Positional Cloning of the Cystic Fibrosis Gene Leads to a Potential Therapy 000 Genetic Dissection of Complex Traits The Human Genome Project Has Changed the Practice of Biology, Genetics, and Genomics 000 Genes Encode Either Noncoding RNAs or Proteins Detecting DNA Genotypes of Different Types of Polymorphisms 000 In Positional Cloning, Linkage Analysis with DNA Markers Helps Identify Disease Genes 000 A Sequence Map Is the Highest-Resolution Genomic Map There Are 40,000–60,000 Human Genes Geneticists Categorize DNA Polymorphisms in Four Different Classes 000 In Rare Cases, It Is Possible to Move from a Disease Phenotype to the Causative Gene Without Linkage Analysis 000 Long-Range Physical Maps: Karyotypes and Genomic Libraries Provide the Basis for Positioning Markers on Chromosomes 000 Finding Genes in a Sequenced Genome 000 Members of the Same Species Show Enormous Sequence Variation in Their Genomes 000 Positional Cloning: from DNA Markers to Gene Clones 000 xiii 000 000 The Nucleosome: The Fundamental Unit of Chromosomal Packaging Arises from DNA’s Association with Histones 000 Models of Higher-Level Packaging Seek to Explain the Extreme Compaction of Chromosomes at Mitosis 000 A Closer Look at Karyotypes: Fully Compacted Metaphase Chromosomes Have Unique, Reproducible Banding Patterns That Identify Them 000 # 39689 Cust: MH/DBQ Au: Hartwell Pg. No. xiii Title: Genetics: From Genes to Genomes, 2nd ed. ISBN# 0-07246248-5 C/M/ Y/K 2Short / Short / Normal C O M M U N I C A T I O N S , L T D. har62485_TOC.qxd 12/17/02 12:24 PM Page xiv xiv Contents Specialized Chromosomal Elements Ensure Accurate Replication and Segregation of Chromosomes 000 The Accurate Duplication of Chromosome Structure Depends on Origins of Replication and Telomeres 000 How Bacteria Move to Achieve Chemotaxis Controlled Decompaction Precedes Gene Expression The Future of Bacterial Genetics 000 000 000 Rearrangements of DNA Sequences Within Chromosomes Duplications Add Material to the Genome 000 000 000 Translocations Attach Part of One Chromosome to Another Chromosome 000 Transposable Genetic Elements Move from Place to Place in the Genome 000 Rearrangements and Evolution: A Speculative Comprehensive Example 000 Changes in Chromosome Number 000 CHAPTER 15 The Chromosomes of Organelles Outside the Nucleus Exhibit Non-Mendelian Patterns of Inheritance 000 The Structure and Function of Mitochrondrial and Chloroplast Genomes 000 000 Inversions Reorganize the DNA Sequence of a Chromosome 000 000 How Bacteria Cause Disease Chromosomal Rearrangements and Changes in Chromosome Number Reshape Eukaryotic Genomes 000 000 The Loss or Gain of One or More Chromosomes Results in Aneuploidy 000 Some Euploid Species Contain Complete but Nondiploid Sets of Chromosomes 000 A Glimpse of the Future: Emergent Technologies in the Analysis of Chromosomal Rearrangments and Changes in Chromosome Number 000 Mitochondria and Chloroplasts Are Organelles of Energy Conversion That Carry Their Own DNA 000 The Genomes of Mitochondria The Genomes of Chloroplasts 000 000 Mitochondria and Chloroplast Functions Require Cooperation Between the Organelle and Nuclear Genomes 000 Origin and Evolution of Organelle Genomes: The Molecular Evidence 000 Genetic Studies of Organelle Genomes Clarify Key Elements of non-Mendelian Inheritance 000 In Most Species, Progeny Inherit Organelle DNA from Only One— Usually the Maternal—Parent 000 Some Organisms Exhibit Biparental Inheritance Development of the Immune System Depends on Programmed DNA Rearranngements 000 Individuals with Certain Rare Diseases of the Nervous System Are Heteroplasmic for Wild-Type and Mutant mtDNAs 000 Mitochondrial Inheritance in Identical Twins CHAPTER 14 Mitochondrial Mutations and Aging The Prokaryotic Chromosome: Genetic Analysis in Bacteria 000 A General Overview of Prokaryotes The Immense Diversity of Bacteria 000 Fast Forward 000 000 Genetics and Society 000 000 000 Mitochondrial DNA Tests Replace HLA Typing as Evidence of Kinship in Argentine Courts 000 000 P Plasmids: Smaller Circles of DNA That Do Not Carry Essential Genes 000 Gene Transfer in Bacteria 000 000 Mitochondrial DNA Sequences Shed Light on Human Evolution The Power of Bacterial Genetics Is the Potential for Studying Rare Events 000 One Circular Chromosome 000 Summary of the Genetic Principles of Non-Mendelian Inheritance 000 Comprehensive Example: How Mutations in mtDNA Affect Human Health 000 000 The Bacterial Genome 000 Genomic Information Has Forced Scientists to Reevaluate Their Notions of Bacterial Evolutions 000 Genetics and Society CHAPTER 13 Fast Forward Comparative Genome Analysis Can Help Dissect the Genetic Basis of Bacterial Behavior 000 Challenges for the Postgenomic Era Unusual Chromosome Structures Clarify the Correlation Between Chromosome Packaging and Gene Function 000 Deletions Remove Material from the Genome 000 000 The Fruits of Genomic Analysis May Help Protect Human Health By Influencing Gene Expression, Chromatin Packaging Affects Tissue Differentiation 000 Extreme Condensation Silences Expression 000 Many Bacterial Mutants Cannot Carry out Chemotaxis The Segregation of Condensed Chromosomes Depends on Centromeres 000 How Chromosomal Packaging Influences Gene Activity Comprehensive Example: Genetic Dissection Helps Explain How Bacteria Move 000 A R T V How Genes Are Regulated 000 000 Transformation: Fragments of Donor DNA Enter the Recipient and Alter Its Genotype 000 Conjugation: Donor Cells Carrying Specialized Plasmids Establish Contact with and Transfer DNA to Recipients 000 Transduction: Gene Transfer via Bacteriophage Bacterial Genetic Analysis Today 000 000 CHAPTER 16 Gene Regulation in Prokaryotes 000 An Overview of Prokaryotic Gene Regulation 000 RNA Polymerase Is the Key Enzyme for Transcription # 39689 Cust: MH/DBQ Au: Hartwell Pg. No. xiv Title: Genetics: From Genes to Genomes, 2nd ed. ISBN# 0-07246248-5 C/M/ Y/K 2Short / Short / Normal 000 C O M M U N I C A T I O N S , L T D. har62485_TOC.qxd 12/17/02 12:24 PM Page xv xv Contents Translation in Prokaryotes Starts Before Transcription Ends Regulation of Gene Expression Can Occur at Many Steps The Regulation of Gene Transcription 000 Protein Modifications After Translation Provide a Final Level of Control over Gene Function 000 000 Sex Determination in Drosophila: A Comprehensive Example of Gene Regulation 000 000 The Utilization of Lactose by E. coli: A Model System for Studying Gene Regulation 000 A. The X:A Ratio Regulates Expression of the Sex Lethal (Sxl) Gene 000 Experiments Analyzing the Behavior of Lactose-Utilization Mutants Reveal the Coordinate Repression and Induction of Three Genes 000 The Operon Theory Sxl Triggers a Cascade of Splicing 000 A Positive Control Increases Transcription of lacZ, lacY, and lacA 000 Summary of how DNA-Binding Proteins Control the Initiation of Transcription at the Lactose and Other Operons 000 Molecular Studies Help Fill in the Details of Control Mechanisms 000 The Attenuation of Gene Expression: Fine-Tuning of the trp Operon Through the Termination of Transcription 000 The Presence of Tryptophan Activates a Repressor of the trp Operon 000 Global Regulatory Mechanisms Coordinate the Expression of Different Sets of Genes 000 An Alternative Sigma () Factor Mediates E. coli’s Global Response to Heat Shock 000 Microarrays Provide a New Tool for Studying Genes Regulated as Part of a Global Response 000 A Comprehensive Example: The Regulation of Virulence Genes in V. cholera 000 Three Regulatory Proteins—ToxR, ToxS, and ToxT—Turn on the Genes for Virulence 000 Genetics and Society 000 Summary: A Complex Network of Molecular Interactions Regulates the Determination of Somatic Sexual Characteristics in Drosophila 000 Genetics and Society 000 CHAPTER 18 Cell-Cycle Regulation and the Genetics of Cancer 000 The Normal Control of Cell Division 000 Cyclin-Dependent Kinases Collaborate with Cyclins to Ensure the Proper Timing and Sequence of Cell-Cycle Events 000 Cell-Cycle Checkpoints Integrate Repair of Chromosomal Damage with Events of the Cell Cycle 000 A Cascade of External and Internal Molecules Tells Cells Whether or Not to Initiate Division 000 Cancer Arises When Controls over Cell Division No Longer Function Properly 000 The Cancer Phenotype Results from the Accumulation of Multiple Mutations in the Clonal Progeny of a Cell 000 000 Nitrogen Fixation Depends on Many Levels of Gene Regulation 000 CHAPTER 17 Gene Regulation in Eukaryotes The Tra and Tra-2 Proteins Also Help Regulate Expression of the Fruitless Gene 000 A Promising Medical Tool: Synthetic Oligonucleotides That Selectively Reduce the Expression of Specific Gene Products 000 The Termination of Transcription Fine-Tunes Regulation of the trp Operon 000 A Model of Virulence Regulation Leaves Unanswered Questions 000 The Dsx-F and Dsx-M Proteins Are Transcription Factors That Determine Somatic Sexual Characteristics 000 Summary: The Accumulation of Oncogenic and Tumor-Suppressor Mutations Produces Cancer Cells with Grossly Altered Genomes 000 000 The Use of Genetics to Study Gene Regulation 000 The Analysis of Regulatory Components Focuses on Mutations That Affect a Gene’s Function but Do Not Affect the Amino Acids in the Gene’s Product 000 Most Gene Regulation Occurs at the Initiation of Transcription 000 000 000 A Large Number of Genes in Various Combinations Produce GBMs 000 000 Genetic Testing Has Some Use in Predicting and Treating Cancer A Locus Control Region Is a cis-Acting Regulatory Sequence That Operates Sequentially on a Cluster of Related Genes 000 Complex Regulatory Regions Allow an Organism to Fine-Tune Gene Expression 000 000 Regulation After Transcription Influences RNA Production, Protein Synthesis, and Protein Stability 000 CHAPTER 19 Using Genetics to Study Development Why These Model Organisms? . . . Yet All Species Are Unique RNA Stability Provides a Mechanism for Controlling the Amount of Gene Product Synthesized 000 mRNA Editing Can Affect the Biological Properties of a Gene’s Product 000 000 000 000 000 Genetics Simplifies the Study of Development 000 The Genetic Dissection of Development Depends on a Comprehensive Set of Mutants 000 Mutant Screens Help Identify the Components of Development 000 000 000 Model Organisms: Prototypes for Developmental Genetics All Living Forms Are Related. . . 000 Noncoding Sequences in mRNA Can Help Modulate Translation Cellular and Clinical Background Genetics and Society trans-Acting Proteins Control Transcription from Class II Promoters 000 Chromatin Structure Plays a Role in Eukaryotic Gene Regulation Comprehensive Example: The Genetics of Brain Cancer Knowledge of the Genetics of Brain Cancer May Lead to More Selective Therapies 000 In Eukaryotes, Three RNA Polymerases Transcribe Different Sets of Genes 000 RNA Splicing Helps Regulate Gene Expression The Mutations That Lead to Cancer Create Dominant Oncogenic Alleles or Recessive Mutant Tumor-Suppressor Alleles 000 Analyzing How Genes Work Together in Developmental Pathways # 39689 Cust: MH/DBQ Au: Hartwell Pg. No. xv Title: Genetics: From Genes to Genomes, 2nd ed. ISBN# 0-07246248-5 C/M/ Y/K 2Short / Short / Normal C O M M U N I C A T I O N S , L T D. 000 000 har62485_TOC.qxd 12/17/02 12:24 PM Page xvi xvi Contents How Genes Help Control Development: A Mechanistic Framework 000 The Immunoglobulin Gene Superfamily: A Comprehensive Example of Molecular Evolution 000 Development Requires Progressive Changes in Gene Expression Development Exploits Asymmetries 000 000 Evolution of the Immunoglobulin Homology Unit 000 Evolution of the Immunoglobulin Gene Superfamily Cell-to-Cell Communication Is Essential for Proper Development Genes Explain Much, but Not Everything, About Development 000 000 000 Immune-Cell Receptors Provide the Backbone of the Immune Response 000 Evolution of the Vertebrate Immune Response: A Possible Scenario 000 P A R T V How Genes Change Comparisons of the Sequences of T-Cell Receptor Gene Families Provide a Snapshot of Evolution 000 I 000 REFERENCE A Saccharomyces cerevisiae: A Genetic Portrait of Yeast 000 CHAPTER 20 An Overview of Yeast in the Laboratory The Genetic Analysis of Populations and How They Evolve 000 The Nuclear Genome of Yeast The Hardy-Weinberg Law: A Model for Understanding Allele, Genotype, and Phenotype Frequencies for a Single-Gene Trait in a Genetically Stable Population 000 The Hardy-Weinberg Law Correlates Allele and Genotype Frequencies Through a Binomial Equation 000 Evolutionary Equilibrium: A Balance Between Mutation to a New Allele and Selection Against That Allele 000 Comprehensive Example: How Human Activity Affects the Evolution of Human Pathogens and Crop Pests 000 000 000 Heritability Is the Proportion of Total Phenotype Variance Attributable to Genetic Variance 000 How to Measure Heritability 000 000 CHAPTER 21 Arabidopsis thaliana: Genetic Portrait of a Model Plant 000 Genome Structure and Organization 000 DNA Alterations Form the Basis of Genomic Evolution 000 An Increase in Genome Size Generally Correlates with the Evolution of Complexity 000 Molecular Archeology Based on an Understanding of Gene Diversification and Selection 000 The Organization of Genomes Mechanisms Behind the Expansion from Genes to Multigene Families to Gene Superfamilies 000 Repetitive “Nonfunctional” DNA Families Constitute Nearly One-Half of the Genome 000 Genomic Stutters—the Simple Sequence Repeats Known as Microsatellites, Minisatellites, and Macrosatellites—Dot the Mammalian Genome 000 Repeat Sequences in Centromeres and Telomeres 000 000 000 000 000 000 Life Cycle: From Fertilization to Flowering to Senescence Techniques of Mutational Analysis 000 000 Mutagenesis by Chemical and Irradiation Procedures Produces Different Ratios of Various Mutations 000 Arabidopsis Researchers Use Two Types of Insertional Mutagenesis: Transformation by T-DNA and Transposon Tagging 000 From Gene to Phenotype: Analyzing Mutations to Identify Gene Function 000 The Genetic Analysis of Development in Arabidopsis The Genetic Analysis of Embryogenesis 000 000 000 Little Repetitive DNA and a Tight Arrangement of Genes Anatomy: The Basic Body Plan The Evolution of Living Organisms: Inferences from the Fossil Record 000 Unique Nongene Sequences REFERENCE B Anatomy and Life Cycle 000 000 Descent from a Single Ancestor: Speculations on How the First Cell Arose 000 The Evolution of Genomes Cells Respond to the Binding of Pheromone Through a Signal Transduction System 000 Summary Evolution at the Molecular Level 000 Mating: Cell-to-Cell Communication Through Pheromones Triggers the Conversion of Haploid a and Cells to a/ Diploids 000 Comparing Genetic and Physical Maps The Heritability of a Trait Determines Its Potential for Evolution The Origin of Life on Earth Cell Differentiation in Yeast: Mechanisms for Determining Cell Type 000 Mating Type Switching Natural Selection Acts on Differences in Fitness to Alter Allele Frequencies 000 Genes Versus the Environment 000 000 The MAT Locus Controls Expression of the Genes That Determine Cell Type 000 Beyond Hardy-Weinberg: Measuring How Mutation and Selection Cause Changes in Allele Frequencies 000 Analyzing the Quantitative Variation of Multifactorial Traits Basic Tools of the Yeast Geneticist The Yeast Life Cycle 000 000 000 000 The Genetic Analysis of Hormonal Control Systems 000 The Genetic Analysis of Photomorphogenesis—The Regulation of Growth and Development in Response to Lighting Cues 000 The Genetic Analysis of Flowering: A Comprehensive Example 000 How Genes Determine the Body Plan of a Flower 000 Earlier-Acting Genes Specify the Identity of the Floral Meristem Some Genes Control the Timing of FM Formation and Flowering 000 # 39689 Cust: MH/DBQ Au: Hartwell Pg. No. xvi Title: Genetics: From Genes to Genomes, 2nd ed. ISBN# 0-07246248-5 C/M/ Y/K 2Short / Short / Normal C O M M U N I C A T I O N S , L T D. 000 har62485_TOC.qxd 12/17/02 12:24 PM Page xvii Contents xvii REFERENCE C Caenorhabditis elegans: Genetic Portrait of a Simple Multicellular Organism 000 Early Development of the Basic Body Plan An Overview of C. elegans as an Experimental Organism Specification of Segment Number Through the Activation of Zygotic Genes in Successively More Sharply Defined Regions of the Embryo 000 The Nuclear Genome of C. elegans 000 000 Life Cycle, Development, and Anatomy 000 The Use of Genetic Analysis and Recombinant DNA Technology to Study Development 000 Programmed Cell Death Each Segment Establishes Its Own Unique Identity Through the Activation of Homeotic Genes 000 REFERENCE E Mus musculus: Genetic Portrait of the House Mouse 000 The Genetic Dissection of Developmental Processes in C. elegans 000 Specification of Early Embryonic Blastomeres 000 Specification of Segment Number: Maternal Genes Interact to Produce Gradients of Morphogen Gradients 000 000 An Overview of Mus musculus in the Laboratory 000 Control of Timing During Larval Development The Mouse Genome 000 The Mammalian Life Cycle Using Genetics to Probe the Development of the Hermaphrodite Vulva: A Comprehensive Example 000 Mutant Screens Identify Genes Involved in Vulva Formation 000 Organizing the Genes Contributing to Vulva Formation into a Signaling Pathway 000 000 000 000 Two Powerful Transgenic Techniques for Analyzing the Mouse Genome 000 How Biologists Use Transgenic Tools to Study Mice and Create a Mouse Model for Human Disease 000 Using Transgenic Technology to Determine Gene Function REFERENCE D Drosophila melanogaster: Genetic Portrait of the Fruit Fly 000 Structure and Organization of the Drosophila Genome The Chromosomes of Drosophila The Drosophila Genome Life Cycle 000 Using Transgenic Technology to Link Mutant Phenotypes to Specific Transcription Units 000 Using Targeted Mutagenesis to Create a Mouse Model for Human Disease 000 000 000 The Hox Genes: A Comprehensive Example 000 Techniques of Genetic Analysis In Drosophila, Crossing-Over Occurs Only in Females 000 000 P-Element Transposons the Critical Tools in Drosophila Molecular Genetics 000 The Production of Genetic Mosaics Ectopic Expression 000 000 The Drosophila Genome Project 000 How Scientists Determine the Function of a Gene in the Absence of Previously Characterized Mutations 000 000 Balancer Chromosomes Help Preserve Linkage 000 Using Transgenic Technology to Characterize Regulatory Regions 000 000 The Genetic Analysis of Body Plan Development in Drosophila: A Comprehensive Example 000 Validating the Hypothesis That Expression of the 5′ Gene in a Hox Cluster Is Epistatic to Expression of the More 3′ Genes 000 Transgenic Studies Lead to an Understanding of the Developmental Role of Hox and Other Homeotic Genes 000 Guidelines for Gene Nomenclature Brief Answer Section Glossary Index # 39689 Cust: MH/DBQ Au: Hartwell Pg. No. xvii Title: Genetics: From Genes to Genomes, 2nd ed. ISBN# 0-07246248-5 000 000 C/M/ Y/K 2Short / Short / Normal C O M M U N I C A T I O N S , L T D.