TY - BOOK AU - Klug, William S. AU - Cummings, Michael R. AU - Spencer, Charlotte A AU - Palladino, Michael TI - Concepts of Genetics SN - 9780321524041 U1 - 576.5 PY - 2006/// CY - San Fracisco PB - Pearson Education KW - Genetics N1 - 1 INTRODUCTION TO GENETICS 1.1 Genetics Progressed from Mendel to DNA in Less Than a Century Mendel¿s Work on Transmission of Traits The Chromosome Theory of Inheritance: Uniting Mendel and Meiosis Genetic Variation The Search for the Chemical Nature of Genes: DNA or Protein? 1.2 Discovery of the Double Helix Launched the Era of Molecular Genetics The Structure of DNA and RNA Gene Expression: From DNA to Phenotype Proteins and Biological Function Linking Genotype to Phenotype: Sickle-Cell Anemia 1.3 Development of Recombinant DNA Technology Began the Era of Cloning 1.4 The Impact of Biotechnology Is Continually Expanding Plants, Animals, and the Food Supply Who Owns Transgenic Organisms? Biotechnology in Genetics and Medicine 1.5 Genomics, Proteomics, and Bioinformatics Are New and Expanding Fields 1.6 Genetic Studies Rely on the Use of Model Organisms The Modern Set of Genetic Model Organisms Model Organisms and Human Diseases 1.7 We Live in the ¿Age of Genetics¿ The Nobel Prize and Genetics Genetics and Society 2 MITOSIS AND MEIOSIS 2.1 Cell Structure Is Closely Tied to Genetic Function 2.2 Chromosomes Exist in Homologous Pairs in Diploid Organisms 2.3 Mitosis Partitions Chromosomes into Dividing Cells Interphase and the Cell Cycle Prophase Prometaphase and Metaphase Anaphase Telophase Cell Cycle Regulation and Checkpoints 2.4 Meiosis Reduces the Chromosome Number from Diploid to Haploid in Germ Cells and Spores An Overview of Meiosis The First Meiotic Division: Prophase I Metaphase, Anaphase, and Telophase I The Second Meiotic Division 2.5 The Development of Gametes Varies in Spermatogenesis Compared to Oogenesis 2.6 Meiosis Is Critical to the Successful Sexual Reproduction of All Diploid Organisms 2.7 Electron Microscopy Has Revealed the Physical Structure of Mitotic and Meiotic Chromosomes The Synaptonemal Complex 3 MENDELIAN GENETICS 3.1 Mendel Used a Model Experimental Approach to Study Patterns of Inheritance 3.2 The Monohybrid Cross Reveals How One Trait Is Transmitted from Generation to Generation Mendel¿s First Three Postulates Modern Genetic Terminology Mendel¿s Analytical Approach Punnett Squares The Testcross: One Character 3.3 Mendel¿s Dihybrid Cross Generated a Unique F2 Ratio Mendel¿s Fourth Postulate: Independent Assortment The Testcross: Two Characters 3.4 The Trihybrid Cross Demonstrates that Mendel¿s Principles Apply to Inheritance of Multiple Traits The Forked-Line Method or Branch Diagram 3.5 Mendel¿s Work Was Rediscovered in the Early Twentieth Century 3.6 The Correlation of Mendel¿s Postulates with the Behavior of Chromosomes Formed the Foundation of Modern Transmission Genetics The Chromosomal Theory of Inheritance Unit Factors, Genes, and Homologous Chromosomes 3.7 Independent Assortment Leads to Extensive Genetic Variation 3.8 Laws of Probability Help to Explain Genetic Events Conditional Probability The Binomial Theorem 3.9 Chi-Square Analysis Evaluates the Influence of Chance on Genetic Data Chi-Square Calculations and the Null Hypothesis Interpreting Probability Values 3.10 Pedigrees Reveal Patterns of Inheritance of Human Traits Pedigree Conventions Pedigree Analysis 4 EXTENSIONS OF MENDELIAN GENETICS 4.1 Alleles Alter Phenotypes in Different Ways 4.2 Geneticists Use a Variety of Symbols for Alleles 4.3 Neither Allele Is Dominant in Incomplete, or Partial, Dominance 4.4 In Codominance, the Influence of Both Alleles in a Heterozygote Is Clearly Evident 4.5 Multiple Alleles of a Gene May Exist in a Population The ABO Blood Groups The A and B Antigens The Bombay Phenotype The white Locus in Drosophila 4.6 Lethal Alleles Represent Essential Genes Recessive Lethal Mutations Dominant Lethal Mutations 4.7 Combinations of Two Gene Pairs with Two Modes of Inheritance Modify the 9:3:3:1 Ratio 4.8 Phenotypes Are Often Affected by More Than One Gene Epistasis Novel Phenotypes Other Modified Dihybrid Ratios 4.9 Complementation Analysis Can Determine if Two Mutations Causing a Similar Phenotype Are Alleles 4.10 Expression of a Single Gene May Have Multiple Effects 4.11 X-Linkage Describes Genes on the X Chromosome X-Linkage in Drosophila X-Linkage in Humans 4.12 In Sex-Limited and Sex-Influenced Inheritance, an Individual¿s Sex Influences the Phenotype 4.13 Genetic Background and the Environment May Alter Phenotypic Expression Penetrance and Expressivity Genetic Background: Suppression and Position Effects Temperature Effects ¿ An Introduction to Conditional Mutations Nutritional Effects Onset of Genetic Expression Genetic Anticipation Genomic (Parental) Imprinting 5 CHROMOSOME MAPPING IN EUKARYOTES 5.1 Genes Linked on the Same Chromosome Segregate Together The Linkage Ratio 5.2 Crossing Over Serves as the Basis for Determining the Distance between Genes in Chromosome Mapping Morgan and Crossing Over Sturtevant and Mapping Single Crossovers 5.3 Determining the Gene Sequence during Mapping Requires the Analysis of Multiple Crossovers Multiple Exchanges Three-Point Mapping in Drosophila Determining the Gene Sequence A Mapping Problem in Maize 5.4 Interference Affects the Recovery of Multiple Exchanges 5.5 As the Distance between Two Genes Increases, the Results of Mapping Experiments Become Less Accurate 5.6 Drosophila Genes Have Been Extensively Mapped 5.7 Lod Score Analysis and Somatic Cell Hybridization Were Historically Important in Creating Human Chromosome Maps 5.8 Chromosome Mapping Is Now Possible Using Molecular Analysis of DNA Gene Mapping Using Annotated Computer Databases 5.9 Crossing Over Involves a Physical Exchange between Chromatids 5.10 Recombination Also Occurs between Mitotic Chromosomes 5.11 Exchanges Occur between Sister Chromatids Too 5.12 Linkage and Mapping Studies Can Be Performed in Haploid Organisms Gene-to-Centromere Mapping Ordered versus Unordered Tetrad Analysis Linkage and Mapping 5.13 Did Mendel Encounter Linkage? 6 GENETIC ANALYSIS AND MAPPING IN BACTERIA AND BACTERIOPHAGES 6.1 Bacteria Mutate Spontaneously and Grow at an Exponential Rate 6.2 Conjugation Is One Means of Genetic Recombination in Bacteria and Bacteria Hfr Bacteria and Chromosome Mapping Recombination in Matings: A Reexamination The State and Merozygotes 6.3 Rec Proteins Are Essential to Bacterial Recombination 6.4 The F Factors Is an Example of a Plasmid 6.5 Transformation Is Another Process Leading to Genetic Recombination in Bacteria The Transformation Process Transformation and Linked Genes 6.6 Bacteriophages Are Bacterial Viruses Phage T4: Structure and Life Cycle The Plaque Assay Lysogeny 6.7 Transduction Is Virus-Mediated Bacterial DNA Transfer The Lederberg¿Zinder Experiment The Nature of Transduction Transduction and Mapping 6.8 Bacteriophages Undergo Intergenic Recombination Bacteriophage Mutations Mapping in Bacteriophages 6.9 Intragenic Recombination Occurs in Phage T4 The rII Locus of Phage T4 Complementation by rII Mutations Recombinational Analysis Deletion Testing of the rII Locus The rII Gene Map 7 SEX DETERMINATION AND SEX CHROMOSOMES 7.1 Life Cycles Depend on Sexual Differentiation Chlamydomonas Zea mays Caenorhabditis elegans 7.2 X and Y Chromosomes Were First Linked to Sex Determination Early in the 20th Century 7.3 The Y Chromosome Determines Maleness in Humans Klinefelter and Turner Syndromes 47,XXX Syndrome 47,XYY Condition Sexual Differentiation in Humans The Y Chromosome and Male Development 7.4 The Ratio of Males to Females in Humans Is Not 1.0 7.5 Dosage Compensation Prevents Expression of X-Linked Genes in Humans and Other Mammals Barr Bodies The Lyon Hypothesis The Mechanisms of Inactivation 7.6 The Ratio of X Chromosomes to Sets of Autosomes Determines Sex in Drosophila Dosage Compensation in Drosophila Drosophila Mosaics 7.7 Temperature Variation Controls Sex Determination in Reptiles 8 CHROMOSOME MUTATIONS: VARIATION IN CHROMOSOME NUMBER AND ARRANGEMENT 8.1 Variation in the Number of Chromosomes Results from Nondisjunction 8.2 Monosomy, the Loss of a Single Chromosome, May Have Severe Phenotypic Effects 8.3 Trisomy Involves the Addition of a Chromosome to a Diploid Genome Down Syndrome Patau Syndrome Edwards Syndrome Viability in Human Aneuploidy 8.4 Polyploidy, in Which More Than Two Haploid Sets of Chromosomes Are Present, Is Prevalent in Plants Autopolyploidy Allopolyploidy Endopolyploidy 8.5 Variation Occurs in the Composition and Arrangement of Chromosomes 8.6 A Deletion Is a Missing Region of a Chromosome Cri-du-Chat Syndrome in Humans Drosophila Heterozygous for Deficiencies May Exhibit Pseudodominance 8.7 A Duplication Is a Repeated Segment of the Genetic Material Gene Redundancy and Amplification: Ribosomal RNA Genes The Bar Mutation in Drosophila The Role of Gene Duplication in Evolution 8.8 Inversions Rearrange the Linear Gene Sequence Consequences of Inversions during Gamete Formation Position Effects of Inversions Evolutionary Advantages of Inversions 8.9 Translocations Alter the Location of Chromosomal Segments in the Genome Familial Down Syndrome in Humans 8.10 Fragile Sites in Humans Are Susceptible to Chromosome Breakage Fragile X Syndrome (Martin¿Bell Syndrome) 9 EXTRANUCLEAR INHERITANCE 9.1 Organelle Heredity Involves DNA in Chloroplasts and Mitochondria Chloroplasts: Variegation in Four O¿Clock Plants Chloroplast Mutations in Chlamydomonas Mitochondrial Mutations: The Case of poky in Neurospora Petites in Saccharomyces 9.2 Knowledge of Mitochondrial and Chloroplast DNA Helps Explain Organelle Heredity Organelle DNA and the Endosymbiotic Theory Molecular Organization and Gene Products of Chloroplast DNA Molecular Organization and Gene Products of Mitochondrial DNA 9.3 Mutations in Mitochondrial DNA Cause Human Disorders 9.4 Infectious Heredity Is Based on a Symbiotic Relationship between Host Organism and Invader Kappa in Paramecium Infective Particles in Drosophila 9.5 In Maternal Effects, the Maternal Genotype Has a Strong Influence during Early Development Ephestia Pigmentation Limnaea Coiling Embryonic Development in Drosophila 10 DNA STRUCTURE AND ANALYSIS 10.1 The Genetic Material Must Exhibit Four Characteristics 10.2 Until 1944, Observations Favored Protein as the Genetic Material 10.3 Evidence Favoring DNA as the Genetic Material Was First Obtained during the Study of Bacteria and Bacteriophages Transformation: Early Studies Transformation: The Avery, MacLeod and McCarty Experiment The Hershey¿Chase Experiment Transfection Experiments 10.4 Indirect and Direct Evidence Supports the Concept that DNA Is the Genetic Material in Eukaryotes Indirect Evidence: Distribution of DNA Indirect Evidence: Mutagenesis Direct Evidence: Recombinant DNA Studies 10.5 RNA Serves as the Genetic Material in Some Viruses 10.6 Knowledge of Nucleic Acid Chemistry Is Essential to the Understanding of DNA Structure Nucleotides: Building Blocks of Nucleic Acids Nucleoside Diphosphates and Triphosphates Polynucleotides 10.7 The Structure of DNA Holds the Key to Understanding Its Function Base Composition Studies X-Ray Diffraction Analysis The Watson¿Crick Model 10.8 Alternative Forms of DNA Exist 10.9 The Structure of RNA Is Chemically Similar to DNA, but Single Stranded 10.10 Many Analytical Techniques Have Been Useful during the Investigation of DNA and RNA Absorption of Ultraviolet Light (UV) Sedimentation Behavior Denaturation and Renaturation of Nucleic Acids Molecular Hybridization Fluorescent in situ Hybridization (FISH) Reassociation Kinetics and Repetitive DNA Electrophoresis of Nucleic Acids 11 DNA REPLICATION AND RECOMBINATION 11.1 DNA Is Reproduced by Semiconservative Replication The Meselson¿Stahl Experiment Semiconservative Replication in Eukaryotes Origins, Forks, and Units of Replication 11.2 DNA Synthesis in Bacteria Involves Five Polymerases, as well as Other Enzymes DNA Polymerase I Synthesis of Biologically Active DNA DNA Polymerase II, III, IV, and V 11.3 Many Complex Tasks Must Be Performed during DNA Replication Unwinding the DNA Helix Initiation of DNA Synthesis with an RNA Primer Continuous and Discontinuous Synthesis of Antiparallel Strands Concurrent Synthesis on the Leading and Lagging Strands Integrated Proofreading and Error Correction 11.4 A Summary of DNA Replication in Prokaryotes 11.5 Replication in Prokaryotes Is Controlled by a Variety of Genes 11.6 Eukaryotic DNA Synthesis Is Similar to Synthesis in Prokaryotes, but More Complex Multiple Replication Origins Eukaryotic DNA Polymerases 11.7 Telomeres Provide Structural Integrity at Chromosome Ends but Are Problematic to Replicate Replication at the Telomere 11.8 DNA Recombination, Like DNA Replication, Is Directed by Specific Enzymes 11.9 Gene Conversion Is a Consequence of DNA Recombination 12 DNA ORGANIZATION IN CHROMOSOMES 12.1 Viral and Bacterial Chromosomes Are Relatively Simple DNA Molecules 12.2 Supercoiling Facilitates Compaction of the DNA of Viral and Bacterial Chromosomes 12.3 Specialized Chromosomes Reveal Variations in the Organization of DNA Polytene Chromosomes Lampbrush Chromosomes 12.4 DNA Is Organized into Chromatin in Eukaryotes Chromatin Structure and Nucleosomes High-Resolution Studies of the Nucleosome Core Heterochromatin 12.5 Chromosome Banding Differentiates Regions along the Mitotic Chromosome 12.6 Eukaryotic Chromosomes Demonstrate Complex Sequence Organization Characterized by Repetitive DNA Satellite DNA Centromeric DNA Sequences Telomeric DNA Sequences Middle Repetitive Sequences: VNTRs and STRs Repetitive Transposed Sequences: SINEs and LINEs Middle Repetitive Multiple-Copy Genes 12.7 The Vast Majority of a Eukaryotic Genome Does Not Encode Functional Genes 13 RECOMBINANT DNA TECHNOLOGY AND GENE CLONING 13.1 Recombinant DNA Technology Combines Several Laboratory Techniques 13.2 Restriction Enzymes Cut DNA at Specific Recognition Sequences 13.3 Vectors Carry DNA Molecules to Be Cloned Plasmid Vectors Lambda (?) Phage Vectors Cosmid Vectors Bacterial Artificial Chromosomes Expressioon Vectors 13.4 DNA Was First Cloned in Prokaryotic Host Cells 13.5 Yeast Cells Are Used As Eukaryotic Hosts for Cloning 13.6 Plant and Animal Cells Can Be Used As Host Cells for Cloning Plant Cell Hosts Mammalian Cell Hosts 13.7 The Polymerase Chain Reaction Makes DNA Copies Without Host Cells Limitations of PCR Other Applications of PCR 13.8 Recombinant Libraries Are Collections of Cloned Sequences Genomic Libraries Chromosome-Specific Libraries cDNA Libraries 13.9 Specific Clones Can Be Recovered from a Library Probes Identify Specific Clones Screening a Library 13.10 Cloned Sequences Can Be Analyzed in Several Ways Restriction Mapping Nucleic Acid Blotting 13.11 DNA Sequencing Is the Ultimate Way to Characterize a Clone 14 THE GENETIC CODE AND TRANSCRIPTION 14.1 The Genetic Code [Uses Ribonucleotide Bases as ¿Letters¿] 14.2 Early Studies Established the Basic Operational Patterns of the Code The Triplet Nature of the Code The Nonoverlapping Nature of the Code The Commaless and Degenerate Nature of the Code 14.3 Studies by Nirenberg, Matthaei, and Others Led to Deciphering of the Code Synthesizing Polypeptides in a Cell-Free System Homopolymer Codes Mixed Copolymers The Triplet Binding Assay Repeating Copolymers 14.4 The Coding Dictionary Reveals Several Interesting Patterns among the 64 Codons Degeneracy and the Wobble Hypothesis The Ordered Nature of the Code Initiation, Termination, and Suppression 14.5 The Genetic Code Has Been Confirmed in Studies of Phage MS2 14.6 The Genetic Code Is Nearly Universal 14.7 Different Initiation Points Create Overlapping Genes 14.8 Transcription Synthesizes RNA on a DNA Template 14.9 Studies with Bacteria and Phages Provided Evidence for the Existence of mRNA 14.10 RNA Polymerase Directs RNA Synthesis Promoters, Template Binding, and the s Subunit Initiation, Elongation, and Termination of RNA Synthesis 14.11 Transcription in Eukaryotes Differs from Prokaryotic Transcription in Several Ways Initiation of Transcription in Eukaryotes Recent Discoveries Concerning RNA Polymerase Function Heterogeneous Nuclear RNA and Its Processing: Caps and Tails 14.12 The Coding Regions of Eukaryotic Genes Are Interrupted by Intervening Sequences Splicing Mechanisms: Autocatalytic RNAs Splicing Mechanisms: The Spliceosome RNA Editing Modifies the Final Transcript 14.13 Transcription Has Been Visualized by Electron Microscopy 15 TRANSLATION AND PROTEINS 15.1 Translation of mRNA Depends on Ribosomes and Transfer RNAs Ribosomal Structure tRNA Structure Charging tRNA 15.2 Translation of mRNA Can Be Divided into Three Steps Initiation Elongation Termination Polyribosomes 15.3 Crystallographic Analysis Has Revealed Many Details about the Functional Prokaryotic Ribosome 15.4 Translation Is More Complex in Eukaryotes 15.5 The Initial Insight That Proteins Are Important in Heredity Was Provided by the Study of Inborn Errors of Metabolism Phenylketonuiria 15.6 Studies of Neurospora Led to the One-Gene:One-Enzyme Hypothesis Analysis of Neurospora Mutants by Beadle and Tatum Genes and Enzymes: Analysis of Biochemical Pathways 15.7 Studies of Human Hemoglobin Established That One Gene Encodes One Polypeptide Sickle-Cell Anemia Human Hemoglobins 15.8 The Nucleotide Sequence of a Gene and the Amino Acid Sequence of the Corresponding Protein Exhibit Colinearity 15.9 Variation in Protein Structure Provides the Basis of Biological Diversity 15.10 Posttranslational Modification Alters the Final Protein Product 15.11 Protein Function in Many Diverse Roles 15.12 Proteins Are Made Up of One or More Functional Domains Exon Shuffling The Origin of Protein Domains 16 GENE MUTATION AND DNA REPAIR 16.1 Gene Mutations Are Classified in Various Ways Spontaneous and Induced Mutations Classification Based on Location of Mutation Classification Based on Type of Molecular Change Classification Based on Phenotypic Effects 16.2 Spontaneous Mutations Arise from Replication Errors and Base Modifications DNA Replication Errors Replication Slippage Tautomeric Shifts Depurination and Deamination Oxidative Damage Transposons 16.3 Induced Mutations Arise from DNA Damage Caused by Chemicals and Radiation Base Analogs Alkylating Agents and Acridine Dyes Ultraviolet Light Ionizing Radiation 16.4 Genomics and Gene Sequencing Have Enhanced Our Understanding of Mutations in Humans ABO Blood Groups Muscular Dystrophy Fragile X Syndrome, Myotonic Dystrophy, and Huntington Disease 16.5 The Ames Test Is Used to Assess the Mutagenicity of Compounds 16.6 Organisms Use DNA Repair Systems to Counteract Mutations Proofreading and Mismatch Repair Postreplication Repair and the SOS Repair System Photoreactivation Repair: Reversal of UV Damage Base and Nucleotide Excision Repair Nucleotide Excision Repair and Xeroderma Pigmentosum in Humans Double-Strand Break Repair in Eukaryotes 16.7 Geneticists Use Mutations to Identify Genes and Study Gene Function 17 REGULATION OF GENE EXPRESSION IN PROKARYOTES 17.1 Prokaryotes Regulate Gene Expression in Response to Environmental Conditions 17.2 Lactose Metabolism in E. coli Is Regulated by an Inducible System Structural Genes The Discovery of Regulatory Mutations The Operon Model: Negative Control Genetic Proof of the Operon Model Isolation of the Repressor 17.3 The Catabolite-Activating Protein (CAP) Exerts Positive Control over the lac Operon 17.4 Crystal Structure Analysis of Repressor Complexes Has Confirmed the Operon Model 17.5 The Tryptophan (trp) Operon in E. coli Is a Repressible Gene System Evidence for the trp Operon 17.6 Attenuation Is a Critical Process in Regulation of the trp Operon in E. coli 17.7 TRAP and AT Proteins Govern Attenuation in B. subtilis 17.8 The ara Operon Is Controlled by a Regulator Protein That Exerts Both Positive and Negative Control 18 REGULATION OF GENEEXPRESSION IN EUKARYOTES 18.1 Eukaryotic Gene Regulation Can Occur at Any of the Steps Leading from DNA to Protein Product 18.2 Eukaryotic Gene Expression Is Influenced by Chromosome Organization and Chromatin Modifications Chromatin Remodeling DNA Methylation 18.3 Eukaryotic Gene Transcription Is Regulated at Specific Cis-Acting Sites Promoters Enhancers and Silencers 18.4 Eukaryotic Transcription Is Regulated by Transcription Factors that Bind to Cis-Acting Sites The Human Metallothionein IIA Gene: Multiple Cis-Acting Elements and Transcription Factors Functional Domains of Eukaryotic Transcription Factors 18.5 Activators and Repressors Regulate Transcription by Binding to Cis-acting Sites and Interacting with Other Transcription Factors Formation of the Transcription Initiation Complex Interactions of the General Transcription Factors with Transcription Activators 18.6 Gene Regulation in a Model Organism: Inducible Transcription of the GAL Genes of Yeast 18.7 Post-transcriptional Gene Regulation Occurs at All the Steps from RNA Processing to Protein Modification Alternative Splicing of mRNA Control of mRNA Stability 18.8 RNA Silencing Controls Gene Expression in Several Ways RNA Silencing in Biotechnology and Therapy 19 DEVELOPMENTAL GENETICS OF MODEL ORGANISMS 19.1 Developmental Genetics Seeks to Explain How a Differentiated State Develops from Genomic Patterns of Expression 19.2 Evolutionary Conservation of Developmental Mechanisms Can Be Studied Using Model Organisms Model Organisms in the Study of Development Analysis of Developmental Mechanisms Basic Concepts in Developmental Genetics 19.3 Genetic Analysis of Embryonic Development in Drosophila Revealed How the Body Axis of Animals Is Specified Overview of Drosophila Development Genetic Analysis of Embryogenesis 19.4 Zygotic Genes Program Segment Formation in Drosophila Gap Genes Pair-Rule Genes Segment Polarity Genes Segmentation Genes in Mice and Humans 19.5 Homeotic Selector Genes Specify Parts of the Adult Body Hox Genes in Drosophila Hox Genes and Human Genetic Disorders Control of Hox Gene Expression 19.6 Cascades of Gene Action Control Differentiation 19.7 Plants Have Evolved Systems That Parallel the Hox Genes of Animals Homeotic Genes in Arabidopsis Evolutionary Divergence in Homeotic Genes 19.8 Cell¿Cell Interactions in Development Are Modeled in C. elegans Signaling Pathways in Development The Notch Signaling Pathway Overview of C. elegans Development Genetic Analysis of Vulva Formation Notch Signaling Systems in Humans 19.9 Transcriptional Networks Control Gene Expression in Development A General Model of a Transcription Network Transcriptional Networks in Drosophila Segmentation 20 CANCER AND REGULATION OF THE CELL CYCLE 20.1 Cancer Is a Genetic Disease That Arises at the Level of Somatic Cells What Is Cancer? The Clonal Origin of Cancer Cells Cancer As a Multistep Process, Requiring Multiple Mutations 20.2 Cancer Cells Contain Genetic Defects Affecting Genomic Stability, DNA Repair, and Chromatin Modifications 0.3 Cancer Cells Contain Genetic Defects Affecting Cell-Cycle Regulation The Cell Cycle and Signal Transduction Cell-Cycle Control and Checkpoints 20.4 Many Cancer-Causing Genes Disrupt Control of the Cell Cycle The ras Proto-oncogenes The cyclin D1 and cyclin E Proto-oncogenes The p53 Tumor Suppressor Gene The RB1 Tumor Suppressor Gene 20.5 Cancer Cells Metastasize, Invading Other Tissues 20.6 Predisposition to Some Cancers Can Be Inherited 20.7 Viruses Contribute to Cancer in Both Humans and Animals 20.8 Environmental Agents Contribute to Human Cancers 21 GENOMICS, PROTEOMICS, AND BIOINFORMATICS 21.1 Whole-Genome Shotgun Sequencing Is a Widely Used Method for Sequencing and Assembling Entire Genomes High-Throughput Sequencing The Clone-by-Clone Approach Draft Sequences and Checking for Errors 21.2 DNA Sequence Analysis Relies on Bioinformatics Applications and Genome Databases Annotation to Identify Gene Sequences Hallmark Characteristics of a Gene Sequence Can Be Recognized During Annotation 21.3 Functional Genomics Attempts to Identify Potential Functions of Genes and Other Elements in a Genome Predicting Gene and Protein Functions by Sequence Analysis Predicting Function from Analysis of Protein Domains and Motifs 21.4 The Human Genome Project Reveals Many Important Aspects of Genome Organization in Humans Origins of the Project Major Features of the Human Genome 21.5 The ¿Omics¿ Revolution Has Created a New Era of Biological Research Methods 21.6 Prokaryotic and Eukaryotic Genomes Display Common Structural and Functional Features and Important Differences Unexpected Features of Prokaryotic Genomes Organizational Patterns of Eukaryotic Genomes The Yeast Genome The Arabidopsis Genome The Minimum Genome for Living Cells 21.7 Comparative Genomics Analyzes and Compares Genomes from Different Organisms The Dog as a Model Organism The Chimpanzee Genome The Rhesus Monkey Genome The Sea Urchin Genome Evolution and Function of Multigene Families 21.8 Metagenomics Applies Genomics Techniques to Environmental Samples 21.9 Transcriptome Analysis Reveals Profiles of Expressed Genes in Cells and Tissues 21.10 Proteomics Identifies and Analyzes the Protein Composition of Cells Reconciling the Number of Genes and the Number of Proteins Expressed by a Cell or Tissue Proteomics Technologies: Two-Dimensional Gel Electrophoresis for Separating Proteins Proteomics Technologies: Mass Spectrometry for Protein Identification Identification of Collagen in Tyrannosaurus rex and Mammut americanum Environment-Induced Changes in the M. genitalium Proteome21.11 Systems Biology Is an Integrated Approach to Study Interactions of All Components of an Organism¿s Cells 22 GENOME DYNAMICS: TRANSPOSONS, IMMUNOGENETICS, AND EUKARYOTIC VIRUSES 22.1 Transposable Elements Are Present in the Genomes of Both Prokaryotes and Eukaryotes Insertion Sequences Bacterial Transposons The Ac¿Ds System in Maize Mobile Genetic Elements in Peas: Mendel Revisited Copia Elements in Drosophila P Element Transposons in Drosophila Transposable Elements in Humans 22.2 Transposons Use Two Different Methods to Move Within Genomes DNA Transposons and Transposition Retrotransposons and Transposition 22.3 Transposons Create Mutations and Provide Raw Material for Evolution Transposon Silencing Transposons, Mutations, and Gene Expression Transposons and Evolution 22.4 Immunoglobulin Genes Undergo Programmed Genome Rearrangements The Immune System and Antibody Diversity Immunoglobulin and TCR structure The Generation of Antibody Diversity and Class Switching 22.5 Eukaryotic Viruses Shuttle Genes Within and Between Genomes 22.6 Retroviruses Move Genes In and Out of Genomes and Alter Host Gene Expression. The Retroviral Life Cycle Retroviral Repercussions for Genome Rearrangement 22.7 Large DNA Viruses Gain Genes by Recombining with Other Host and Viral Genomes Gene transfer between cellular and viral genomes Gene transfer between viruses 22.8 RNA Viruses Acquire Host Genes and Evolve New Forms The Life Cycle of RNA Viruses Gene Transfer and Genome Variability in RNA Viruses 23 GENOMIC ANALYSIS ¿ DISSECTION OF GENE FUNCTION 23.1 Geneticists Use Model Organisms to Answer Genetic and Genomic Questions Features of Genetic Model Organisms Yeast as a Genetic Model Organism Drosophila as a Genetic Model Organism The Mouse as a Genetic Model Organism 23.2 Geneticists Dissect Gene Function Using Mutations and Forward Genetics Generating Mutants with Radiation, Chemicals, and Transposon Insertion Screening for Mutants Selecting for Mutants Defining the Genes Dissecting Genetic Networks and Pathways Extending the Analysis: Suppressors and Enhancers Extending the Analysis: Cloning the Genes Extending the Analysis: Biochemical Functions 23.3 Geneticists Dissect Gene Function Using Genomics and Reverse Genetics Genetic Analysis Beginning with a Purified Protein Genetic Analysis Beginning with a Mutant Model Organism Genetic Analysis Beginning with the Cloned Gene or DNA Sequence Genetic Analysis Using Gene-Targeting Technologies 23.4 Geneticists Dissect Gene Function Using RNAi, Functional Genomic, and Systems Biology Technologies RNAi: Genetics without Mutations High-Throughput and Functional Genomics Techniques Gene Expression Microarrays Genome-Wide Mapping of Protein¿DNA Binding Sites: ChIP-on-Chip Systems Biology and Gene Networks 24 APPLICATIONS AND ETHICS OF GENETIC ENGINEERING AND BIOTECHNOLOGY 24.1 Genetically Engineered Organisms Synthesize a Wide Range of Biological and Pharmaceutical Products Transgenic Animal Hosts and Pharmaceutical Products Recombinant DNA Approaches for Vaccine Production and Transgenic Plants with Edible Vaccines 24.2 Genetic Engineering of Plants Has Revolutionized Agriculture Transgenic Crops for Herbicide and Pest Resistance Nutritional Enhancement of Crop Plants 24.3 Transgenic Animals with Genetically Enhanced Characteristics Have the Potential to Serve Important Roles in Agriculture and Biotechnology 24.4 Genetic Engineering and Genomics Are Transforming Medical Diagnosis Genetic Tests Based on Restriction Enzyme Analysis Genetic Tests Using Allele-Specific Oligonucleotides Genetic Testing Using DNA Microarrays and Genome Scans Genetic Analysis Using Gene Expression Microarrays Application of Microarrays for Gene Expression and Genotype Analysis of Pathogens 24.5 Genetic Engineering and Genomics Promise New, More Targeted Medical Therapies Pharmacogenomics and Rational Drug Design Gene Therapy 24.6 DNA Profiles Help Identify Individuals DNA Profiling Based on DNA Microsatellites Terrorism and Natural Disasters Force Development of New Technologies World Trade Center South Asian Tsunami Forensic Applications of DNA Profiling 24.7 Genetic Engineering, Genomics, and Biotechnology Create Ethical, Social, and Legal Questions Concerns about Genetically Modified Organisms and GM Foods Genetic Testing and Ethical Dilemmas The Ethical Concerns Surrounding Gene Therapy The Ethical, Legal, and Social Implications (ELSI) Program DNA and Gene Patents 25 QUANTITATIVE GENETICS AND MULTIFACTORIAL TRAITS 25.1 Not All Polygenic Traits Show Continuous Variation 25.2 Quantitative Traits Can Be Explained in Mendelian Terms The Multiple-Gene Hypothesis for Quantitative Inheritance Additive Alleles: The Basis of Continuous Variation Calculating the Number of Polygenes 25.3 The Study of Polygenic Traits Relies on Statistical Analysis The Mean Variance Standard Deviation Standard Error of the Mean Covariance Analysis of a Quantitative Character 25.4 Heritability Values Estimate the Genetic Contribution to Phenotypic Variability Broad-Sense Heritability Narrow-Sense Heritability Artificial Selection 25.5 Twin Studies Allow an Estimation of Heritability in Humans 25.6 Quantitative Trait Loci Can Be Mapped 26 GENETICS AND BEHAVIOR 26.1 Behavioral Differences Between Genetic Strains Can Be Identified Inbred Mouse Strains: Differences in Alcohol Preference Emotional Behavior Differences in Inbred Mouse Strains 26.2 Selection Can Establish Genetic Strains with Behavioral Differences Maze Learning in Rats Selected Lines for Geotaxis in Drosophila 26.3 Drosophila Is a Model Organism for Behavior Genetics Genetic Control of Courtship Dissecting Behavior with Genetic Mosaics Functional Analysis of the Nervous System Drosophila Can Learn and Remember 26.4 Human Behavior Has Genetic Components Single Genes and Behavior: Huntington Disease A Transgenic Mouse Model of Huntington Disease Mechanisms of Huntington Disease Multifactorial Behavioral Traits: Schizophrenia 27 POPULATION GENETICS 27.1 Allele Frequencies in Population Gene Pools Vary in Space and Time 27.2 The Hardy¿Weinberg Law Describes the Relationship between Allele Frequencies and Genotype Frequencies in an Ideal Population 27.3 The Hardy¿Weinberg Law Can Be Applied to Human Populations Calculating an Allele¿s Frequency Testing for Hardy¿Weinberg Equilibrium 27.4 The Hardy¿Weinberg Law Can Be Used to Study Multiple Alleles, X-Linked Traits, and Heterozygote Frequencies Calculating Frequencies for Multiple Alleles in Hardy¿Weinberg Populations Calculating Frequencies for X-linked Traits Calculating Heterozygote Frequency 27.5 Natural Selection Is a Major Force Driving Allele Frequency Change Natural Selection Fitness and Selection Selection in Natural Populations Natural Selection and Quantitative Traits 27.6 Mutation Creates New Alleles in a Gene Pool 27.7 Migration and Gene Flow Can Alter Allele Frequencies 27.8 Genetic Drift Causes Random Changes in Allele Frequency in Small Populations Founder Effects in Human Populations Allele Loss during a Bottleneck 27.9 Nonrandom Mating Changes Genotype Frequency but Not Allele Frequency Coefficient of Inbreeding Outcomes of Inbreeding 28 EVOLUTIONARY GENETICS 28.1 Speciation Can Occur by Transformation or by Splitting Gene Pools 28.2 Most Populations and Species Harbor Considerable Genetic Variation Artificial Selection Variations in Amino Acid Sequence Variations in Nucleotide Sequence Explaining the High Level of Genetic Variation in Populations 28.3 The Genetic Structure of Populations Changes across Space and Time 28.4 Defining a Species Is a Challenge for Evolutionary Biology 28.5 Reduced Gene Flow, Selection, and Genetic Drift Can Lead to Speciation Examples of Speciation The Minimum Genetic Divergence for Speciation The Rate of Speciation 28.6 Genetic Differences Can Be Used to Reconstruct Evolutionary History Constructing Evolutionary Trees from Genetic Data Molecular Clocks 28.7 Reconstructing Evolutionary History Allows Us to Answer Many Questions Transmission of HIV Neanderthals and Modern Humans Neanderthal Genomics 29 CONSERVATION GENETICS 29.1 Genetic Diversity Is the Goal of Conservation Genetics Loss of Genetic Diversity Identifying Genetic Diversity 29.2 Population Size Has a Major Impact on Species Survival 29.3 Genetic Effects Are More Pronounced in Small, Isolated Populations Genetic Drift Inbreeding Reduction in Gene Flow 29.4 Genetic Erosion Threatens Species Survival 29.5 Conservation of Genetic Diversity Is Essential to Species Survival Ex Situ Conservation: Captive Breeding Rescue of the Black-Footed Ferret through Captive Breeding Ex Situ Conservation and Gene Banks In Situ Conservation Population Augmentation ER -