Concepts of Genetics

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