Genetic Analysis: An Integrated Approach

Cover
Brief Table of Contents
Title Page
Copyright Page
Table of Contents
About the Authors
Dedication
Preface
Chapter 1 The Molecular Basis of Heredity, Variation, and Evolution
1.1 Modern Genetics Is in Its Second Century
The Development of Modern Genetics
The Four Phases of Modern Genetics
Genetics—Central to Modern Biology
1.2 The Structure of DNA Suggests a Mechanism for Replication
The Discovery of DNA Structure
DNA Nucleotides
DNA Replication
Genetic Analysis 1.1
Experimental Insight 1.1
1.3 DNA Transcription and Messenger RNA Translation Express Genes
Transcription
Translation
Genetic Analysis 1.2
1.4 Genetic Variation Can Be Detected by Examining DNA, RNA, and Proteins
Gel Electrophoresis
Stains, Blots, and Probes
DNA Sequencing and Genomics
Proteomics and Other “‐omic” Analyses
1.5 Evolution Has a Genetic Basis
Darwin’s Theory of Evolution
Four Evolutionary Processes
Tracing Evolutionary Relationships
Genetic Analysis 1.3
Case Study Ancient Dna: Genetics Looks into the Past
Summary 
Preparing for Problem Solving
 Problems
Chapter 2 Transmission Genetics
2.1 Gregor Mendel Discovered the Basic Principles of Genetic Transmission
Mendel’s Modern Experimental Approach
Five Critical Experimental Innovations
2.2 Monohybrid Crosses Reveal the Segregation of Alleles
Identifying Dominant and Recessive Traits
Evidence of Particulate Inheritance and Rejection of the Blending Theory
Segregation of Alleles
Hypothesis Testing by Test‐Cross Analysis
Hypothesis Testing by F2 Self-Fertilization
Genetic Analysis 2.1
2.3 Dihybrid and Trihybrid Crosses Reveal the Independent Assortment of Alleles
Dihybrid‐Cross Analysis of Two Genes
Experimental Insight 2.1
Testing Independent Assortment by Test‐Cross Analysis
Genetic Analysis 2.2
Testing Independent Assortment by Trihybrid‐Cross Analysis
The Rediscovery of Mendel’s Work
Experimental Insight 2.2
2.4 Probability Theory Predicts Mendelian Ratios
The Product Rule
The Sum Rule
Conditional Probability
Binomial Probability
2.5 Chi‐Square Analysis Tests the Fit between Observed Values and Expected Outcomes
Chi‐Square Analysis
Chi‐Square Analysis of Mendel’s Data
2.6 Autosomal Inheritance and ‐Molecular Genetics Parallel the Predictions of Mendel’s Hereditary Principles
Autosomal Dominant Inheritance
Autosomal Recessive Inheritance
Prospective and Retrospective Predictions in Human Genetics
Molecular Genetics of Mendel’s Traits
Genetic Analysis 2.3
Case Study Omim, Gene Mutations, and Human Hereditary Disease
Summary 
Preparing for Problem Solving 
Problems
Chapter 3 Cell Division and Chromosome Heredity
3.1 Mitosis Divides Somatic Cells
The Cell Cycle
Substages of M Phase
Chromosome Movement and Distribution
Completion of Cell Division
Cell Cycle Checkpoints
3.2 Meiosis Produces Cells for Sexual Reproduction
Meiosis Features Two Cell Divisions
Meiosis I
Meiosis II
Meiosis Generates Mendelian Ratios
3.3 The Chromosome Theory of Heredity Proposes That Genes Are Carried on Chromosomes
Genetic Analysis 3.1
X‐Linked Inheritance
Testing the Chromosome Theory of Heredity
3.4 Sex Determination Is Chromosomal and Genetic
Sex Determination in Drosophila
Genetic Analysis 3.2
Mammalian Sex Determination
Diversity of Sex Determination
Experimental Insight 3.1
3.5 Human Sex‐Linked Transmission Follows Distinct Patterns
Expression of X‐Linked Recessive Traits
X‐Linked Dominant Trait Transmission
Y‐Linked Inheritance
Genetic Analysis 3.3
3.6 Dosage Compensation Equalizes the Expression of Sex‐Linked Genes
Case Study The (Degenerative) Evolution of the Mammalian Y Chromosome
Summary
Preparing for Problem Solving
Problems
Chapter 4 Gene Interaction
4.1 Interactions between Alleles Produce Dominance Relationships
The Molecular Basis of Dominance
Functional Effects of Mutation
Notational Systems for Genes and Allele Relationships
Incomplete Dominance
Codominance
Dominance Relationships of ABO Alleles
Genetic Analysis 4.1
Allelic Series
Lethal Alleles
Delayed Age of Onset
4.2 Some Genes Produce Variable Phenotypes
Sex‐Limited Traits
Sex‐Influenced Traits
Incomplete Penetrance
Variable Expressivity
Gene–Environment Interactions
Pleiotropic Genes
4.3 Gene Interaction Modifies Mendelian Ratios
Gene Interaction in Pathways
The One Gene–One Enzyme Hypothesis
Experimental Insight 4.1
Genetic Dissection to Investigate Gene Action
Genetic Analysis 4.2
Epistasis and Its Results
4.4 Complementation Analysis Distinguishes Mutations in the Same Gene from Mutations in Different Genes
Genetic Analysis 4.3
Case Study Complementation Groups in a Human Cancer‐Prone Disorder
Summary 
Preparing for Problem Solving  
Problems
Chapter 5 Genetic Linkage and Mapping in Eukaryotes
5.1 Linked Genes Do Not Assort Independently
Detecting Genetic Linkage
The Discovery of Genetic Linkage
Detecting Autosomal Genetic Linkage through Test‐Cross Analysis
Cytological Evidence of Recombination
Genetic Analysis 5.1
5.2 Genetic Linkage Mapping Is Based on Recombination Frequency between Genes
The First Genetic Linkage Map
Map Units
Chi‐Square Analysis of Genetic Linkage Data
5.3 Three‐Point Test‐Cross Analysis Maps Genes
Identifying Parental, Single‐Crossover, and Double‐‐Crossover Gametes in Three‐Point Mapping
Constructing a Three‐Point Recombination Map
Determining Gamete Frequencies from Genetic Maps
Correction of Genetic Map Distances
Genetic Analysis 5.2
5.4 Multiple Factors Cause Recombination to Vary
Sex Affects Recombination
Recombination Is Dominated by Hotspots
Genome Sequence Analysis Reveals Recombination Hotspot Distribution
5.5 Human Genes Are Mapped Using Specialized Methods
Mapping with Genetic Markers
The Inheritance of Disease‐Causing Genes Linked to Genetic Markers
Allelic Phase
Lod Score Analysis
Experimental Insight 5.1
Genetic Analysis 5.3
Genome‐Wide Association Studies
Linkage Disequilibrium and Evolutionary Analysis
Case Study Mapping the Gene for Cystic Fibrosis
Summary
Preparing for Problem Solving  
Problems
Chapter 6 Genetic Analysis and Mapping in Bacteria and Bacteriophages
6.1 Specialized Methods Are Used for Genetic Analysis of Bacteria
Bacterial Culture and Growth Analysis
Characteristics of Bacterial Genomes
Plasmids in Bacterial Cells
Research Technique 6.1
6.2 Bacteria Transfer Genes by Conjugation
Conjugation Identified
Transfer of the F Factor
Formation of an Hfr Chromosome
Hfr Gene Transfer
Interrupted Mating and Time‐of‐Entry Mapping
Time‐of‐Entry Mapping Experiments
Genetic Analysis 6.1
Consolidation of Hfr Maps
Conjugation with F Strains Produces Partial Diploids
Plasmids and Conjugation in Archaea
6.3 Bacterial Transformation Produces Genetic Recombination
Genetic Analysis 6.2
Steps in Transformation
Mapping by Transformation
6.4 Bacterial Transduction Is Mediated by Bacteriophages
Bacteriophage Life Cycles
Generalized Transduction
Cotransduction
Cotransduction Mapping
Specialized Transduction
6.5 Bacteriophage Chromosomes Are Mapped by Fine‐Structure Analysis
Genetic Analysis 6.3
Genetic Complementation Analysis
Intragenic Recombination Analysis
Deletion‐Mapping Analysis
6.6 Lateral Gene Transfer Alters Genomes
Lateral Gene Transfer and Genome Evolution
Identifying Lateral Gene Transfer in Genomes
Case Study The Evolution of Antibiotic Resistance and Its Impact on Medical Practice
Summary
Preparing for Problem Solving
Problems
APPLICATION A Human Hereditary Disease and Genetic Counseling
A.1 Hereditary Disease and Disease Genes
Types of Hereditary Disease
Genetic Testing and Diagnosis
A.2 Genetic Counseling
Indicators and Goals of Genetic Counseling
Assessing and Communicating Risks and Options
Ethical Issues in Genetic Medicine
Genetic Counseling and Ethical Issues
In Closing
Problems
Chapter 7 DNA Structure and Replication
7.1 DNA Is the Hereditary Molecule of Life
Chromosomes Contain DNA
A Transformation Factor Responsible for Heredity
DNA Is the Transformation Factor
DNA Is the Hereditary Molecule
7.2 The DNA Double Helix Consists of Two Complementary and Antiparallel Strands
DNA Nucleotides
The DNA Duplex
Genetic Analysis 7.1
7.3 DNA Replication Is Semiconservative and Bidirectional
Three Competing Models of Replication
The Meselson–Stahl Experiment
Origin and Directionality of Replication in Bacterial DNA
Multiple Replication Origins in Eukaryotes
7.4 DNA Replication Precisely Duplicates the Genetic Material
DNA Sequences at Replication Origins
Molecular Biology of Replication Initiation
Continuous and Discontinuous Strand Replication
RNA Primer Removal and Okazaki Fragment Ligation
Synthesis of Leading and Lagging Strands at the Replication Fork
DNA Proofreading
Supercoiling and Topoisomerases
Replication at the Ends of Linear Chromosomes
Genetic Analysis 7.2
7.5 Methods of Molecular Genetic Analysis Make Use of DNA Replication Processes
The Polymerase Chain Reaction
Separation of PCR Products
Dideoxynucleotide DNA Sequencing
New Generations of DNA Sequencing Technology
Genetic Analysis 7.3
Case Study Dna Helicase Gene Mutations and Human Progeroid Syndrome
Summary
Preparing for Problem Solving 
Problems
Chapter 8 Molecular Biology of Transcription and RNA Processing
8.1 RNA Transcripts Carry the Messages of Genes
RNA Nucleotides and Structure
Experimental Discovery of Messenger RNA
Categories of RNA
8.2 Bacterial Transcription Is a Four‐Stage Process
Bacterial RNA Polymerase
Bacterial Promoters
Transcription Initiation
Genetic Analysis 8.1
Transcription Elongation and Termination
Transcription Termination Mechanisms
8.3 Eukaryotic Transcription Is More Diversified and Complex than Bacterial Transcription
Polymerase II Transcription of mRNA in Eukaryotes
Research Technique 8.1
Pol II Promoter Recognition
Detecting Promoter Consensus Elements
Other Regulatory Sequences and Chromatin‐Based Regulation of RNA Pol II Transcription
RNA Polymerase I Promoters
RNA Polymerase III Promoters
Archaeal Promoters and Transcription
The Evolutionary Implications of Comparative Transcription
8.4 Posttranscriptional Processing Modifies RNA Molecules
Capping Pre‐mRNA
Polyadenylation of Pre‐mRNA
The Torpedo Model of Transcription Termination
Introns
Pre‐mRNA Splicing
Splicing Signal Sequences
A Gene Expression Machine Couples Transcription and Pre‐mRNA Processing
Alternative Patterns of RNA Transcription and Alternative RNA Splicing
Self‐Splicing Introns
Genetic Analysis 8.2
Ribosomal RNA Processing
Transfer RNA Processing
RNA Editing
Case Study Sexy Splicing: Alternative mrna Splicing and Sex Determination in Drosophila
Summary
Preparing for Problem Solving
Problems
Chapter 9 The Molecular Biology of Translation
9.1 Polypeptides Are Amino Acid Chains That Are Assembled at Ribosomes
Amino Acid Structure
Polypeptide and Transcript Structure
Ribosome Structures
A Three‐Dimensional View of the Ribosome
Research Technique 9.1
9.2 Translation Occurs in Three Phases
Translation Initiation
Polypeptide Elongation
Genetic Analysis 9.1
Translation Termination
9.3 Translation Is Fast and Efficient
The Translational Complex
Translation of Polycistronic mRNA
9.4 The Genetic Code Translates Messenger RNA into Polypeptide
The Genetic Code Displays Third‐Base Wobble
The (Almost) Universal Genetic Code
Genetic Analysis 9.2
Charging tRNA Molecules
Protein Folding and Posttranslational Polypeptide Processing
The Signal Hypothesis
9.5 Experiments Deciphered the Genetic Code
No Overlap in the Genetic Code
A Triplet Genetic Code
No Gaps in the Genetic Code
Deciphering the Genetic Code
Genetic Analysis 9.3
Case Study Antibiotics and Translation Interference
Summary  
Preparing for Problem Solving 
Problems
APPLICATION B Human Genetic Screening
B.1 Presymptomatic Diagnosis of Huntington’s Disease
Trinucleotide Repeat Expansion
Detecting the Number of Repeats
B.2 Newborn Genetic Screening
Phenylketonuria and the First Newborn Genetic Test
Living with PKU
The Recommended Uniform Screening Panel
B.3 Genetic Testing to Identify Carriers
Testing Blood Proteins
DNA‐Based Carrier Screening and Diagnostic Verification
Carrier Screening Criteria
Pharmacogenetic Screening
B.4 Prenatal Genetic Testing
Invasive Screening Using Amniocentesis or Chorionic Villus Sampling
Noninvasive Prenatal Testing
Maternal Serum Screening
Preimplantation Genetic Screening
B.5 Direct‐to‐Consumer Genetic Testing
B.6 Opportunities and Choices
Problems
Chapter 10 Eukaryotic Chromosome Abnormalities and Molecular Organization
10.1 Chromosome Number and Shape Vary among Organisms
Chromosomes in Nuclei
Chromosome Visualization
Chromosome Banding
Heterochromatin and Euchromatin
10.2 Nondisjunction Leads to Changes in Chromosome Number
Chromosome Nondisjunction
Gene Dosage Alteration
Genetic Analysis 10.1
Aneuploidy in Humans
Mosaicism
Uniparental Disomy
10.3 Changes in Euploid Content Lead to Polyploidy
Causes of Autopolyploidy and Allopolyploidy
Genetic Analysis 10.2
Consequences of Polyploidy
Polyploidy and Evolution
10.4 Chromosome Breakage Causes Mutation by Loss, Gain, and Rearrangement of Chromosomes
Partial Chromosome Deletion
Unequal Crossover
Detecting Duplication and Deletion
Deletion Mapping
10.5 Chromosome Breakage Leads to Inversion and Translocation of Chromosomes
Chromosome Inversion
Genetic Analysis 10.3
Experimental Insight 10.1
Chromosome Translocation
10.6 Eukaryotic Chromosomes Are Organized into Chromatin
Chromatin Compaction
Histone Proteins and Nucleosomes
Higher Order Chromatin Organization and Chromosome Structure
Nucleosome Disassembly, Synthesis, and Reassembly during Replication
Position Effect Variegation: Effect of Chromatin State on Transcription
Case Study Human Chromosome Evolution
Summary
Preparing for Problem Solving 
Problems
Chapter 11 Gene Mutation, DNA Repair, and Homologous Recombination
11.1 Mutations Are Rare and Random and Alter DNA Sequence
Proof of the Random Mutation Hypothesis
Germ‐Line and Somatic Mutations
Point Mutations
Base‐Pair Substitution Mutations
Frameshift Mutations
Regulatory Mutations
Experimental Insight 11.1
Forward Mutation and Reversion
11.2 Gene Mutations May Arise from Spontaneous Events
Spontaneous DNA Replication Errors
Genetic Analysis 11.1
Spontaneous Nucleotide Base Changes
11.3 Mutations May Be Caused by Chemicals or Ionizing Radiation
Chemical Mutagens
Radiation‐Induced DNA Damage
The Ames Test
11.4 Repair Systems Correct Some DNA Damage
Direct Repair of DNA Damage
Genetic Analysis 11.2
DNA Damage‐Signaling Systems
11.5 Proteins Control Translesion DNA Synthesis and the Repair of Double‐Strand Breaks
Translesion DNA Synthesis
Double‐Strand Break Repair
11.6 DNA Double‐Strand Breaks Initiate Homologous Recombination
The Holliday Model
The Bacterial RecBCD Pathway
The Double‐Stranded Break Model of Homologous Recombination
11.7 Transposable Genetic Elements Move throughout the Genome
The Characteristics and Classification of Transposable Elements
The Mutagenic Effect of Transposition
Transposable Elements in Bacterial Genomes
Transposable Elements in Eukaryotic Genomes
The Discovery of Ds and Ac Elements in Maize
Genetic Analysis 11.3
Drosophila P Elements
Retrotransposons
Case Study Mendel’s Peas Are Shaped by Transposition
Summary
Preparing for Problem Solving 
Problems
Chapter 12 Regulation of Gene Expression in Bacteria and Bacteriophage
12.1 Transcriptional Control of Gene Expression Requires DNA–Protein Interaction
Negative and Positive Control of Transcription
Regulatory DNA‐Binding Proteins
12.2 The lac Operon Is an Inducible Operon System under Negative and Positive Control
Lactose Metabolism
lac Operon Structure
lac Operon Function
12.3 Mutational Analysis Deciphers Genetic Regulation of the lac Operon
Analysis of Structural Gene Mutations
lac Operon Regulatory Mutations
Molecular Analysis of the lac Operon
Genetic Analysis 12.1
Experimental Insight 12.1
12.4 Transcription from the Tryptophan Operon Is Repressible and Attenuated
Feedback Inhibition of Tryptophan Synthesis
Attenuation of the trp Operon
Attenuation Mutations
Attenuation in Other Amino Acid Operon Systems
12.5 Bacteria Regulate the Transcription of Stress Response Genes and Also Translation
Alternative Sigma Factors and Stress Response
Genetic Analysis 12.2
Translational Regulation in Bacteria
12.6 Riboswitches Regulate Bacterial Transcription, Translation, and mRNA Stability
Riboswitch Regulation of Transcription
Riboswitch Regulation of Translation
Riboswitch Control of mRNA Stability
12.7 Antiterminators and Repressors Control Lambda Phage Infection of E. coli
The Lambda Phage Genome
Early Gene Transcription
Cro Protein and the Lytic Cycle
The Repressor Protein and Lysogeny
Resumption of the Lytic Cycle following Lysogeny Induction
Case Study Vibrio cholerae—Stress Response Leads to Serious Infection Through Positive Control of Transcription
Summary
Preparing for Problem Solving
Problems
Chapter 13 Regulation of Gene Expression in Eukaryotes
13.1 Cis‐Acting Regulatory Sequences Bind Trans‐Acting Regulatory Proteins to Control Eukaryotic Transcription
Overview of Transcriptional Regulatory Interactions in Eukaryotes
Integration and Modularity of Eukaryotic Regulatory Sequences
Locus Control Regions
Enhancer‐Sequence Conservation
Yeast as a Simple Model for Eukaryotic Transcription
Insulator Sequences
13.2 Chromatin Remodeling and Modification Regulates Eukaryotic Transcription
PEV Mutations
Overview of Chromatin Remodeling and Chromatin Modification
Open and Covered Promoters
Mechanisms of Chromatin Remodeling
Chemical Modifications of Chromatin
Genetic Analysis 13.1
An Example of Inducible Transcriptional Regulation in S. cerevisiae
Facultative Heterochromatin and Developmental Genes
Epigenetic Heritability
lncRNAs and Inactivation of Eutherian Mammalian Female X Chromosomes
Genomic Imprinting
Nucleotide Methylation
13.3 RNA‐Mediated Mechanisms Control Gene Expression
Gene Silencing by Double‐Stranded RNA
Constitutive Heterochromatin Maintenance
The Evolution and Applications of RNAi
Case Study Environmental Epigenetics
Summary 
Preparing for Problem Solving 
Problems
Chapter 14 Analysis of Gene Function by Forward Genetics and Reverse Genetics
14.1 Forward Genetic Screens Identify Genes by Their Mutant Phenotypes
General Design of Forward Genetic Screens
Specific Strategies of Forward Genetic Screens
Analysis of Mutageneses
Identifying Interacting and Redundant Genes Using Modifier Screens
Genetic Analysis 14.1
14.2 Genes Identified by Mutant Phenotype Are Cloned Using Recombinant DNA Technology
Cloning Genes by Complementation
Genome Sequencing to Determine Gene Identification
14.3 Reverse Genetics Investigates Gene Action by Progressing from Gene Identification to Phenotype
Genome Editing
Use of Homologous Recombination in Reverse Genetics
Use of Insertion Mutants in Reverse Genetics
RNA Interference in Gene Activity
Reverse Genetics by TILLING
Genetic Analysis 14.2
14.4 Transgenes Provide a Means of Dissecting Gene Function
Monitoring Gene Expression with Reporter Genes
Enhancer Trapping
Investigating Gene Function with Chimeric Genes
Case Study Reverse Genetics and Genetic Redundancy in Flower Development
Summary
Preparing for Problem Solving 
Problems
APPLICATION C The Genetics of Cancer
C.1 Cancer Is a Somatic Genetic Disease that Is Only Occasionally Inherited
C.2 What Is Cancer and What Are the Characteristics of Cancer?
Progression of Abnormalities
The Hallmarks of Cancer Cells and Malignant Tumors
C.3 The Genetic Basis of Cancer
Single Gene Mutations and Cancer Development
The Genetic Progression of Cancer Development and Cancer Predisposition
Breast and Ovarian Cancer and the Inheritance of Cancer Susceptibility
C.4 Cancer Cell Genome Sequencing and Improvements in Therapy
The Cancer Genome Atlas
Epigenetic Irregularities
Targeted Cancer Therapy
Problems
Chapter 15 Recombinant DNA Technology and Its Applications
15.1 Specific DNA Sequences Are Identified and Manipulated Using Recombinant DNA Technology
Restriction Enzymes
Experimental Insight 15.1
Genetic Analysis 15.1
Molecular Cloning
DNA Libraries
Advances in Altering and Synthesizing DNA Molecules
15.2 Introducing Foreign Genes into Genomes Creates Transgenic Organisms
Expression of Heterologous Genes in Bacterial and Fungal Hosts
Experimental Insight 15.2
Transformation of Plant Genomes by Agrobacterium
Transgenic Animals
Manipulation of DNA Sequences in Vivo
15.3 Gene Therapy Uses Recombinant DNA Technology
Two Forms of Gene Therapy
Somatic Gene Therapy Using ES Cells
Genetic Analysis 15.2
15.4 Cloning of Plants and Animals Produces Genetically Identical Individuals
Case Study Gene Drive Alleles Can Rapidly Spread Through Populations
Summary 
Preparing for Problem Solving
Problems
Chapter 16 Genomics: Genetics from a Whole‐Genome Perspective
16.1 Structural Genomics Provides a Catalog of Genes in a Genome
Whole‐Genome Shotgun Sequencing
Reference Genomes and Resequencing
Metagenomics
Experimental Insight 16.1
16.2 Annotation Ascribes Biological Function to DNA Sequences
Experimental Approaches to Structural Annotation
Computational Approaches to Structural Annotation
Functional Gene Annotation
Research Technique 16.1
Related Genes and Protein Motifs
Variation in Genome Organization among Species
Three Insights from Genome Sequences
16.3 Evolutionary Genomics Traces the History of Genomes
The Tree of Life
Interspecific Genome Comparisons: Gene Content
Research Technique 16.2
Genetic Analysis 16.1
Interspecific Genome Comparisons: Genome Annotation
Interspecific Genome Comparisons: Gene Order
16.4 Functional Genomics Aims to Elucidate Gene Function
Transcriptomics
Other “‐omes” and “‐omics”
Use of Yeast Mutants to Categorize Genes
Genetic Networks
Case Study Genomic Analysis of Insect Guts May Fuel the World
Summary
Preparing for Problem Solving
Problems
Chapter 17 Organellar Inheritance and the Evolution of Organellar Genomes
17.1 Organellar Inheritance Transmits Genes Carried on Organellar Chromosomes
The Discovery of Organellar Inheritance
Homoplasmy and Heteroplasmy
Genome Replication in Organelles
Replicative Segregation of Organelle Genomes
17.2 Modes of Organellar Inheritance Depend on the Organism
Mitochondrial Inheritance in Mammals
Genetic Analysis 17.1
Mating Type and Chloroplast Segregation in Chlamydomonas
Biparental Inheritance in Saccharomyces cerevisiae
Genetic Analysis 17.2
Summary of Organellar Inheritance
17.3 Mitochondria Are the Energy Factories of Eukaryotic Cells
Mitochondrial Genome Structure and Gene Content
Mitochondrial Transcription and Translation
17.4 Chloroplasts Are the Sites of Photosynthesis
Chloroplast Genome Structure and Gene Content
Chloroplast Transcription and Translation
Editing of Chloroplast mRNA
17.5 The Endosymbiosis Theory Explains ‐Mitochondrial and Chloroplast Evolution
Separate Evolution of Mitochondria and Chloroplasts
Experimental Insight 17.1
Continual DNA Transfer from Organelles
Encoding of Organellar Proteins
The Origin of the Eukaryotic Lineage
Secondary and Tertiary Endosymbioses
Case Study Ototoxic Deafness: A Mitochondrial Gene–Environment Interaction
Summary
Preparing for Problem Solving 
Problems
Chapter 18 Developmental Genetics
18.1 Development Is the Building of a Multicellular Organism
Cell Differentiation
Pattern Formation
18.2 Drosophila Development Is a Paradigm for Animal Development
The Developmental Toolkit of Drosophila
Maternal Effects on Pattern Formation
Coordinate Gene Patterning of the Anterior–Posterior Axis
Domains of Gap Gene Expression
Regulation of Pair‐Rule Genes
Specification of Parasegments by Hox Genes
Downstream Targets of Hox Genes
Hox Genes throughout Metazoans
Genetic Analysis 18.1
Stabilization of Cellular Memory by Chromatin Architecture
18.3 Cellular Interactions Specify Cell Fate
Inductive Signaling between Cells
Lateral Inhibition
Cell Death During Development
18.4 “Evolution Behaves Like a Tinkerer”
Evolution through Co‐option
Constraints on Co‐option
18.5 Plants Represent an Independent Experiment in Multicellular Evolution
Development at Meristems
Combinatorial Homeotic Activity in Floral‐Organ Identity
Genetic Analysis 18.2
Case Study Cyclopia and Polydactyly—D‐ifferent Shh Mutations with Distinctive Phenotypes
Summary 
Preparing for Problem Solving 
Problems
Chapter 19 Genetic Analysis of Quantitative Traits
19.1 Quantitative Traits Display Continuous Phenotype Variation
Genetic Potential
Major Gene Effects
Additive Gene Effects
Continuous Phenotypic Variation from Multiple Additive Genes
Allele Segregation in Quantitative Trait Production
Effects of Environmental Factors on Phenotypic Variation
Genetic Analysis 19.1
Threshold Traits
19.2 Quantitative Trait Analysis Is Statistical
Statistical Description of Phenotypic Variation
Partitioning Phenotypic Variance
Partitioning Genetic Variance
19.3 Heritability Measures the Genetic Component of Phenotypic Variation
Genetic Analysis 19.2
Broad Sense Heritability
Twin Studies
Narrow Sense Heritability and Artificial Selection
19.4 Quantitative Trait Loci Are the Genes That Contribute to Quantitative Traits
QTL Mapping Strategies
Identification of QTL Genes
Genome‐Wide Association Studies
Case Study The Genetics of Autism Spectrum Disorders
Summary
Preparing for Problem Solving
Problems
Chapter 20 Population Genetics and Evolution at the Population, Species, and Molecular Levels
20.1 The Hardy–Weinberg Equilibrium Describes the Relationship of Allele and Genotype Frequencies in Populations
Populations and Gene Pools
The Hardy–Weinberg Equilibrium
Determining Autosomal Allele Frequencies in Populations
The Hardy–Weinberg Equilibrium for More than Two Alleles
The Chi‐Square Test of Hardy–Weinberg Predictions
Genetic Analysis 20.1
20.2 Natural Selection Operates through Differential Reproductive Fitness within a Population
Differential Reproductive Fitness and Relative Fitness
Directional Natural Selection
Natural Selection Favoring Heterozygotes
Genetic Analysis 20.2
20.3 Mutation Diversifies Gene Pools
Quantifying the Effects of Mutation on Allele Frequencies
Mutation–Selection Balance
20.4 Gene Flow Occurs by the Movement of Organisms and Genes between Populations
Effects of Gene Flow
Allele Frequency Equilibrium and Equalization
20.5 Genetic Drift Causes Allele Frequency Change by Sampling Error
The Founder Effect
Genetic Bottlenecks
20.6 Inbreeding Alters Genotype Frequencies but Not Allele Frequencies
The Coefficient of Inbreeding
Inbreeding Depression
20.7 New Species Evolve by Reproductive Isolation
Genetic Analysis 20.3
Processes of Speciation
Reproductive Isolation and Speciation
The Molecular Genetics of Evolution in Darwin’s Finches
20.8 Molecular Evolution Changes Genes and Genomes through Time
Vertebrate Steroid Receptor Evolution
Case Study Sickle Cell Disease Evolution and Natural Selection in Humans
Summary 
Preparing for Problem Solving 
Problems
APPLICATION D Human Evolutionary Genetics
D.1 Genome Sequences Reveal Extent of Human Genetic Diversity
SNP Variation in Humans
Variation in CNVs
D.2 Diversity of Extant Humans Suggests an African Origin
Mitochondrial Eve
Y Chromosome Phylogeny
Autosomal Loci
D.3 Comparisons between Great Apes Identify Human‐Specific Traits
Revelations of Great Ape Genomes
Comparing the Human and Chimpanzee Genomes
D.4 Ancient DNA Reveals the Recent History of Our Species
Neandertals
Denisovans
Finding Genes that Make Us Human
D.5 Human Migrations around the Globe
Europe
Australia
D.6 Genetic Evidence for Adaptation to New Environments
Lactose Tolerance
Skin Pigmentation
High Altitude
D.7 Domestication of Plants and Animals: Maize
D.8 The Future
Problems
APPLICATION E Forensic Genetics
E.1 CODIS and Forensic Genetic Analysis
CODIS History and Markers
Electrophoretic Analysis
Forensic Analysis Using CODIS
Paternity Testing
Individual Identification
Remains Identified following the 9‐11 Attack
Identification of the Disappeared in Argentina
E.2 DNA Analysis for Genealogy, Genetic Ancestry, and Genetic Health Risk Assessment
Assessing Genealogical Relationships
Assessing Genetic Ancestry
Genetic Health Risk Assessment
Late‐Onset Alzheimer Disease
Celiac Disease
One Side of the Equation
Problems
References and Additional Reading
Appendix: Answers
Glossary
Credits
Index