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Introduction to Genetic Analysis
Introduction to Genetic Analysis
- ISBN 13:
9780716768876
- ISBN 10:
0716768879
- Edition: 9th
- Format: Hardcover
- Copyright: 02/16/2007
- Publisher: W. H. Freeman
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Summary
The author team welcomes a new coauthor, Sean B. Carroll, a recognized leader in the field of evolutionary development, to this new edition ofIntroduction to Genetic Analysis (IGA).The authors' ambitious new plans for this edition focus on showing how genetics is practiced today. In particular, the new edition renews its emphasis on how genetic analysis can be a powerful tool for answering biological questions of all types.Special Preview available.
Author Biography
Read moreAnthony Griffiths is Professor Emeritus at the University of British Columbia, where he taught Introductory Genetics for 35 years. The challenges of teaching that course have led to a lasting interest in how students learn genetics. His research interests center on the developmental genetics of fungi, using the model fungus Neurospora crassa. He also loves to dabble in the population genetics of local plants. Griffiths was President of the Genetics Society of Canada from 1987 to 1989, receiving its Award of Excellence in 1997. He has recently served two terms as Secretary-General of the International Genetics Federation.
Susan Wessler is Regents Professor of Plant Biology at the University of Georgia, where she has been since 1983. She teaches courses in introductory biology and plant genetics to both undergraduates and graduate students. Her interest in innovative teaching methods led to her selection as a Howard Hughes Medical Institute Professor in 2006. She is coauthor of The Mutants of Maize (Cold Spring Harbor Laboratory Press) and of more than 100 research articles. Her scientific interest focuses on the subject of transposable elements and the structure and evolution of genomes. She was elected to membership in the National Academy of Sciences in 1998.
Richard Lewontin is the Alexander Agassiz Research Professor at Harvard University. He has taught genetics, statistics and evolution at North Carolina State University, the University of Rochester, the University of Chicago and Harvard University. His chief area of research is population and evolutionary genetics; he introduced molecular methods into population genetics in 1966. Since then, he has concentrated on the study of genetic variation in proteins and DNA within species. Dr. Lewontin has been President of the Society for the Study of Evolution, the American Society of Naturalists, and the Society for Molecular Biology and Evolution, and for some years, he was coeditor of The American Naturalist.
Sean Carroll is Professor of Molecular Biology and Genetics and Investigator with the Howard Hughes Medical Institute at the University of Wisconsin–Madison, where he teaches genetics and evolutionary developmental biology. Dr. Carroll's research has centered on genes that control body patterns and play major roles in the evolution of animal diversity. He is the author of the several books, including The Making of the Fittest (2006, W.W. Norton) and Endless Forms Most Beautiful: The New Science of Evo Devo (2005, W.W. Norton). The latter was a finalist for the 2005 Los Angeles Times Book Prize (Science and Technology) and the 2006 National Academy of Sciences Communication Award. He is also co-author with Jen Grenier and Scott Weatherbee of the textbook From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design (2nd ed; Blackwell Scientific) and the author or coauthor of more than 100 research articles.
Susan Wessler is Regents Professor of Plant Biology at the University of Georgia, where she has been since 1983. She teaches courses in introductory biology and plant genetics to both undergraduates and graduate students. Her interest in innovative teaching methods led to her selection as a Howard Hughes Medical Institute Professor in 2006. She is coauthor of The Mutants of Maize (Cold Spring Harbor Laboratory Press) and of more than 100 research articles. Her scientific interest focuses on the subject of transposable elements and the structure and evolution of genomes. She was elected to membership in the National Academy of Sciences in 1998.
Richard Lewontin is the Alexander Agassiz Research Professor at Harvard University. He has taught genetics, statistics and evolution at North Carolina State University, the University of Rochester, the University of Chicago and Harvard University. His chief area of research is population and evolutionary genetics; he introduced molecular methods into population genetics in 1966. Since then, he has concentrated on the study of genetic variation in proteins and DNA within species. Dr. Lewontin has been President of the Society for the Study of Evolution, the American Society of Naturalists, and the Society for Molecular Biology and Evolution, and for some years, he was coeditor of The American Naturalist.
Sean Carroll is Professor of Molecular Biology and Genetics and Investigator with the Howard Hughes Medical Institute at the University of Wisconsin–Madison, where he teaches genetics and evolutionary developmental biology. Dr. Carroll's research has centered on genes that control body patterns and play major roles in the evolution of animal diversity. He is the author of the several books, including The Making of the Fittest (2006, W.W. Norton) and Endless Forms Most Beautiful: The New Science of Evo Devo (2005, W.W. Norton). The latter was a finalist for the 2005 Los Angeles Times Book Prize (Science and Technology) and the 2006 National Academy of Sciences Communication Award. He is also co-author with Jen Grenier and Scott Weatherbee of the textbook From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design (2nd ed; Blackwell Scientific) and the author or coauthor of more than 100 research articles.
Table of Contents
Read moreContents
Preface
TRANSMISSION GENETICS
CHAPTER 1 THE GENETIC APPROACH TO BIOLOGY
1.1 Genetics and the Questions of Biology
1.2 The Molecular Basis of Genetic Information
Specifying the amino acid sequence of a protein
Gene regulation
1.3 The Program of Genetic Investigation
Starting with variation: Forward genetics
Starting with DNA: Reverse genetics
1.4 Methodologies Used in Genetics
Detecting specific molecules of DNA, RNA, and protein
1.5 Model Organisms
Lessons from the first model organisms
The need for a variety of model organisms1.6 Genes, the Environment, and the Organism
Model I: Genetic determination
Model II: Environmental determination
Model III: Genotype-environment interaction
The use of genotype and phenotype
Developmental noise
Three levels of development
CHAPTER 2 SINGLE-GENE INHERITANCE
2.1 Genes and Chromosomes
2.2 Single-Gene Inheritance Patterns
Mendel’s law of equal segregation
2.3 The Chromosomal Basis of Single-Gene Inheritance Patterns
Single-gene inheritance in haploids
The molecular basis of single-gene segregation and expression
2.4 Identifying Genes by Observing Segregation Ratios
Discovering a gene active in the development of flower color
Discovering a gene for wing development
Discovering a gene for spore production
The results of gene discovery
Forward genetics
Predicting progeny proportions or parental genotypes by applying the principles of single-gene influence
2.5 Sex-Linked Single-Gene Inheritance Patterns
Sex-linked patterns of inheritance
X-linked inheritance
2.6 Human Pedigree Analysis
Autosomal recessive disorders
Autosomal dominant disorders
Autosomal polymorphisms
X-linked recessive disorders
X-linked dominant disorders
Y-linked inheritance
Calculating risks in pedigree analysis
CHAPTER 3 INDEPENDENT ASSORTMENT OF GENES
3.1 Mendel’s Law of Independent Assortment
3.2 Working with Independent Assortment
Predicting progeny ratios
Using the chi-square test on monohybrid and dihybrid ratios
Synthesizing pure lines
Hybrid vigor
3.3 The Chromosomal Basis of Independent Assortment
Independent assortment in diploid organisms
Independent assortment in haploid organisms
Independent assortment of combinations of autosomal and X-linked genes
Recombination
3.4 Polygenic Inheritance
3.5 Organelle Genes: Inheritance Independent of the Nucleus
Patterns of inheritance in organelles
Cytoplasmic segregation
Cytoplasmic mutations in humans
CHAPTER 4 MAPPING EUKARYOTE CHROMOSOMES BY RECOMBINATION
4.1 Diagnostics of Linkage
Using recombinant frequency to recognize linkage
How crossovers produce recombinants for linked genes
Linkage symbolism and terminology
Evidence that crossing over is a breakage-and-rejoining process
Evidence that crossing over takes place at the four-chromatid stage
Multiple crossovers can include more than two chromatids
4.2 Mapping by Recombinant Frequency
Map units
Three point testcross
Deducing gene order by inspection
Interference
Using ratios as diagnostics
4.3 Mapping with Molecular Markers
Single nucleotide polymorphisms
Mapping by using SNP haplotypes
Simple sequence length polymorphisms
4.4 Centromere Mapping with Linear Tetrads
4.5 Using the Chi-Square Test for Testing Linkage Analysis
4.6 Using Lod Scores to Assess Linkage in Human Pedigrees
4.7 Accounting for Unseen Multiple Crossovers
A mapping function
The Perkins formula4.8 Using Recombination-Based Maps in Conjunction with Physical Maps
CHAPTER 5 THE GENETICS OF BACTERIA AND THEIR VIRUSES
5.1 Working with Microorganisms
5.2 Bacterial Conjugation
Discovery of conjugation
Discovery of the fertility factor (F)
Hfr strains
Mapping of bacterial chromosomes
F plasmids that carry genomic fragments
R plasmids
5.3 Bacterial Transformation
Chromosome mapping using transformation
5.4 Bacteriophage Genetics
Infection of bacteria by phages
Mapping phage chromosomes by using phage crosses
5.5 Transduction
Discovery of transduction
Generalized transduction
Specialized transduction
Mechanism of specialized transduction
5.6 Physical Maps and Linkage Maps Compared
FROM DNA TO PHENOTYPE
CHAPTER 6 GENE INTERACTION
6.1 Interactions Between the Alleles of a Single Gene: Variations on Dominance
Complete dominance and recessiveness
Incomplete dominance
Codominance
Recessive lethal alleles
6.2 Interaction of Genes in Pathways
Biosynthetic pathways in Neurospora
Gene interaction in other types of pathways
6.3 Inferring Gene Interactions
Defining the set of genes by using the complementation test
Analyzing double mutants of random mutations
6.4 Penetrance and Expressivity
CHAPTER 7 DNA: STRUCTURE AND REPLICATION
7.1 DNA: The Genetic Material
Discovery of transformation
Hershey-Chase experiment
7.2 The DNA Structure
DNA structure before Watson and Crick
The double helix
7.3 Semiconservative Replication
Meselson-Stahl experiment
The replication fork
DNA polymerases
7.4 Overview of DNA Replication
7.5 The Replisome: A Remarkable Replication Machine
Unwinding the double helix
Assembling the replisome: replication initiation
7.6 Replication in Eukaryotic Organisms
The eukaryotic replisome
Eukaryotic origins of replication
DNA replication and the yeast cell cycle
Replication origins in higher eukaryotes
7.7 Telomeres and Telomerase: Replication Termination
Telomeres, cancer, and aging
CHAPTER 8 RNA: TRANSCRIPTION AND PROCESSING
8.1 RNA
Early experiments suggest an RNA intermediate
Properties of RNA
Classes of RNA
8.2 Transcription
Overview: DNA as transcription template
Stages of transcription
8.3 Transcription in eukaryotes
Transcription initiation in eukaryotes
Elongation, termination, and pre-mRNA processing in eukaryotes
8.4 Functional RNAs
Small nuclear RNAs (snRNAs): The mechanism of exon splicing
Self-splicing introns and the RNA world
Small interfering RNAs (siRNAs)
CHAPTER 9 PROTEINS AND THEIR SYNTHESIS
9.1 Protein Structure
9.2 Colinearity of gene and protein
9.3 The Genetic Code
Overlapping versus nonoverlapping codes
Number of letters in the codon
Use of suppressors to demonstrate a triplet code
Degeneracy of the genetic code
Cracking the code
Stop codons
9.4 tRNA: The Adapter
Codon translation by tRNA
Degeneracy revisited
9.5 Ribosomes
Ribosome features
Translation, initiation, elongation, and termination
Nonsense suppressor mutations
9.6 The Proteome
Alternative splicing generates protein isoforms
Posttranslational events
CHAPTER 10 REGULATION OF GENE EXPRESSION IN BACTERIA AND THEIR VIRUSES10.1 Gene Regulation
The basics of prokaryotic transcriptional regulation: Genetic switches
A first look at the lac regulatory circuit10.2 Discovery of the lac System: Negative Control
Genes controlled together
Genetic evidence for the operator and repressor
Genetic evidence for allostery
Genetic analysis of the lac promoter
Molecular characterization of the lac repressor and the lac operator
Polar mutations10.3 Catabolic Repression of the lac Operon: Positive Control
The basics of catabolite repression of the lac operon: Choosing the best sugar to metabolize
The structure of target DNA sites
A summary of the lac operon
10.4 Dual Positive and Negative Control: The Arabinose Operon
10.5 Metabolic Pathways and Additional Levels of Regulation: Attenuation
Transcription of the trp operon is regulated at two steps
10.6 Bacteriophage Life Cycles: More Regulators, Complex Operons
Molecular anatomy of the genetic switch
Sequence-specific binding of regulatory proteins to DNA
10.7 Alternative Sigma Factors Regulate Large Sets of Genes
CHAPTER 11 REGULATION OF GENE EXPRESSION IN EUKARYOTES
11.1 Transcriptional Regulation in Eukaryotes: An Overview
11.2 Lessons from Yeast: the GAL System
Gal4 regulates multiple genes through upstream activation sequences
The Gal4 protein has separable DNA-binding and activation domains
Gal4 activity is physiologically regulated
Gal4 functions in most eukaryotes
Activators recruit the transcriptional machinery11.3 Dynamic Chromatin and Eukaryotic Gene Regulation
Chromatin-remodeling proteins and gene activation
Histones and chromatin remodeling
11.4 Enhancers: Cooperative Interactions, Combinatorial Control, and Chromatin Remodeling
The b-interferon enhanceosome
The control of yeast mating type: Combinatorial interactions
DNA-binding proteins combinatorially regulate the expression of cell-type-specific genes
Enhancer-blocking insulators
11.5 Genomic Imprinting
But what about Dolly and other cloned mammals?
11.6 Chromatin Domains and Their Inheritance
Mating-type switching and gene silencing
Heterochromatin and euchromatin compared
Position-effect variegation in Drosophila reveals genomic neighborhoods
Genetic analysis of PEV reveals proteins necessary for heterochromatin formation
Silencing an entire chromosome: X-chromosome inactivation
The inheritance of epigenetic marks and chromatin structure
CHAPTER 12 THE GENETIC CONTROL OF DEVELOPMENT
12.1 The Genetic Approach to Development
12.2 The Genetic Toolkit for Drosophila Development
Classification of genes by developmental function
Homeotic genes and segmental identity
Organization and expression of Hox genes
The homeobox
Clusters of Hox genes control development in most animals
12.3 Defining the Entire Toolkit
The anteroposterior and dorsoventral axes
Expression of toolkit genes
12.4 Spatial Regulation of Gene Expression in Development
Maternal gradients and gene activation
Drawing stripes: Integration of gap-protein inputs
Making segments different: Integration of Hox inputs
12.5 Posttranscriptional Regulation of Gene Expression in Development
RNA splicing and sex determination in Drosophila
Regulation of mRNA translation and cell lineage in C. elegans
Translational control in the early embryo
miRNA control of developmental timing in C. elegans and other species
12.6 The Many Roles of Individual Toolkit Genes
From flies to fingers, feathers, and floor plates
12.7 Development and Disease
Polydactyly
Holoprosencephaly
Cancer as a developmental disease
CHAPTER 13 GENOMES AND GENOMICS
13.1 The Genomics Revolution
13.2 Creating the Sequence Map of a Genome
Turning sequence reads into a sequence map
Establishing a genomic library of clones
Sequencing a simple genome by using the whole-genome shotgun approach
Using the whole-genome shotgun approach to create a draft sequence of a complex genome
Using the ordered-clone approach to sequence a complex genome
Filling sequence gaps
13.3 Bioinformatics: Meaning from Genomic Sequence
The nature of the information content of DNA
Deducing the protein-encoding genes from genomic sequence
13.4 The Structure of the Human Genome
13.5 Comparative Genomics
Of mice and humans
Comparative genomics of chimpanzees and humans
Conserved and ultraconserved noncoding elements
Comparative genomics of non-pathogenic and pathogenic E. coli
13.6 Functional Genomics and Reverse Genetics
Ome, Sweet Ome
Reverse genetics
MUTATION, VARIATION, AND EVOLUTION
CHAPTER 14 THE DYNAMIC GENOME
14.1 Discovery of transposable elements in maize
McClintock’s experiments: the Ds element
Autonomous and nonautomous elements
Transposable elements: only in maize?
14.2 Transposable elements in bacteria
Bacterial insertion sequences
Prokaryotic transposons
Mechanism of transposition
14.3 Transposable elements in eukaryotes
Class I: retrotransposons
DNA transposons
Utility of DNA transposons for gene discovery
14.4 The dynamic genome: more transposable elements than ever imagined
Large genomes are largely transposable elements
Transposable elements in the human genome
The grasses: LTR retrotransposons thrive in large genomes
Safe havens
CHAPTER 15 MUTATION, REPAIR, AND RECOMBINATION
15.1 Phenotypic consequences of DNA alterations
Types of point mutation
The molecular consequences of point mutations in a coding region
The molecular consequences of point mutations in a noncoding region
15.2 The Molecular Basis of Spontaneous Mutations
Luria and Delbrück fluctuation test
Mechanisms of spontaneous mutations
Spontaneous mutations in humans—trinucleotide repeat diseases
15.3 The Molecular Basis of Induced Mutations
Mechanisms of mutagenesis
The Ames test: Evaluating mutagens in our environment
15.4 Cancer: An Important Phenotypic Consequence of Mutations
How cancer cells differ from normal cells
Mutations in cancer cells
15.5 Biological Repair Mechanisms
Direct reversal of damaged DNA
Homology-dependent repair systems
Postreplication repair: mismatch repair
Error-prone repair: Translesion DNA synthesis
Repair of double-strand breaks
15.6 The Mechanism of Meiotic Crossing-Over
Programmed double-strand breaks initiate meiotic recombination
Genetic analysis of tetrads provides clues to the mechanism of recombination
The double-strand break model for meiotic recombination
CHAPTER 16 LARGE-SCALE CHROMOSOMAL CHANGES
16.1 Changes in Chromosome Number
Aberrant euploidy
Aneuploidy
The concept of gene balance
16.2 Changes in Chromosome Structure
Deletions
Duplications
Inversions
Reciprocal translocations
Robertsonian translocations
Applications of inversions and translocations
Rearrangements and cancer
Identifying chromosome mutations by genomics16.3 Overall Incidence of Human Chromosome Mutations
CHAPTER 17 POPULATION GENETICS
17.1 Variation and Its Modulation
Observations of variation
Protein polymorphisms
DNA structure and sequence polymorphism
17.2 Effect of Sexual Reproduction on Variation
Meiotic segregation and genetic equilibrium
Heterozygosity
Random mating
Inbreeding and assertive mating17.3 Sources of Variation
Variation from mutation
Variation from recombination
Variation from migration
17.4 Selection
Two forms of selection
Measuring fitness differences
How selection works
Rate of change in gene frequency
17.5 Balanced Polymorphism
Overdominance and underdominance
Balance between mutation and selection
17.6 Random Events
CHAPTER 18 QUANTITATIVE GENETICS
18.1 Genes and Quantitative Traits
18.2 Some Basic Statistical Notions
Statistical distributions
Statistical measures
18.3 Genotypes and Phenotypic Distribution
The critical difference between quantitative and Mendelian traits
Gene number and quantitative traits18.4 Norm of Reaction and Phenotypic Distribution
18.5 Determining Norms of Reaction
Domesticated plants and animals
Studies of natural populations
Results of norm-of-reaction studies
18.6 The Heritability of a Quantitative Character
Familiarity and heritability
Phenotypic similarity between relatives
18.7 Quantifying Heritability
Methods of estimating H2
The meaning of H2
Narrow heritability
Estimating the components of genetic variance
Artificial selection
The use of H2 in breeding
18.8 Locating Genes
Marker-gene segregation
Quantitative linkage analysis
CHAPTER 19 EVOLUTIONARY GENETICS
19.1 Darwinian Evolution
19.2 A Synthesis of Forces: Variation and Divergence of Populations
19.3 Multiple Adaptive Peaks
Exploration of adaptive peaks
19.4 Genetic Variation
Heritability of variation
Variation within and between populations
19.5 Mutation and Molecular Evolution
The signature of purifying selection on DNA
19.6 Relating Genetic to Functional Change: Protein Evolution
The signature of positive selection on DNA sequences
Morphological evolution
Gene inactivation
19.7 Regulatory Evolution
Regulatory evolution in humans
19.8 The Origin of New Genes
Polyploidy
Duplications
Imported DNA
19.9 Genetic Evidence of Common Ancestry in Evolution
Comparing the proteomes among distant species
Comparing the proteomes among near neighbors: Human-mouse comparative genomics
19.10 The Process of Speciation
Genetics of species isolation
TECHNIQUES
CHAPTER 20 GENE ISOLATION AND MANIPULATION
20.1 Mutant screens
20.2 Generating Recombinant Molecules
Type of donor DNA
Cutting genomic DNA
Attaching vector DNA and vector DNA
Amplification inside a bacterial cell
Entry of recombinant molecules into the bacterial cell
Recovery of amplified recombinant molecules
Making genomic and cDNA libraries
Finding a specific clone of interest
Determining the base sequence of a DNA segment
20.3 DNA Amplification in Vitro: the Polymerase Chain Reaction
20.4 Zeroing in on the Gene for Alkaptonuria: Another Case Study
20.5 Detecting Human Disease Alleles: Molecular Genetic Diagnostics
Diagnosing mutations on the basis of restriction-site differences
Diagnosing mutations by probe hybridization
Diagnosing with PCR tests
20.6 Genetic Engineering
Genetic engineering in Saccharomyces cerevisiae
Genetic engineering in plants
Genetic engineering in animals
Human gene therapy
A Brief Guide to Model OrganismsAppendix A: Genetic Nomenclature
Appendix B: Bioinformatics Resources for Genetics and Genomics
Glossary
Answers to Selected Problems
Index
Preface
TRANSMISSION GENETICS
CHAPTER 1 THE GENETIC APPROACH TO BIOLOGY
1.1 Genetics and the Questions of Biology
1.2 The Molecular Basis of Genetic Information
Specifying the amino acid sequence of a protein
Gene regulation
1.3 The Program of Genetic Investigation
Starting with variation: Forward genetics
Starting with DNA: Reverse genetics
1.4 Methodologies Used in Genetics
Detecting specific molecules of DNA, RNA, and protein
1.5 Model Organisms
Lessons from the first model organisms
The need for a variety of model organisms1.6 Genes, the Environment, and the Organism
Model I: Genetic determination
Model II: Environmental determination
Model III: Genotype-environment interaction
The use of genotype and phenotype
Developmental noise
Three levels of development
CHAPTER 2 SINGLE-GENE INHERITANCE
2.1 Genes and Chromosomes
2.2 Single-Gene Inheritance Patterns
Mendel’s law of equal segregation
2.3 The Chromosomal Basis of Single-Gene Inheritance Patterns
Single-gene inheritance in haploids
The molecular basis of single-gene segregation and expression
2.4 Identifying Genes by Observing Segregation Ratios
Discovering a gene active in the development of flower color
Discovering a gene for wing development
Discovering a gene for spore production
The results of gene discovery
Forward genetics
Predicting progeny proportions or parental genotypes by applying the principles of single-gene influence
2.5 Sex-Linked Single-Gene Inheritance Patterns
Sex-linked patterns of inheritance
X-linked inheritance
2.6 Human Pedigree Analysis
Autosomal recessive disorders
Autosomal dominant disorders
Autosomal polymorphisms
X-linked recessive disorders
X-linked dominant disorders
Y-linked inheritance
Calculating risks in pedigree analysis
CHAPTER 3 INDEPENDENT ASSORTMENT OF GENES
3.1 Mendel’s Law of Independent Assortment
3.2 Working with Independent Assortment
Predicting progeny ratios
Using the chi-square test on monohybrid and dihybrid ratios
Synthesizing pure lines
Hybrid vigor
3.3 The Chromosomal Basis of Independent Assortment
Independent assortment in diploid organisms
Independent assortment in haploid organisms
Independent assortment of combinations of autosomal and X-linked genes
Recombination
3.4 Polygenic Inheritance
3.5 Organelle Genes: Inheritance Independent of the Nucleus
Patterns of inheritance in organelles
Cytoplasmic segregation
Cytoplasmic mutations in humans
CHAPTER 4 MAPPING EUKARYOTE CHROMOSOMES BY RECOMBINATION
4.1 Diagnostics of Linkage
Using recombinant frequency to recognize linkage
How crossovers produce recombinants for linked genes
Linkage symbolism and terminology
Evidence that crossing over is a breakage-and-rejoining process
Evidence that crossing over takes place at the four-chromatid stage
Multiple crossovers can include more than two chromatids
4.2 Mapping by Recombinant Frequency
Map units
Three point testcross
Deducing gene order by inspection
Interference
Using ratios as diagnostics
4.3 Mapping with Molecular Markers
Single nucleotide polymorphisms
Mapping by using SNP haplotypes
Simple sequence length polymorphisms
4.4 Centromere Mapping with Linear Tetrads
4.5 Using the Chi-Square Test for Testing Linkage Analysis
4.6 Using Lod Scores to Assess Linkage in Human Pedigrees
4.7 Accounting for Unseen Multiple Crossovers
A mapping function
The Perkins formula4.8 Using Recombination-Based Maps in Conjunction with Physical Maps
CHAPTER 5 THE GENETICS OF BACTERIA AND THEIR VIRUSES
5.1 Working with Microorganisms
5.2 Bacterial Conjugation
Discovery of conjugation
Discovery of the fertility factor (F)
Hfr strains
Mapping of bacterial chromosomes
F plasmids that carry genomic fragments
R plasmids
5.3 Bacterial Transformation
Chromosome mapping using transformation
5.4 Bacteriophage Genetics
Infection of bacteria by phages
Mapping phage chromosomes by using phage crosses
5.5 Transduction
Discovery of transduction
Generalized transduction
Specialized transduction
Mechanism of specialized transduction
5.6 Physical Maps and Linkage Maps Compared
FROM DNA TO PHENOTYPE
CHAPTER 6 GENE INTERACTION
6.1 Interactions Between the Alleles of a Single Gene: Variations on Dominance
Complete dominance and recessiveness
Incomplete dominance
Codominance
Recessive lethal alleles
6.2 Interaction of Genes in Pathways
Biosynthetic pathways in Neurospora
Gene interaction in other types of pathways
6.3 Inferring Gene Interactions
Defining the set of genes by using the complementation test
Analyzing double mutants of random mutations
6.4 Penetrance and Expressivity
CHAPTER 7 DNA: STRUCTURE AND REPLICATION
7.1 DNA: The Genetic Material
Discovery of transformation
Hershey-Chase experiment
7.2 The DNA Structure
DNA structure before Watson and Crick
The double helix
7.3 Semiconservative Replication
Meselson-Stahl experiment
The replication fork
DNA polymerases
7.4 Overview of DNA Replication
7.5 The Replisome: A Remarkable Replication Machine
Unwinding the double helix
Assembling the replisome: replication initiation
7.6 Replication in Eukaryotic Organisms
The eukaryotic replisome
Eukaryotic origins of replication
DNA replication and the yeast cell cycle
Replication origins in higher eukaryotes
7.7 Telomeres and Telomerase: Replication Termination
Telomeres, cancer, and aging
CHAPTER 8 RNA: TRANSCRIPTION AND PROCESSING
8.1 RNA
Early experiments suggest an RNA intermediate
Properties of RNA
Classes of RNA
8.2 Transcription
Overview: DNA as transcription template
Stages of transcription
8.3 Transcription in eukaryotes
Transcription initiation in eukaryotes
Elongation, termination, and pre-mRNA processing in eukaryotes
8.4 Functional RNAs
Small nuclear RNAs (snRNAs): The mechanism of exon splicing
Self-splicing introns and the RNA world
Small interfering RNAs (siRNAs)
CHAPTER 9 PROTEINS AND THEIR SYNTHESIS
9.1 Protein Structure
9.2 Colinearity of gene and protein
9.3 The Genetic Code
Overlapping versus nonoverlapping codes
Number of letters in the codon
Use of suppressors to demonstrate a triplet code
Degeneracy of the genetic code
Cracking the code
Stop codons
9.4 tRNA: The Adapter
Codon translation by tRNA
Degeneracy revisited
9.5 Ribosomes
Ribosome features
Translation, initiation, elongation, and termination
Nonsense suppressor mutations
9.6 The Proteome
Alternative splicing generates protein isoforms
Posttranslational events
CHAPTER 10 REGULATION OF GENE EXPRESSION IN BACTERIA AND THEIR VIRUSES10.1 Gene Regulation
The basics of prokaryotic transcriptional regulation: Genetic switches
A first look at the lac regulatory circuit10.2 Discovery of the lac System: Negative Control
Genes controlled together
Genetic evidence for the operator and repressor
Genetic evidence for allostery
Genetic analysis of the lac promoter
Molecular characterization of the lac repressor and the lac operator
Polar mutations10.3 Catabolic Repression of the lac Operon: Positive Control
The basics of catabolite repression of the lac operon: Choosing the best sugar to metabolize
The structure of target DNA sites
A summary of the lac operon
10.4 Dual Positive and Negative Control: The Arabinose Operon
10.5 Metabolic Pathways and Additional Levels of Regulation: Attenuation
Transcription of the trp operon is regulated at two steps
10.6 Bacteriophage Life Cycles: More Regulators, Complex Operons
Molecular anatomy of the genetic switch
Sequence-specific binding of regulatory proteins to DNA
10.7 Alternative Sigma Factors Regulate Large Sets of Genes
CHAPTER 11 REGULATION OF GENE EXPRESSION IN EUKARYOTES
11.1 Transcriptional Regulation in Eukaryotes: An Overview
11.2 Lessons from Yeast: the GAL System
Gal4 regulates multiple genes through upstream activation sequences
The Gal4 protein has separable DNA-binding and activation domains
Gal4 activity is physiologically regulated
Gal4 functions in most eukaryotes
Activators recruit the transcriptional machinery11.3 Dynamic Chromatin and Eukaryotic Gene Regulation
Chromatin-remodeling proteins and gene activation
Histones and chromatin remodeling
11.4 Enhancers: Cooperative Interactions, Combinatorial Control, and Chromatin Remodeling
The b-interferon enhanceosome
The control of yeast mating type: Combinatorial interactions
DNA-binding proteins combinatorially regulate the expression of cell-type-specific genes
Enhancer-blocking insulators
11.5 Genomic Imprinting
But what about Dolly and other cloned mammals?
11.6 Chromatin Domains and Their Inheritance
Mating-type switching and gene silencing
Heterochromatin and euchromatin compared
Position-effect variegation in Drosophila reveals genomic neighborhoods
Genetic analysis of PEV reveals proteins necessary for heterochromatin formation
Silencing an entire chromosome: X-chromosome inactivation
The inheritance of epigenetic marks and chromatin structure
CHAPTER 12 THE GENETIC CONTROL OF DEVELOPMENT
12.1 The Genetic Approach to Development
12.2 The Genetic Toolkit for Drosophila Development
Classification of genes by developmental function
Homeotic genes and segmental identity
Organization and expression of Hox genes
The homeobox
Clusters of Hox genes control development in most animals
12.3 Defining the Entire Toolkit
The anteroposterior and dorsoventral axes
Expression of toolkit genes
12.4 Spatial Regulation of Gene Expression in Development
Maternal gradients and gene activation
Drawing stripes: Integration of gap-protein inputs
Making segments different: Integration of Hox inputs
12.5 Posttranscriptional Regulation of Gene Expression in Development
RNA splicing and sex determination in Drosophila
Regulation of mRNA translation and cell lineage in C. elegans
Translational control in the early embryo
miRNA control of developmental timing in C. elegans and other species
12.6 The Many Roles of Individual Toolkit Genes
From flies to fingers, feathers, and floor plates
12.7 Development and Disease
Polydactyly
Holoprosencephaly
Cancer as a developmental disease
CHAPTER 13 GENOMES AND GENOMICS
13.1 The Genomics Revolution
13.2 Creating the Sequence Map of a Genome
Turning sequence reads into a sequence map
Establishing a genomic library of clones
Sequencing a simple genome by using the whole-genome shotgun approach
Using the whole-genome shotgun approach to create a draft sequence of a complex genome
Using the ordered-clone approach to sequence a complex genome
Filling sequence gaps
13.3 Bioinformatics: Meaning from Genomic Sequence
The nature of the information content of DNA
Deducing the protein-encoding genes from genomic sequence
13.4 The Structure of the Human Genome
13.5 Comparative Genomics
Of mice and humans
Comparative genomics of chimpanzees and humans
Conserved and ultraconserved noncoding elements
Comparative genomics of non-pathogenic and pathogenic E. coli
13.6 Functional Genomics and Reverse Genetics
Ome, Sweet Ome
Reverse genetics
MUTATION, VARIATION, AND EVOLUTION
CHAPTER 14 THE DYNAMIC GENOME
14.1 Discovery of transposable elements in maize
McClintock’s experiments: the Ds element
Autonomous and nonautomous elements
Transposable elements: only in maize?
14.2 Transposable elements in bacteria
Bacterial insertion sequences
Prokaryotic transposons
Mechanism of transposition
14.3 Transposable elements in eukaryotes
Class I: retrotransposons
DNA transposons
Utility of DNA transposons for gene discovery
14.4 The dynamic genome: more transposable elements than ever imagined
Large genomes are largely transposable elements
Transposable elements in the human genome
The grasses: LTR retrotransposons thrive in large genomes
Safe havens
CHAPTER 15 MUTATION, REPAIR, AND RECOMBINATION
15.1 Phenotypic consequences of DNA alterations
Types of point mutation
The molecular consequences of point mutations in a coding region
The molecular consequences of point mutations in a noncoding region
15.2 The Molecular Basis of Spontaneous Mutations
Luria and Delbrück fluctuation test
Mechanisms of spontaneous mutations
Spontaneous mutations in humans—trinucleotide repeat diseases
15.3 The Molecular Basis of Induced Mutations
Mechanisms of mutagenesis
The Ames test: Evaluating mutagens in our environment
15.4 Cancer: An Important Phenotypic Consequence of Mutations
How cancer cells differ from normal cells
Mutations in cancer cells
15.5 Biological Repair Mechanisms
Direct reversal of damaged DNA
Homology-dependent repair systems
Postreplication repair: mismatch repair
Error-prone repair: Translesion DNA synthesis
Repair of double-strand breaks
15.6 The Mechanism of Meiotic Crossing-Over
Programmed double-strand breaks initiate meiotic recombination
Genetic analysis of tetrads provides clues to the mechanism of recombination
The double-strand break model for meiotic recombination
CHAPTER 16 LARGE-SCALE CHROMOSOMAL CHANGES
16.1 Changes in Chromosome Number
Aberrant euploidy
Aneuploidy
The concept of gene balance
16.2 Changes in Chromosome Structure
Deletions
Duplications
Inversions
Reciprocal translocations
Robertsonian translocations
Applications of inversions and translocations
Rearrangements and cancer
Identifying chromosome mutations by genomics16.3 Overall Incidence of Human Chromosome Mutations
CHAPTER 17 POPULATION GENETICS
17.1 Variation and Its Modulation
Observations of variation
Protein polymorphisms
DNA structure and sequence polymorphism
17.2 Effect of Sexual Reproduction on Variation
Meiotic segregation and genetic equilibrium
Heterozygosity
Random mating
Inbreeding and assertive mating17.3 Sources of Variation
Variation from mutation
Variation from recombination
Variation from migration
17.4 Selection
Two forms of selection
Measuring fitness differences
How selection works
Rate of change in gene frequency
17.5 Balanced Polymorphism
Overdominance and underdominance
Balance between mutation and selection
17.6 Random Events
CHAPTER 18 QUANTITATIVE GENETICS
18.1 Genes and Quantitative Traits
18.2 Some Basic Statistical Notions
Statistical distributions
Statistical measures
18.3 Genotypes and Phenotypic Distribution
The critical difference between quantitative and Mendelian traits
Gene number and quantitative traits18.4 Norm of Reaction and Phenotypic Distribution
18.5 Determining Norms of Reaction
Domesticated plants and animals
Studies of natural populations
Results of norm-of-reaction studies
18.6 The Heritability of a Quantitative Character
Familiarity and heritability
Phenotypic similarity between relatives
18.7 Quantifying Heritability
Methods of estimating H2
The meaning of H2
Narrow heritability
Estimating the components of genetic variance
Artificial selection
The use of H2 in breeding
18.8 Locating Genes
Marker-gene segregation
Quantitative linkage analysis
CHAPTER 19 EVOLUTIONARY GENETICS
19.1 Darwinian Evolution
19.2 A Synthesis of Forces: Variation and Divergence of Populations
19.3 Multiple Adaptive Peaks
Exploration of adaptive peaks
19.4 Genetic Variation
Heritability of variation
Variation within and between populations
19.5 Mutation and Molecular Evolution
The signature of purifying selection on DNA
19.6 Relating Genetic to Functional Change: Protein Evolution
The signature of positive selection on DNA sequences
Morphological evolution
Gene inactivation
19.7 Regulatory Evolution
Regulatory evolution in humans
19.8 The Origin of New Genes
Polyploidy
Duplications
Imported DNA
19.9 Genetic Evidence of Common Ancestry in Evolution
Comparing the proteomes among distant species
Comparing the proteomes among near neighbors: Human-mouse comparative genomics
19.10 The Process of Speciation
Genetics of species isolation
TECHNIQUES
CHAPTER 20 GENE ISOLATION AND MANIPULATION
20.1 Mutant screens
20.2 Generating Recombinant Molecules
Type of donor DNA
Cutting genomic DNA
Attaching vector DNA and vector DNA
Amplification inside a bacterial cell
Entry of recombinant molecules into the bacterial cell
Recovery of amplified recombinant molecules
Making genomic and cDNA libraries
Finding a specific clone of interest
Determining the base sequence of a DNA segment
20.3 DNA Amplification in Vitro: the Polymerase Chain Reaction
20.4 Zeroing in on the Gene for Alkaptonuria: Another Case Study
20.5 Detecting Human Disease Alleles: Molecular Genetic Diagnostics
Diagnosing mutations on the basis of restriction-site differences
Diagnosing mutations by probe hybridization
Diagnosing with PCR tests
20.6 Genetic Engineering
Genetic engineering in Saccharomyces cerevisiae
Genetic engineering in plants
Genetic engineering in animals
Human gene therapy
A Brief Guide to Model OrganismsAppendix A: Genetic Nomenclature
Appendix B: Bioinformatics Resources for Genetics and Genomics
Glossary
Answers to Selected Problems
Index
Supplemental Materials
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