Introduction to Genetic Analysis (Loose-Leaf)

by Griffiths, Anthony J.F.; Wessler, Susan R.; Lewontin, Richard C.; Carroll, Sean B.

• ISBN13: 9781429233231
• ISBN10: 1429233230
• Edition: 9th
• Format: Loose-leaf
• Copyright: 2008-12-05
• Publisher: W. H. Freeman

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

Anthony 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.

Table of Contents

Contents
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 organisms

1.6 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 formula

4.8 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 VIRUSES

10.1 Gene Regulation
         The basics of prokaryotic transcriptional regulation: Genetic switches
         A first look at the lac regulatory circuit

10.2 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 mutations

10.3 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 machinery

11.3 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 genomics

16.3 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 mating

17.3 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 traits

18.4 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 Organisms

Appendix A: Genetic Nomenclature
Appendix B: Bioinformatics Resources for Genetics and Genomics
Glossary
Answers to Selected Problems
Index