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William S. Klug • Michael R. Cummings Charlotte A. Spencer • Michael A. Palladino
Concepts of Genetics elevenTh edITIon
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Concepts of Genetics PDF eBook, Global Edition
Table of Contents
Cover
Title Page
Copyright Page
Dedication
About the Authors
Brief Contents
Explore Cutting Edge Topics
Explore Classic and Modern Approaches
Learn and Practice Problem Solving
Succeed with MasteringGenetics
Contents
Preface
1. Introduction to Genetics1.1. Genetics Has a Rich and Interesting History
1600–1850: The Dawn of Modern Biology
Charles Darwin and Evolution
1.2. Genetics Progressed from Mendel to DNA in Less Than a CenturyMendel’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?
1.3. Discovery of the Double Helix Launched the Era of Molecular GeneticsThe Structure of DNA and RNA
Gene Expression: From DNA to Phenotype
Proteins and Biological Function
Linking Genotype to Phenotype: Sickle-Cell Anemia
1.4. Development of Recombinant DNA Technology Began the Era of DNA Cloning
1.5. The Impact of Biotechnology is Continually ExpandingPlants, Animals, and the Food Supply
Biotechnology in Genetics and Medicine
1.6. Genomics, Proteomics, and Bioinformatics are New and Expanding FieldsModern Approaches to Understanding Gene Function
1.7. Genetic Studies Rely on the Use of Model OrganismsThe Modern Set of Genetic Model Organisms
Model Organisms and Human Diseases
1.8. We Live in the Age of Genetics
Table of Contents
The Nobel Prize and Genetics
Genetics and Society
The Scientific and Ethical Implications of Modern Genetics
Internet Resources for Learning About Genomics, Bioinformatics, and Proteomics
Summary Points
Case Study: Extending Essential Ideas of Genetics Beyond the Classroom
Problems and Discussion Questions
2. Mitosis and Meiosis2.1. 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 CellsInterphase 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 Cellsand 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 Sexual Reproduction in All Diploid Organisms
2.7. Electron Microscopy Has Revealed the Physical Structure of Mitotic andMeiotic Chromosomes
Pubmed: Exploring and Retrieving Biomedical Literature
Case Study: Timing is Everything
Summary Points
Insights and Solutions
Problems and Discussion Questions
3. Mendelian Genetics3.1. Mendel Used a Model Experimental Approach to Study Patterns of Inheritance
3.2. The Monohybrid Cross Reveals How One Trait Is Transmitted from Generationto Generation
Mendel’s First Three Postulates
Modern Genetic Terminology
Mendel’s Analytical Approach
Table of Contents
Punnett Squares
The Testcross: One Character
3.3. Mendel’s Dihybrid Cross Generated a Unique F2 RatioMendel’s Fourth Postulate: Independent Assortment
The Testcross: Two Characters
Identifying Mendel’s Gene for Regulating White Flower Color in Peas
3.4. The Trihybrid Cross Demonstrates That Mendel’s Principles Apply toInheritance of Multiple Traits
The Forked-Line Method, or Branch Diagram
3.5. Mendel’s Work was Rediscovered in the Early Twentieth CenturyThe Chromosomal Theory of Inheritance
Unit Factors, Genes, and Homologous Chromosomes
3.6. Independent Assortment Leads to Extensive Genetic Variation
3.7. Laws of Probability Help to Explain Genetic EventsThe Binomial Theorem
3.8. Chi-Square Analysis Evaluates the Influence of Chance on Genetic DataChi-Square Calculations and the Null Hypothesis
Interpreting Probability Values
3.9. Pedigrees Reveal Patterns of Inheritance of Human TraitsPedigree Conventions
Pedigree Analysis
3.10. Mutant Phenotypes Have Been Examined at the Molecular LevelHow Mendel’s Peas Become Wrinkled: A Molecular Explanation
Tay—Sachs Disease: The Molecular Basis of a Recessive Disorder in Humans
Online Mendelian Inheritance in Man
Case Study: To Test or not to Test
Summary Points
Insights and Solutions
Problems and Discussion Questions
4. Extensions of Mendelian Genetics4.1. 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 ClearlyEvident
4.5. Multiple Alleles of a Gene May Exist in a PopulationThe ABO Blood Groups
The A and B Antigens
The Bombay Phenotype
Table of Contents
The White Locus in Drosophila
4.6. Lethal Alleles Represent Essential GenesThe Molecular Basis of Dominance, Recessiveness, and Lethality: The Agouti Gene
4.7. Combinations of Two Gene Pairs with Two Modes of Inheritance Modify the9:3:3:1 Ratio
4.8. Phenotypes are Often Affected by More Than One GeneEpistasis
Novel Phenotypes
Other Modified Dihybrid Ratios
4.9. Complementation Analysis Can Determine if Two Mutations Causing a SimilarPhenotype are Alleles of the Same Gene
4.10. Expression of a Single Gene May Have Multiple Effects
4.11. X-Linkage Describes Genes on the X ChromosomeX-Linkage in Drosophila
X-Linkage in Humans
4.12. In Sex-Limited and Sex-Influenced Inheritance, an Individual’s SexInfluences the Phenotype
4.13. Genetic Background and the Environment May Alter Phenotypic ExpressionPenetrance and Expressivity
Genetic Background: Position Effects
Temperature Effects—An Introduction to Conditional Mutations
Nutritional Effects
Onset of Genetic Expression
Genetic Anticipation
Genomic (Parental) Imprinting and Gene Silencing
Improving the Genetic Fate of Purebred Dogs
Case Study: But he isn’t Deaf
Summary Points
Insights and Solutions
Problems and Discussion Questions
5. Chromosome Mapping in Eukaryotes5.1. Genes Linked on the Same Chromosome Segregate Together
The Linkage Ratio
5.2. Crossing Over Serves as the Basis for Determining the Distance betweenGenes in Chromosome Mapping
Morgan and Crossing Over
Sturtevant and Mapping
Single Crossovers
5.3. Determining the Gene Sequence during Mapping Requires the Analysis ofMultiple Crossovers
Table of Contents
Multiple Exchanges
Three-Point Mapping in Drosophila
Determining the Gene Sequence
A Mapping Problem in Maize
5.4. As the Distance Between Two Genes Increases, Mapping Estimates Become MoreInaccurate
Interference and the Coefficient of Coincidence
5.5. Drosophila Genes Have Been Extensively Mapped
5.6. Lod Score Analysis and Somatic Cell Hybridization Were HistoricallyImportant in Creating Human Chromosome Maps
5.7. Chromosome Mapping is Now Possible Using DNA Markers and Annotated ComputerDatabases
5.8. Crossing Over Involves a Physical Exchange Between Chromatids
5.9. Exchanges Also Occur between Sister Chromatids during Mitosis
5.10. Did Mendel Encounter Linkage?
Human Chromosome Maps on the Internet
Case Study: Links to Autism
Summary Points
Insights and Solutions
Problems and Discussion Questions
6. Genetic Analysis and Mapping in Bacteria and Bacteriophages6.1. Bacteria Mutate Spontaneously and Grow at an Exponential Rate
6.2. Genetic Recombination Occurs in BacteriaConjugation in Bacteria: The Discovery of F+ and F- Strains
Hfr Bacteria and Chromosome Mapping
Recombination in F+ x F- Matings: A Reexamination
The F' State and Merozygotes
6.3. Rec Proteins are Essential to Bacterial Recombination
6.4. The F Factor Is an Example of a Plasmid
6.5. Transformation Is a Second Process Leading to Genetic Recombination inBacteria
The Transformation Process
Transformation and Linked Genes
6.6. Bacteriophages are Bacterial VirusesPhage T4: Structure and Life Cycle
The Plaque Assay
Lysogeny
6.7. Transduction Is Virus-Mediated Bacterial DNA TransferThe Lederberg–Zinder Experiment
Table of Contents
The Nature of Transduction
Transduction and Mapping
6.8. Bacteriophages Undergo Intergenic RecombinationBacteriophage Mutations
Mapping in Bacteriophages
6.9. Intragenic Recombination Occurs in Phage T4The rll Locus of Phage T4
Complementation by rll Mutations
Recombinational Analysis
Deletion Testing of the rll Locus
The rll Gene Map
From Cholera Genes to Edible Vaccines
Case Study: To Treat or not to Treat
Summary Points
Insights and Solutions
Problems and Discussion Questions
7. Sex Determination and Sex Chromosomes7.1. 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 theTwentieth Century
7.3. The Y Chromosome Determines Maleness in HumansKlinefelter 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 Excessive Expression of X-Linked Genes inMammals
Barr Bodies
The Lyon Hypothesis
The Mechanism of Inactivation
7.6. The Ratio of X Chromosomes to Sets of Autosomes Determines Sex inDrosophila
Dosage Compensation in Drosophila
Drosophila Mosaics
Drosophila Sxl Gene Induces Female Development
Table of Contents
7.7. Temperature Variation Controls Sex Determination in Reptiles
A Question of Gender: Sex Selection in Humans
Case Study: Doggone it!
Summary Points
Insights and Solutions
Problems and Discussion Questions
8. Chromosome Mutations: Variation in Number and Arrangement8.1. Variation in Chromosome Number: Terminology and Origin
8.2. Monosomy and Trisomy Result in a Variety of Phenotypic EffectsMonosomy
Trisomy
Down Syndrome: Trisomy 21
The Down Syndrome Critical Region (DSCR)
Mouse Models of Down SyndromeThe Origin of the Extra 21st Chromosome in Down Syndrome
Human Aneuploidy
8.3. Polyploidy, in Which More Than Two Haploid Sets of Chromosomes Are Present,Is Prevalent in Plants
Autopolyploidy
Allopolyploidy
Endopolyploidy
8.4. Variation Occurs in the Composition and Arrangement of Chromosomes
8.5. A Deletion is a Missing Region of a ChromosomeCri du Chat Syndrome in Humans
8.6. A Duplication Is a Repeated Segment of a ChromosomeGene Redundancy and Amplification—Ribosomal RNA Genes
The Bar Mutation in Drosophila
The Role of Gene Duplication in Evolution
Duplications at the Molecular Level: Copy Number Variants (CNVs)
8.7. Inversions Rearrange the Linear Gene SequenceConsequences of Inversions during Gamete Formation
Evolutionary Advantages of Inversions
8.8. Translocations Alter the Location of Chromosomal Segments in the GenomeTranslocations in Humans: Familial Down Syndrome
8.9. Fragile Sites in Human Chromosomes are Susceptible to BreakageFragile-X Syndrome
The Link Between Fragile Sites and Cancer
Down Syndrome and Prenatal Testing—The New Eugenics?
Case Study: Fish Tales
Table of Contents
Summary Points
Insights and Solutions
Problems and Discussion Questions
9. Extranuclear Inheritance9.1. Organelle Heredity Involves DNA in Chloroplasts and Mitochondria
Chloroplasts: Variegation in Four O’Clock Plants
Chloroplast Mutations in Chlamydomonas
Mitochondrial Mutations: Early Studies in Neurospora and Yeast
9.2. Knowledge of Mitochondrial and Chloroplast DNA Helps Explain OrganelleHeredity
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 DisordersMitochondria, Human Health, and Aging
Future Prevention of the Transmission of mtDNA-Based Disorders
9.4. In Maternal Effect, the Maternal Genotype Has a Strong Influence duringEarly Development
Lymnaea Coiling
Embryonic Development in Drosophila
Mitochondrial DNA and the Mystery of the Romanovs
Case Study: A Twin Difference
Summary Points
Insights and Solutions
Problems and Discussion Questions
10. DNA Structure and Analysis10.1. 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 duringthe 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 GeneticMaterial 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
Table of Contents
10.6. Knowledge of Nucleic Acid Chemistry Is Essential to the Understanding ofDNA Structure
Nucleotides: Building Blocks of Nucleic Acids
Nucleoside Diphosphates and Triphosphates
Polynucleotides
10.7. The Structure of DNA Holds the Key to Understanding Its FunctionBase-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 ofDNA and RNA
Absorption of Ultraviolet Light
Denaturation and Renaturation of Nucleic Acids
Molecular Hybridization
Fluorescent in situ Hybridization (FISH)
Reassociation Kinetics and Repetitive DNA
Electrophoresis of Nucleic Acids
Introduction to Bioinformatics: BLAST
Case Study: Zigs and Zags of the Smallpox Virus
Summary Points
Insights and Solutions
Problems and Discussion Questions
11. DNA Replication and Recombination11.1. 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 OtherEnzymes
DNA Polymerase I
DNA Polymerase II, III, IV, and V
The DNA Pol III Holoenzyme
11.3. Many Complex Issues Must Be Resolved During DNA ReplicationUnwinding the DNA Helix
Initiation of DNA Synthesis Using an RNA Primer
Continuous and Discontinuous DNA Synthesis
Concurrent Synthesis Occurs on the Leading and Lagging Strands
Proofreading and Error Correction Occurs During DNA Replication
Table of Contents
11.4. A Coherent Model Summarizes DNA Replication
11.5. Replication Is Controlled by a Variety of Genes
Lethal Knockouts of DNA Ligase Genes
11.6. Eukaryotic DNA Replication Is Similar to Replication in Prokaryotes, butIs More Complex
Initiation at Multiple Replication Origins
Multiple Eukaryotic DNA Polymerases
Replication through Chromatin
11.7. The Ends of Linear Chromosomes Are Problematic during ReplicationTelomere Structure
Replication at the Telomere
11.8. DNA Recombination, Like DNA Replication, Is Directed by Specific EnzymesModels of Homologous Recombination
Enzymes and Proteins Involved in Homologous Recombination
Gene Conversion, a Consequence of Homologous Recombination
Telomeres: The Key to Immortality?
Case Study: At Loose Ends
Summary Points
Insights and Solutions
Problems and Discussion Questions
12. DNA Organization in Chromosomes12.1. Viral and Bacterial Chromosomes Are Relatively Simple DNA Molecules
12.2. Supercoiling Facilitates Compaction of the DNA of Viral and BacterialChromosomes
12.3. Specialized Chromosomes Reveal Variations in the Organization of DNAPolytene Chromosomes
Lampbrush Chromosomes
12.4. DNA Is Organized into Chromatin in EukaryotesChromatin Structure and Nucleosomes
Chromatin Remodeling
Heterochromatin
12.5. Chromosome Banding Differentiates Regions along the Mitotic Chromosome
12.6. Eukaryotic Genomes Demonstrate Complex Sequence Organization Characterizedby Repetitive DNA
Satellite DNA
Centromeric 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
Table of Contents
Database of Genomic Variants: Structural Variations in the Human Genome
Case Study: Art Inspires Learning
Summary Points
Insights and Solutions
Problems and Discussion Questions
13. The Genetic Code and Transcription13.1. The Genetic Code Uses Ribonucleotide Bases as “Letters”
13.2. Early Studies Established the Basic Operational Patterns of the CodeThe Triplet Nature of the Code
The Nonoverlapping Nature of the Code
The Commaless and Degenerate Nature of the Code
13.3. Studies by Nirenberg, Matthaei, and Others Led to Deciphering of the CodeSynthesizing Polypeptides in a Cell-Free System
Homopolymer Codes
Mixed Copolymers
The Triplet-Binding Assay
Repeating Copolymers
13.4. The Coding Dictionary Reveals Several Interesting Patterns among the 64Codons
Degeneracy and the Wobble Hypothesis
The Ordered Nature of the Code
Initiation, Termination, and Suppression
13.5. The Genetic Code Has Been Confirmed in Studies of Phage MS2
13.6. The Genetic Code Is Nearly Universal
13.7. Different Initiation Points Create Overlapping Genes
13.8. Transcription Synthesizes RNA on a DNA Template
13.9. Studies with Bacteria and Phages Provided Evidence for the Existence ofmRNA
13.10. RNA Polymerase Directs RNA SynthesisPromoters, Template Binding, and the S Subunit
Initiation, Elongation, and Termination of RNA Synthesis
13.11. Transcription in Eukaryotes Differs from Prokaryotic Transcription inSeveral Ways
Initiation of Transcription in Eukaryotes
Recent Discoveries Concerning RNA Polymerase Function
Processing Eukaryotic RNA: Caps and Tails
13.12. The Coding Regions of Eukaryotic Genes Are Interrupted by InterveningSequences Called Introns
Splicing Mechanisms: Self-Splicing RNAs
Splicing Mechanisms: The Spliceosome
Table of Contents
13.13. RNA Editing May Modify the Final Transcript
13.14. Transcription Has Been Visualized by Electron Microscopy
Case Study: A Drug that Sometimes Works
Summary Points
Fighting Disease with Antisense Therapeutics
Insights and Solutions
Problems and Discussion Questions
14. Translation and Proteins14.1. Translation of mRNA Depends on Ribosomes and Transfer RNAs
Ribosomal Structure
tRNA Structure
Charging tRNA
14.2. Translation of mRNA Can Be Divided into Three StepsInitiation
Elongation
Termination
Polyribosomes
14.3. High-Resolution Studies Have Revealed Many Details about the FunctionalProkaryotic Ribosome
14.4. Translation Is More Complex in Eukaryotes
14.5. The Initial Insight That Proteins Are Important in Heredity Was Providedby the Study of Inborn Errors of Metabolism
Phenylketonuria
14.6. Studies of Neurospora Led to the One-Gene:One- Enzyme HypothesisAnalysis of Neurospora Mutants by Beadle and Tatum
Genes and Enzymes: Analysis of Biochemical Pathways
14.7. Studies of Human Hemoglobin Established That One Gene Encodes OnePolypeptide
Sickle-Cell Anemia
Human Hemoglobins
14.8. The Nucleotide Sequence of a Gene and the Amino Acid Sequence of theCorresponding Protein Exhibit Colinearity
14.9. Variation in Protein Structure Provides the Basis of Biological Diversity
14.10. Posttranslational Modification Alters the Final Protein ProductProtein Folding and Misfolding
14.11. Proteins Function in Many Diverse Roles
14.12. Proteins are Made Up of One or More Functional DomainsExon Shuffling
The Origin of Protein Domains
Table of Contents
Translation Tools and Swiss-Prot for Studying Protein Sequences
Case Study: Crippled Ribosomes
Summary Points
Insights and Solutions
Problems and Discussion Questions
15. Gene Mutation, DNA Repair, and Transposition15.1. Gene Mutations Are Classified in Various Ways
Classification Based on Type of Molecular Change
Classification Based on Phenotypic Effects
Classification Based on Location of Mutation
15.2. Mutations Occur Spontaneously and RandomlySpontaneous and Induced Mutations
Spontaneous Mutation Rates in Humans
The Fluctuation Test: Are Mutations Random or Adaptive?
15.3. Spontaneous Mutations Arise from Replication Errors and Base ModificationsDNA Replication Errors and Slippage
Tautomeric Shifts
Depurination and Deamination
Oxidative Damage
Transposable Elements
15.4. Induced Mutations Arise from DNA Damage Caused by Chemicals and RadiationBase Analogs
Alkylating, Intercalating, and Adduct-Forming Agents
Ultraviolet Light
Ionizing Radiation
15.5. Single-Gene Mutations Cause a Wide Range of Human DiseasesSingle Base-Pair Mutations and ?-Thalassemia
Mutations Caused by Expandable DNA Repeats
15.6. Organisms Use DNA Repair Systems to Counteract MutationsProofreading 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
15.7. The Ames Test Is Used to Assess the Mutagenicity of Compounds
15.8. Transposable Elements Move within the Genome and May Create MutationsInsertion Sequences and Bacterial Transposons
The Ac–Ds System in Maize
Copia and P Elements in Drosophila
Table of Contents
Transposable Elements in Humans
Transposon-Mediated Mutations Reveal Genes Involved in Colorectal Cancer
Transposons, Mutations, and Evolution
Sequence Alignment to Identify a Mutation
Case Study: Genetic Dwarfism
Summary Points
Insights and Solutions
Problems and Discussion Questions
16. Regulation of Gene Expression in Prokaryotes16.1. Prokaryotes Regulate Gene Expression in Response to EnvironmentalConditions
16.2. Lactose Metabolism in E. coli Is Regulated by an Inducible SystemStructural Genes
The Discovery of Regulatory Mutations
The Operon Model: Negative Control
Genetic Proof of the Operon Model
Isolation of the Repressor
16.3. The Catabolite-Activating Protein (CAP) Exerts Positive Control over thelac Operon
16.4. Crystal Structure Analysis of Repressor Complexes Has Confirmed the OperonModel
16.5. The Tryptophan (trp) Operon in E. coli Is a Repressible Gene SystemEvidence for the trp Operon
16.6. Alterations to RNA Secondary Structure Contribute to Prokaryotic GeneRegulation
Attenuation
Riboswitches
16.7. The ara Operon Is Controlled by a Regulator Protein That Exerts BothPositive and Negative Control
Case Study: Food Poisoning and Bacterial Gene Expression
Summary Points
Quorum Sensing: Social Networking in the Bacterial World
Insights and Solutions
Problems and Discussion Questions
17. Regulation of Gene Expression in Eukaryotes17.1. Eukaryotic Gene Regulation Can Occur at Any of the Steps Leading from DNAto Protein Product
17.2. Eukaryotic Gene Expression Is Influenced by Chromatin ModificationsChromosome Territories and Transcription Factories
Table of Contents
Open and Closed Chromatin
Histone Modifications and Nucleosomal Chromatin Remodeling
DNA Methylation
17.3 Eukaryotic Transcription Initiation Requires Specific Cis-Acting SitesPromoter Elements
Enhancers and Silencers
17.4. Eukaryotic Transcription Initiation Is Regulated by Transcription FactorsThat Bind to Cis-Acting Sites
The Human Metallothionein IIA Gene: Multiple Cis-Acting Elements and
Transcription Factors
Functional Domains of Eukaryotic Transcription Factors
17.5. Activators and Repressors Interact with General Transcription Factors andAffect Chromatin Structure
Formation of the RNA Polymerase II Transcription Initiation Complex
Mechanisms of Transcription Activation and Repression
17.6. Gene Regulation in a Model Organism: Transcription of the GAL Genes ofYeast
17.7. Posttranscriptional Gene Regulation Occurs at Many Steps from RNAProcessing to Protein Modification
Alternative Splicing of mRNA
Alternative Splicing and Human Diseases
Sex Determination in Drosophila: A Model for Regulation of Alternative Splicing
Control of mRNA Stability
Translational and Posttranslational Regulation
17.8. RNA Silencing Controls Gene Expression in Several WaysThe Molecular Mechanisms of RNA-Induced Gene Silencing
RNA-Induced Gene Silencing in Biotechnology and Medicine
MicrorRNAs Regulate Ovulation in Female Mice
17.9. Programmed DNA Rearrangements Regulate Expression of a Small Number ofGenes
The Immune System and Antibody Diversity
Gene Rearrangements in the K Light-Chain Gene
17.10. ENCODE Data are Transforming Our Concepts of Eukaryotic Gene RegulationEnhancer and Promoter Elements
Transcripts and RNA Processing
Tissue-Specific Gene Expression
Case Study: A Mysterious Muscular Dystrophy
Summary Points
Insights and Solutions
Problems and Discussion Questions
Table of Contents
18. Developmental Genetics18.1. Differentiated States Develop from Coordinated Programs of Gene Expression
18.2. Evolutionary Conservation of Developmental Mechanisms Can Be Studied UsingModel Organisms
Analysis of Developmental Mechanisms
18.3. Genetic Analysis of Embryonic Development in Drosophila Reveals How theBody Axis of Animals Is Specified
Overview of Drosophila Development
Genetic Analysis of Embryogenesis
18.4. Zygotic Genes Program Segment Formation in DrosophilaGap Genes
Pair-Rule Genes
Segment Polarity Genes
Segmentation Genes in Mice and Humans
18.5. Homeotic Selector Genes Specify Body Parts of the AdultHox Genes in Drosophila
Hox Genes and Human Genetic Disorders
18.6. Plants Have Evolved Developmental Regulatory Systems That Parallel Thoseof Animals
Homeotic Genes in Arabidopsis
Evolutionary Divergence in Homeotic Genes
18.7. C. elegans Serves as a Model for Cell–Cell Interactions in DevelopmentSignaling Pathways in Development
Single-Gene Signaling Mechanism Reveals Secrets to Head Regeneration in PlanariaThe Notch Signaling Pathway
Overview of C. elegans Development
Genetic Analysis of Vulva Formation
18.8. Binary Switch Genes and Signaling Pathways Program Genomic ExpressionThe Control of Eye Formation
Stem Cell Wars
Case Study: One Foot or Another
Summary Points
Insights and Solutions
Problems and Discussion Questions
19. Cancer and Regulation of the Cell Cycle19.1. Cancer Is a Genetic Disease at the Level of Somatic Cells
What Is Cancer?
The Clonal Origin of Cancer Cells
The Cancer Stem Cell Hypothesis
Cancer as a Multistep Process, Requiring Multiple Mutations
Table of Contents
Driver Mutations and Passenger Mutations
19.2. Cancer Cells Contain Genetic Defects Affecting Genomic Stability, DNARepair, and Chromatin Modifications
Genomic Instability and Defective DNA Repair
Chromatin Modifications and Cancer Epigenetics
19.3. Cancer Cells Contain Genetic Defects Affecting Cell-Cycle RegulationThe Cell Cycle and Signal Transduction
Cell-Cycle Control and Checkpoints
Control of Apoptosis
19.4. Proto-Oncogenes and Tumor-Suppressor Genes are Altered in Cancer CellsThe ras Proto-Oncogenes
The p53 Tumor-Suppressor Gene
The RB1 Tumor-Suppressor Gene
19.5. Cancer Cells Metastasize and Invade Other Tissues
19.6. Predisposition to Some Cancers Can Be Inherited
19.7. Viruses Contribute to Cancer in Both Humans and Animals
19.8. Environmental Agents Contribute to Human Cancers
The Cancer Genome Anatomy Project (CGAP)
Case Study: I Thought it was Safe
Summary Points
Insights and Solutions
Problems and Discussion Questions
20. Recombinant DNA Technology20.1. Recombinant DNA Technology Began with Two Key Tools: Restriction Enzymesand DNA Cloning Vectors
Restriction Enzymes Cut DNA at Specific Recognition Sequences
DNA Vectors Accept and Replicate DNA Molecules to Be Cloned
Bacterial Plasmid Vectors
Other Types of Cloning Vectors
Ti Vectors for Plant Cells
Host Cells for Cloning Vectors
20.2. DNA Libraries are Collections of Cloned SequencesGenomic Libraries
Complementary DNA (cDNA) Libraries
Specific Genes Can Be Recovered from a Library by Screening
20.3. The Polymerase Chain Reaction Is a Powerful Technique for Copying DNALimitations of PCR
Applications of PCR
20.4. Molecular Techniques for Analyzing DNARestriction Mapping
Table of Contents
Nucleic Acid Blotting
20.5. DNA Sequencing Is the Ultimate Way to Characterize DNA Structure at theMolecular Level
Sequencing Technologies Have Progressed Rapidly
Next-Generation and Third-Generation Sequencing Technologies
DNA Sequencing and Genomics
20.6. Creating Knockout and Transgenic Organisms for Studying Gene FunctionGene Targeting and Knockout Animal Models
Making a Transgenic Animal: The Basics
Manipulating Recombinant DNA : Restriction Mapping and Designing PCR Primers
Case Study: Should we worry about Recombinant DNA Technology?
Summary Points
Insights and Solutions
Problems and Discussion Questions
21. Genomics, Bioinformatics, and Proteomics21.1. Whole-Genome Sequencing Is a Widely Used Method for Sequencing andAssembling Entire Genomes
High-Throughput Sequencing and Its Impact on Genomics
The Clone-By-Clone Approach
Draft Sequences and Checking for Errors
21.2. DNA Sequence Analysis Relies on Bioinformatics Applications and GenomeDatabases
Annotation to Identify Gene Sequences
Hallmark Characteristics of a Gene Sequence Can Be Recognized During Annotation
21.3. Genomics Attempts to Identify Potential Functions of Genes and OtherElements in a Genome
Predicting Gene and Protein Functions by Sequence Analysis
Predicting Function from Structural Analysis of Protein Domains and Motifs
Investigators Are Using Genomics Techniques Such as Chromatin
Immunoprecipitation to Investigate Aspects of Genome Function and Regulation
21.4. The Human Genome Project Revealed Many Important Aspects of GenomeOrganization in Humans
Origins of the Project
Major Features of the Human Genome
Individual Variations in the Human Genome
Accessing the Human Genome Project on the Internet
21.5. The Omics Revolution Has Created a New Era of Biological ResearchStone-Age Genomics
After the HGP: What Is Next?
Personal Genome Projects and Personal Genomics
Table of Contents
Exome Sequencing
Encyclopedia of DNA Elements (ENCODE) Project
The Human Microbiome Project
No Genome Left Behind and the Genome 10K Plan
21.6. Comparative Genomics Analyzes and Compares Genomes from DifferentOrganisms
Prokaryotic and Eukaryotic Genomes Display Common Structural and Functional
Features and Important Differences
Comparative Genomics Provides Novel Information about the Genomes of Model
Organisms and the Human Genome
The Sea Urchin Genome
The Dog Genome
The Chimpanzee Genome
The Rhesus Monkey Genome
The Neanderthal Genome and Modern Humans
21.7. Comparative Genomics Is Useful for Studying the Evolution and Function ofMultigene Families
21.8. Metagenomics Applies Genomics Techniques to Environmental Samples
21.9. Transcriptome Analysis Reveals Profiles of Expressed Genes in Cells andTissues
Microarray Analysis
21.10. Proteomics Identifies and Analyzes the Protein Composition of CellsReconciling 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 Fossils
21.11. Systems Biology Is an Integrated Approach to Studying Interactions of AllComponents of an Organisms Cells
Contigs, Shotgun Sequencing, and Comparative Genomics
Case Study: Your Microbiome may be a Risk Factor for Disease
Summary Points
Insights and Solutions
Problems and Discussion Questions
22. Applications and Ethics of Genetic Engineering and Biotechnology22.1. Genetically Engineered Organisms Synthesize a Wide Range of Biological andPharmaceutical Products
Insulin Production in Bacteria
Transgenic Animal Hosts and Pharmaceutical Products
Recombinant DNA Approaches for Vaccine Production
Table of Contents
Vaccine Proteins Can Be Produced by Plants
DNA-Based Vaccines
22.2. Genetic Engineering of Plants Has Revolutionized Agriculture
22.3. Transgenic Animals Serve Important Roles in BiotechnologyExamples of Transgenic Animals
22.4. Synthetic Genomes and the Emergence of Synthetic BiologyHow Simple Can a Genome Be?
Transplantation of a Synthetic Genome
Synthetic Biology for Bioengineering Applications
22.5. Genetic Engineering and Genomics Are Transforming Medical DiagnosisPrenatal Genetic Testing
Genetic Tests Based on Restriction Enzyme Analysis
Genetic Testing 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
22.6. Genetic Analysis by Individual Genome Sequencing
22.7. Genome-Wide Association Studies Identify Genome Variations That Contributeto Disease
22.8. Genomics Leads to New, More Targeted Medical Treatment IncludingPersonalized Medicine
Pharmacogenomics and Rational Drug Design
Gene Therapy
22.9. Genetic Engineering, Genomics, and Biotechnology Create Ethical, Social,and Legal Questions
Genetic Testing and Ethical Dilemmas
Direct-To-Consumer Genetic Testing and Regulating the Genetic Test Providers
DNA and Gene Patents
Whole Genome Sequence Analysis Presents Many Questions of Ethics
Preconception Testing, Destiny Predictions, and Baby- Predicting Patents
Patents and Synthetic Biology
Privacy and Anonymity in the Era of Genomic Big Data
Case Study: Cancer-Killing Bacteria
Summary Points
Insights and Solutions
Problems and Discussion Questions
23. Quantitative Genetics and Multifactorial Traits23.1. Not All Polygenic Traits Show Continuous Variation
23.2. Quantitative Traits Can Be Explained in Mendelian Terms
Table of Contents
The Multiple-Gene Hypothesis for Quantitative Inheritance
Additive Alleles: The Basis of Continuous Variation
Calculating the Number of Polygenes
23.3. The Study of Polygenic Traits Relies on Statistical AnalysisThe Mean
Variance
Standard Deviation
Standard Error of the Mean
Covariance and Correlation Coefficient
Analysis of a Quantitative Character
23.4. Heritability Values Estimate the Genetic Contribution to PhenotypicVariability
Broad-Sense Heritability
Narrow-Sense Heritability
Artificial Selection
23.5. Twin Studies Allow an Estimation of Heritability in HumansTwin Studies Have Several Limitations
23.6. Quantitative Trait Loci are Useful in Studying Multifactorial PhenotypesExpression QTLs (eQTLs) and Genetic Disorders
The Green Revolution Revisited: Genetic Research with Rice
Case Study: A Genetic Flip of the Coin
Summary Points
Insights and Solutions
Problems and Discussion Questions
24. Neurogenetics24.1 The Central Nervous System Receives Sensory Input and Generates BehavioralResponses
Organization of Cells in the Central Nervous System
Synapses Transfer Information Between Neurons
24.2. Identification of Genes Involved in Transmission of Nerve Impulses
24.3. Synapses Are Involved in Many Human Behavioral DisordersA Defect in Neurotransmitter Breakdown
Fragile-X Syndrome and Synapses
24.4. Animal Models Play an Important Role in the Study of Huntington Diseaseand Learning Behavior
Huntington Disease is a Neurodegenerative Behavioral Disorder
A Transgenic Mouse Model of Huntington Disease
Mechanism of Huntington Disease
Treatment Strategies for Huntington Disease
Drosophila as an Animal Model for Learning and Memory
Table of Contents
Dissecting the Mechanisms and Neural Pathways in Learning
Drosophila is an Effective Model for Learning and Memory in Humans
24.5. Behavioral Disorders Have Environmental ComponentsRbAp48 and a Potential Molecular Mechanism for Age-Related Memory Loss
Schizophrenia Is a Complex Behavioral Disorder
Several Behavioral Disorders Share a Genetic Relationship
Epigenetics and Mental Illness
Addiction and Alcoholism Are Behaviors with Genetic and Environmental Causes
Case Study: Primate Models for Human Disorders
Homologene: Searching for Behavioral Genes
Summary Points
Insights and Solutions
Problems and Discussion Questions
25. Population and Evolutionary Genetics25.1. Genetic Variation Is Present in Most Populations and Species
Detecting Genetic Variation by Artificial Selection
Variations in Nucleotide Sequence
Explaining the High Level of Genetic Variation in Populations
25.2. The Hardy–Weinberg Law Describes Allele Frequencies and GenotypeFrequencies in Populations
25.3. The Hardy–Weinberg Law Can Be Applied to Human PopulationsTesting for Hardy–Weinberg Equilibrium in a Population
Calculating Frequencies for Multiple Alleles in Populations
Calculating Allele Frequencies for X-Linked Traits
Calculating Heterozygote Frequency
25.4. Natural Selection Is a Major Force Driving Allele Frequency ChangeDetecting Natural Selection in Populations
Fitness and Selection
There are Several Types of Selection
25.5. Mutation Creates New Alleles in a Gene Pool
25.6. Migration and Gene Flow Can Alter Allele Frequencies
25.7. Genetic Drift Causes Random Changes in Allele Frequency in SmallPopulations
Founder Effects in Human Populations
25.8. Nonrandom Mating Changes Genotype Frequency but Not Allele FrequencyInbreeding
25.9. Reduced Gene Flow, Selection, and Genetic Drift Can Lead to SpeciationChanges Leading to Speciation
The Rate of Macroevolution and Speciation
25.10. Phylogeny Can Be Used to Analyze Evolutionary History
Table of Contents
Constructing Phylogenetic Trees from Amino Acid Sequences
Molecular Clocks Measure the Rate of Evolutionary Change
Genomics and Molecular Evolution
The Complex Origins of Our Genome
Our Genome Is a Mosaic
Tracking Our Genetic Footprints out of Africa
Case Study: An Unexpected Outcome
Summary Points
Insights and Solutions
Problems and Discussion Questions
EpigeneticsEpigenetic Alterations to the Genome
DNA Methylation
Histone Modification and Chromatin Remodeling
MicroRNAs and Long Noncoding RNAs
Epigenetics and ImprintingAssisted Reproductive Technologies (ART) and Imprinting Defects
Epigenetics and Cancer
Epigenetics and the Environment
Epigenome Projects
Emerging Roles of RNACatalytic Activity of RNAs: Ribozymes and the Origin of Life
Genetic Engineering of Ribozymes
Small Noncoding RNAs Play Regulatory Roles in Prokaryotes
Prokaryotes Have an RNA-Guided Viral Defense Mechanism
Small Noncoding RNAs Mediate the Regulation of Eukaryotic Gene ExpressionsiRNAs and RNA Interference
miRNAs Regulate Posttranscriptional Gene Expression
piRNAs Protect the Genome for Future Generations
RNA-Induced Transcriptional Silencing
Long Noncoding RNAs Are Abundant and Have Diverse FunctionslncRNAs Mediate Transcriptional Repression by Interacting with
Chromatin-Regulating Complexes
lncRNAs Regulate Transcription Factor Activity
Circular RNAs Act as Sponges to Soak Up MicroRNAs
mRNA Localization and Translational Regulation in Eukaryotes
DNA ForensicsDNA Profiling Methods
VNTR-Based DNA Fingerprinting
Table of Contents
Autosomal STR DNA Profiling
Y-Chromosome STR Profiling
Mitochondrial DNA Profiling
Single-Nucleotide Polymorphism Profiling
Interpreting DNA ProfilesThe Uniqueness of DNA Profiles
The Prosecutor’s Fallacy
DNA Profile Databases
Technical and Ethical Issues Surrounding DNA Profiling
Genomics and Personalized MedicinePersonalized Medicine and Pharmacogenomics
Optimizing Drug Therapies
Reducing Adverse Drug Reactions
Personalized Medicine and Disease DiagnosticsPersonal Genomics and Cancer
Personal Genomics and Disease Diagnosis: Analyzing One Genome
Technical, Social, and Ethical Challenges
Genetically Modified FoodsWhat are GM Foods?
Herbicide-Resistant GM Crops
Insect-Resistant GM Crops
GM Crops for Direct Consumption
Methods Used to Create GM PlantsSelectable Markers
Roundup-Ready® Soybeans
Golden Rice 2
GM Foods ControversiesHealth and Safety
Environmental Effects
The Future of GM Foods
Gene TherapyWhat Genetic Conditions Are Candidates for Treatment by Gene Therapy?
How Are Therapeutic Genes Delivered?Viral Vectors for Gene Therapy
Nonviral Delivery Methods
The First Successful Gene Therapy Trial
Gene Therapy SetbacksProblems with Gene Therapy Vectors
Recent Successful Trials
Table of Contents
Treating Retinal Blindness
HIV as a Vector Shows Promise in Recent Trials
Targeted Approaches to Gene TherapyDNA-Editing Nucleases for Gene Targeting
RNA Silencing for Gene Inhibition
Future Challenges and Ethical IssuesEthical Concerns Surrounding Gene Therapy
Appendix A: Selected Readings
Appendix B: Answers to Selected Problems
Glossary
Credits
Index
EndPapersNobel Laureates
Back Cover