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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


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



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



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



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



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



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



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



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



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



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



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



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



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



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



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



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



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



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



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



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



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



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



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



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

edglob iti onl concepts of genetics

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