C O N C E P T S O F

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WILLIAM S. KLUGThe College of New Jersey

MICHAEL R. CUMMINGSUniversity of Illinois, Chicago

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Spencer University of Alberta, Edmonton

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B R I N T N T

An Introduction to Genetics, 1

PART ONE23

45

678

9

PART TWO10

n1213

141516

17

PART THREE18

19202122

2324

25

APPENDIX A:APPENDIX B:APPENDIX C:CREDITSINDEX

HEREDITY AND THE PHENOTYPE, 17Cell Division and Chromosomes, 18Mendelian Genetics, 50Modification of Mendelian Ratios, 79Linkage, Crossing Over, and Chromosome Mapping, 115Recombination and Mapping in Bacteria and Bacteriophages, 149Extensions of Genetic Analysis, 180Extranuclear Inheritance, 208Chromosome Variation and Sex Determination, 221

MOLECULAR BASIS OF HEREDITY, 261Structure and Analysis of DNA and RNA, 262DNA Replication and Recombination, 298Storage and Expression of Genetic Information, 324Proteins: The End Product of Genetic Expression, 364Gene Mutation, DNA Repair, and Transposable Elements, 389Recombinant DNA Technology, 428Applications of Recombinant DNA Technology, 461Genomic Organization of DNA, 490

ADVANCED TOPICS IN GENETIC ANALYSIS, 521Regulation of Gene Expression in Bacteria and Phages, 522Regulation of Gene Expression in Eukaryotes, 544Developmental Genetics, 567Genetics and Cancer, 591Genetic Basis of the Immune Response, 614The Genetics of Behavior, 637Population Genetics, 659Genetics and Evolution, 681

Experimental Methods A-1Glossary B-lSolutions to Selected Even-Numbered Problems and Discussion Questions C-lCR-11-1

N N

1 An Introduction to Genetics, 1The Historical Context of Genetics 2

Prehistoric Domestication of Animals and Cultivationof Plants 2The Greek Influence: Hippocrates and Aristotle 2The Dawn of Modern Biology: 1600-1850 3Darwin: The Gap in His Theory of Evolution 4Mendel: An Experimental Biologist 5

Basic Concepts of Genetics 6Investigative Approaches in Genetics 9Genetics and Society 10 y

Eugenics: The Misguided Application of Science 10

Soviet Science: The Lysenko Affair 11

GENETICS, TECHNOLOGY, AND SOCIETYA New Era in Plant Genetics: The Flavr SawTomato and Edible Vaccines 12

Genetic Advances in Agriculture and Medicine 12

PART ONEHEREDITY AND THE PHENOTYPE 17

2 Cell Division and Chromosomes 18Cell Structure 19

Cell Boundaries 19The Nucleus 20The Cytoplasm and Organelles 21

Homologous Chromosomes, Haploidy, andDiploidy 22Mitosis and Cell Division 2 5

Interphase and the Cell Cycle 25Prophase 26

Prometaphase and Metaphase 27Anaphase 27Telophase 29

Genetic Regulation of the Cell Cycle 30Meiosis and Sexual Reproduction 31

An Overview of Meiosis 32The First Meiotic Division: Prophase 132Metaphase, Anaphase, and Telophase 133

Spermatogenesis and Oogenesis 36The Significance of Meiosis 36The Cytological Origin of the Mitotic and MeioticChromosome 39The Synaptonemal Complex 40Specialized Chromosomes 42

Polytene Chromosomes 42Lampbrush Chromosomes 43

Mendelian Genetics 50Gregorjohann Mendel 51

Mendel's Experimental Approach 51

The Monohybrid Cross 51Mendel's First Three Postulates 53Modern Genetic Terminology 54Mendel's Analytical Approach 55Punnett Squares 55The Test Cross: One Character 55

The Dihybrid Cross 56Mendel's Fourth Postulate: IndependentAssortment 56The Test Cross: Two Characters 57

The Trihybrid Cross 59The Forked-Line Method, or Branch Diagram 59

The Rediscovery of Mendel's Work 61The Rebirth of Mendelian Genetics 61Unit Factors, Genes, and HomologousChromosomes 62

Independent Assortment and Genetic Variation 63Probability and Genetic Events 63

The Product Law and Sum Law 63Conditional Probability 64The Binomial Theorem 65

Evaluating Genetic Data: Chi-Square Analysis 66Human Pedigrees 69

Xlll

XIV CONTENTS

4 Modification of Mendelian Ratios 79Potential Function of an Allele 80Symbols for Alleles 80Incomplete, or Partial, Dominance 81Codominance 82Multiple Alleles 83

The ABO Blood Groups 83The A and B Antigens 83The Bombay Phenotype 85The Secretor Locus 85The Rh Antigens 85The white Locus in Drosophila 86

Lethal Alleles 86Combinations of Two Gene Pairs 88Gene Interaction: Discontinuous Variation 89

Epistasis 89Novel Phenotypes 93Other Modified Dihybrid Ratios 95

Gene Interaction: Continuous Variation 95Quantitative Inheritance: Polygenes 95Calculating the Number of Polygenes 99The Significance of Polygenic Control 100

Genes on the X Chromosome: X-Linkage 100X-Linkage in Drosophila 100X-Linkage in Humans 102Sex-Limited and Sex-Influenced Inheritance 103

GENETICS, TECHNOLOGY, AND SOCIETYThe Uncertain Genetic Fate of Purebred Dogs 104

5 Linkage, Crossing Over, andChromosome Mapping 115Linkage versus Independent Assortment 116

The Linkage Ratio 116Incomplete Linkage, Crossing Over, andChromosome Mapping 118

Morgan and Crossing Over 119Sturtevant and Mapping 119Single Crossovers 121Multiple Crossovers 121Three-Point Mapping in Drosophila 122Determining the Gene Sequence 124A Mapping Problem in Maize 126Interference and the Coefficient of Coincidence 129

The Inaccuracy of Mapping Experiments 130The Genetic Map of Drosophila 131

Other Aspects of Genetic Exchange 131Crossing Over in the Four-Strand Stage 132Cytological Evidence for Crossing Over 134The Mechanism of Crossing Over 135Mitotic Recombination 136Sister Chromatid Exchanges 137

Somatic Cell Hybridization and HumanChromosome Maps 138Did Mendel Encounter Linkage? 140

Why Didn 't Gregor Mendel Find Linkage? 141

6 Recombination and Mapping inBacteria and Bacteriophages 149Bacterial Mutation and Growth 150Genetic Recombination in Bacteria:Conjugation 151

F+ and F~ Bacteria 152Hfr Bacteria and Chromosome Mapping 154Recombination in F+ X F~ Matings:A Reexamination 156The F' State and Merozygotes 157

The Rec Proteins and BacterialRecombination 158Plasmids 158Bacterial Transformation 160

Transformation and Mapping 161The Genetic Study of Bacteriophages 162

Phage T4 Infection and Reproduction 162The Plaque Assay 164Lysis and Lysogeny 165

Transduction: Virus-Mediated Bacterial DNATransfer 165

The Lederberg-Zinder Experiment 165The Nature of Transduction 166 y

Mapping and Specialized Transduction 167Mutation and Recombination in Viruses 168

Genetic Exchange between Bacterial Viruses 168Intragenic Recombination in Phage T4 169

The rll Locus of Phage T4 170Complementation by rll Mutations 170Recombinational Analysis 172Deletion Testing of the rll Locus 172The rll Gene Map 174

7 Extensions of Genetic Analysis 180Phenotypic Expression 181

Penetrance and Expressivity 181

CONTENTS XV

Genetic Background: Suppression and PositionEffects 182Temperature Effects 182Nutritional Effects 183Onset of Genetic Expression 184Genetic Anticipation 184Genomic (Parental) Imprinting 185

Continuous Variation and Polygenes 186Continuous versus Discontinuous Variation 186Mapping Quantitative Trait Loci 187

Analysis of Polygenic Traits 188The Mean 189Variance 189Standard Deviation 190Standard Error of the Mean 190Analysis of a Quantitative Character 190

Heritability 192Broad-Sense Heritability 192Narrow-Sense Heritability 192Artificial Selection 193Twin Studies in Humans 193

The Use of Haploid Organisms in Linkage andMapping Studies 194

Gene-to-Centromere Mapping 195Ordered versus Unordered Tetrad Analysis 196Linkage and Gene Mapping in HaploidOrganisms 197

GENETICS, TECHNOLOGY, AND SOCIETYPreserving Plant Germplasm: The Key to theFuture of Agriculture 200

8 Extranuclear Inheritance 208Maternal Effect 209

Ephestia Pigmentation 209Limnaea Coiling 209Embryonic Development in Drosophila 210

Organelle Heredity 211Chloroplasts: Variegation in Four O'Clock Plants 211Iojap in Maize 211Chlamydomonas Mutations 212

Mitochondria: poky in Neurospora 213

Petite in Saccharomyces 213

Mitochondrial DNA and Human Diseases 214Infectious Heredity 216

Kappa in Paramecium 216Infective Particles in Drosophila 217

9 Chromosome Variation and SexDetermination 221Variation in Chromosome Number:An Overview 222

The Diploid Chromosome Number inHumans 222

Chromosomes, Sex Differentiation, and SexDetermination in Humans, 222

Klinefelter and Turner Syndromes 22347,XXX Syndrome 22347,XYY Condition 223Sexual Differentiation in Humans 225The Y Chromosome and Male Development 226Sex Ratio in Humans 226

Dosage Compensation in Humans 227Barr Bodies 227The Lyon Hypothesis 228The Mechanism of Inactivation 229

Chromosome Composition and Sex Determinationin Drosophila 230

Dosage Compensation in Drosophila 232Drosophila Mosaics 233

Aneuploidy 234Monosomy 234Partial Monosomy: Cri-du-Chat Syndrome 234Trisomy 235Down Syndrome 236Patau Syndrome 237Edwards Syndrome 237

Viability in Human Aneuploidy 238

Polyploidy and Its Origins 238Autopolyploidy 239Allopolyploidy 240Endopolyploidy 242 y~

Variation in Chromosome Structure andArrangement: An Overview 243Deletions 243Duplications 244

Gene Redundancy and Amplification: Ribosomal RNAGenes 244The Bar Eye Mutation in Drosophila 245The Role of Gene Duplication in Evolution 246

Inversions 247Consequences of Inversions during GameteFormation 248Position Effects of Inversions 248Evolutionary Consequences of Inversions 250

XVI CONTENTS

Translocations 250Translocations in Humans: Familial DownSyndrome 251

Fragile Sites in Humans 252Fragile X Syndrome (Martin-Bell Syndrome) 253FH1TGene and Human Lung Cancer 253

PART TWOMOLECULAR BASIS OF HEREDITY 261

10 Structure and Analysis of DNAand RNA 262Characteristics of the Genetic Material 263The Genetic Material: 1900-1944 264Evidence Favoring DNA as the Genetic Material inBacteria and Bacteriophages 264

Transformation Studies 265The Hershey-Chase Experiment 268Transfection Experiments 269

Indirect Evidence Favoring DNA inEukaryotes 271

Distribution of DNA 271Mutagenesis 271

Direct Evidence for DNA: Eukaryotic Data 271RNA as the Genetic Material 272Nucleic Acid Chemistry 273

Nucleotides: Building Blocks of Nucleic Acids 274Nucleoside Diphosphates and Triphosphates 275Polynucleotides 275

The Structure of DNA 277Base Composition Studies 277X-Ray Diffraction Analysis 277The Watson-Crick Model 278

Molecular Structure of Nucleic Acids: A Structure forDeoxyribose Nucleic Acid 280

Other Forms of DNA 283The Structure of RNA 283Analysis of Nucleic Acids 285

Absorption of Ultraviolet Light (UV) 285Sedimentation Behavior 285Denaturation and Renaturation of Nucleic Acids 287Molecular Hybridization 288Reassociation Kinetics and Repetitive DNA 288Electrophoresis of Nucleic Acids 291

11 DNA Replication andRecombination 298The Mode of DNA Replication 299

The Meselson-Stahl Experiment 300Semiconservative Replication in Eukaryotes 300Origins, Forks, and Units of Replication 303

Synthesis of DNA in Microorganisms 303DNA Polymerase I 304Fidelity of Synthesis 305Synthesis of Biologically Active DNA 306DNA Polymerase II and III 308

DNA Synthesis: A Model 309Unwinding the DNA Helix 309Initiation of Synthesis 310Continuous and Discontinuous DNA Synthesis 311Concurrent Synthesis on the Leading and LaggingStrands 311Proofreading 312 /

Summary of DNA Synthesis 313Genetic Control of Replication 313Eukaryotic DNA Synthesis 315

DNA Synthesis at the Ends of LinearChromosomes 315

DNA Recombination 317Gene Conversion 317

12 Storage and Expression of GeneticInformation 324An Overview of the Genetic Code 325Early Thinking about the Code 325The Code: Further Developments 326

The Study of Frameshift Mutations 326Deciphering the Code: Initial Studies 327

Nirenberg and Matthaei's Homopolymer Codes 328The Use of Mixed Copolymers 328The Triplet Binding Technique 330The Use of Repeating Copolymers 331

CONTENTS XVII

The Coding Dictionary 332Degeneracy and Wobble, and Order in the Code 332Initiation, Termination, and Suppression 333

Confirmation of Code Studies: Phage MS2 334Universality of the Code 334Reading the Code: The Case of OverlappingGenes 335

Expression of Genetic Information:An Overview 336Transcription: RNA Synthesis 336

Experimental Evidence for the Existence ofmRNA 337RNA Polymerase 337Promoters, Template Binding, and the SigmaSubunit 338The Synthesis of RNA 338Visualization of Transcription 341

Transcription in Eukaryotes 341Eukaryotic Promoters, Enhancers, and TranscriptionFactors 341Heterogeneous Nuclear RNA and Its Processing:Caps and Tails 342Intervening Sequences and Split Genes 343Splicing Mechanisms: Autocatalytic RNAs 345Splicing Mechanisms: The Spliceosome 346RNA Editing 346

Translation: Components Necessary for ProteinSynthesis 347

Ribosomal Structure 347tRNA Structure 349Charging tRNA 350

Translation: The General Process 351Initiation (Steps 1-3) 351Elongation (Steps 4-9) 354Termination (Steps 10-11) 354Polyribosomes 355

Translation in Eukaryotes 355

GENETICS, TECHNOLOGY, AND SOCIETYGenetic Testing Dilemmas: Sickle-Cell Anemiaand Breast Cancer 356

13 Proteins: The End Product of GeneExpression 364Garrod and Bateson: Inborn Errors ofMetabolism 365

Phenylketonuria 366

The One-Gene: One-Enzyme Hypothesis 366Beadle and Ephrussi: Drosophila Eye Pigments 366

Beadle and Tatum: Neurospora Mutants 368Genes and Enzymes: Analysis of BiochemicalPathways 370

One-Gene: One-Protein/One-Gene: One-Polypeptide 370

Sickle-Cell Anemia 371Human Hemoglobins 373

Colinearity 373Protein Structure and Function 374

Protein Structure 374Chaperones and Protein Folding 377Posttranslational Modification and ProteinTargeting 378 ' .Protein Function 379Protein Structure and Function: The CollagenFiber 380The Genetics of Collagen 380

GENETICS, TECHNOLOGY, AND SOCIETYPrions, Mad Cows, and Heresies 3 82

14 Gene Mutation, DNA Repair, andTransposable Elements 389Random versus Adaptive Mutations 390

The Luria-Delbruck Fluctuation Test 390Adaptive Mutation in Bacteria 391

Classification of Mutations 392Spontaneous versus Induced Mutations 392Gametic versus Somatic Mutations 393Other Categories of Mutation 393

Detection of Mutations 394Detection in Bacteria and Fungi 394Detection in Drosophila 394Detection in Plants 396Detection in Humans 397

^~">ntaneous Mutation Rate 397Moit^clar Basis of Mutation 400

Tautomeric Shifts 400Base Analogues 402Alkylating Agents 402Acridine Dyes and Frameshift Mutations 403Apurinic Sites and Other Lesions 405Ultraviolet Radiation, Thymine Dimers, and the SOSResponse 406

Case Studies of Mutations in Humans 407ABO Blood Types versus Muscular Dystrophy 407Trinucleotide Repeats in Fragile-X Syndrome,Myotonic Dystrophy, and Huntington Disease 408

Detection of Mutagenicity: The Ames Test 409

XVlll CONTENTS

Repair of DNA 409UV Radiation, Thymine Dimers, andPhotoreactivation Repair 409Excision Repair 410Proofreading and Mismatch Repair 411The SOS Response: Recombinational Repair 411

UV Radiation and Human Skin Cancer:Xeroderma Pigmentosum 412

Somatic Cell Hybridization, XP, and ExcisionRepair 413

High-Energy Radiation 413Site-Directed Mutagenesis 414

Knockout Genes and Transgenes 415Transposable Genetic Elements 416

Insertion Sequences 416Bacterial Transposons 416The Ac-Ds System in Maize 417Other Mobile Genetic Elements in Plants:Mendel Revisited 418Copia and P Elements in Drosophila 419Transposable Elements in Humans 420

GENETICS, TECHNOLOGY, AND SOCIETYP Element Transposons: New Age Mutagens 421

15 Recombinant DNA Technology 428Recombinant DNA Technology: An Overview 429Making Recombinant DNA 429

Restriction Enzymes 429Vectors. 431Plasmid Vectors 431Lambda and Ml3 Bacteriophage Vectors 434Cosmid Vectors and Shuttle Vectors 43 5Bacterial Artificial Chromosomes 436

Cloning DNA in E. coli 437Cloning in Eukaryotic Hosts 438

Yeast Vectors 439Yeast Artificial Chromosomes 439

Constructing DNA Libraries 439Genomic Libraries 439Chromosome-Specific Libraries 440cDNA Libraries 441

Identifying Specific Cloned Sequences 442Probes to Screen for Specific Clones 442Screening a Library 443Chromosome Walking 443

Methods for the Analysis of Cloned Sequences 445Restriction Mapping 445Southern and Northern Blots 447

DNA Sequencing 449PCR Analysis 450

Transferring DNA in Eukaryotes 452Plant Cells 452Mammalian Cells 452

GENETICS, TECHNOLOGY, AND SOCIETYReporter Gene Technology:Tracking Gene Expression 454

16 Applications of Recombinant DNATechnology 461Mapping Human Genes 462

RFLPs as Genetic Markers 462Using RFLPs to Make Linkage Maps 463Positional Cloning: The Gene forNeurofibromatosis 464Candidate Genes: The Gene for MarfanSyndrome 465

Diagnosing and Screening Genetic Disorders 466Deletions in Thalassemia 466Sickle-Cell Anemia and Prenatal Genotyping 466Allele-Specific Nucleotides and GeneticScreening 468

Animal Models of Human Genetic Disease:Knockout Mice 469Gene Therapy 471

Severe Combined Immunodeficiency (SCID) 471New Vectors and Target-Cell Strategies 472

DNA Fingerprints 473Minisatellites and VNTRs 473Forensic Applications 474

Genome Analysis 474Model Organisms: The E. coli Project 475The Drosophila Genome 475Human Genome Project 476After the Genome Projects 477

Biotechnology 478 •Insulin Production 478Pharmaceutical Products in Animal Hosts 479Herbicide-Resistant Crop Plants 480Transgenic Plants and Vaccines 480

GENETICS, TECHNOLOGY, AND SOCIETYPCR and DNA Fingerprinting in Forensics:The Case of the Telltale Palo Verde 482

1/ Genomic Organization of DNA 490Viral and Bacterial Chromosomes 491Supercoiling and Circular DNA 492

CONTENTS XIX

Mitochondrial and Chloroplast DNA 494Molecular Organization and Function ofMitochondrial DNA 495Molecular Organization and Function of ChloroplastDNA 496

Organization of DNA in Chromatin 497Nucleosome Structure 497Nuclear Scaffolds 500Heterochromatin 500Satellite DNA and Repetitive DNA 500Chromosome Banding 502

Organization of the Eukaryotic Genome 502Eukaryotic Genomes and the C Value Paradox 503Repetitive DNA: Centromeres and Telomeres" 503Repetitive DNA: SINEs, LINEs, and VNTRs 506Eukaryotic Gene Structure 507 •Exon Shuffling and Protein Domains 508Multigene Families: The alpha- and beta-GlobinGenes 509The Histone Gene Family 511Tandem Repeat Families: rRNA Genes 512

Genomic Analysis 512The Genome Project 513The Minimal Coding Set 514

PART THREEADVANCED TOPICS IN GENETICANALYSIS 521

18 Regulation of Gene Expression inBacteria and Phages 522Genetic Regulation in Prokaryotes:An Overview 523Lactose Metabolism in E. coli: An Inducible GeneSystem 523

Structural Genes 524The Discovery of Regulatory Mutations 524

The Operon Model: Negative Control 525Genetic Proof of the Operon Model 526Isolation of the Repressor 528Crystallographic Analysis of the Repressor 528The Catabolite Activating Protein (CAP): PositiveControl of the lac Operon 528

The ara Regulator Protein—Positive and NegativeControl 529

Tryptophan Operon in E. coli: A Repressible GeneSystem 529

Evidence for and Concerning the trp Operon 531The Attenuator 532

Genetic Regulation in Phage Lambda: Lysogeny orLysis? 534Phage Transcription during Lysis 536

GENETICS, TECHNOLOGY, AND SOCIETY ;Antisense Oligonudeotides:Attacking the Messenger 538 • '

19 Regulation of Gene Expression inEukaryotes 544Eukaryotic Gene Regulation: An Overview 545Regulatory Elements and Eukaryotic Genes 545

Promoters 546Enhancers 546

Transcription Factors Bind to Promoters andEnhancers 548

Genetic Analysis of Transcription Factors 548Structural Motifs of Transcription Factors 549Assembling the Transcription Complex 551How Are Transcription Factors Controlled? 551

Genomic Alterations and Gene Expression 554DNAMethylation 554Gene Amplification 556

Posttranscriptional Regulation of GeneExpression 558

Alternative Processing Pathways for mRNA 558Controlling mRNA Stability 560

GENETICS, TECHNOLOGY, AND SOCIETYEntrapping Genes That RegulateDevelopment 562

20 Developmental Genetics 567Developmental Concepts 568The Variable Gene Activity Theory 568Differential Transcription in Development:Prokaryotes 568

XX CONTENTS

Differential Transcription in Development:Eukaryotes 569

Genome Equivalence 570Binary Switch Genes 572 •

Genetics of Embryonic Development inDrosophila 573

Overview of Drosophila Development 574Genetic Analysis of Embryogenesis 576

Maternal-Effect Genes and the Basic Body Plan inDrosophila 577

Formation of the Anterior-Posterior Axis 578The Posterior and Terminal Gene Sets 578

Zygotic Genes and Segment Formation 580Gap Genes 580Pair-Rule Genes 580Segment-Polarity Genes 581

Selector Genes 581Cell-Cell Interactions in C. elegansDevelopment 584

Overview of C. elegans Development 584Genetic Analysis of Vulva Formation 585

21 Genetics and Cancer 591The Cell Cycle and Cancer 592

The Cell Cycle 592Checkpoints and Control of the Cell Cycle 593Cell-Cycle Regulation and Cancer 594

Genes and Cancer 594Genes That Predispose to Cancer 594How Many Mutations Are Needed? 595

Tumor Suppressor Genes 595Retinoblastoma (RB) 596Wilms Tumor 597Breast Cancer 598The p53 Gene and the Cell Cycle 598

Oncogenes 599Rous Sarcoma Virus and Oncogenes 599Mutations and Oncogenes 599Oncogenes and Gene Expression 600

Metastasis Is Genetically Controlled 601The Spread of Cancer Cells 601Metastasis and Abnormal Gene Regulation 602

A Genetic Model for Colon Cancer 603Colon Cancer Develops in Stages 603Genetic and Environmental Factors in ColonCancer 604

Genomic Changes and Cancer 604Chromosome Rearrangements and Cancer 604

Translocations and Hybrid Genes 604Genomic Instability and Cancer 605

Cancer and Environmental Agents 606Hepatitis B and Cancer 606Environmental Agents 607

GENETICS, TECHNOLOGY, AND SOCIETYThe Cancer-Yeast Connection:The Seattle Project 608

22 Genetic Basis of the ImmuneResponse 614Components of the Immune System 615

Cells of the Immune System 615The Immune Response 616

Antibody-Mediated Immunity 616Cell-Mediated Immunity 618Immunological Memory and Immunization 619

Genetic Diversity in the Immune System 619Antibodies 619Theories of Antibody Formation 620Organization of the Immunoglobulin Genes 621Organization of T-Cell Receptors 62 3Recombination in the Immune System 624

Blood Groups 624ABO System 624Rh Incompatibility 624

The HLA System 626HLA Genes 626Organ and Tissue Transplantation 627HLA and Disease 627

Disorders of the Immune System 62 8The Genetics of Immunodeficiency 628Acquired Immunodeficiencies: DiGeorge Syndromeand AIDS 629Autoimmunity 631

GENETICS, TECHNOLOGY, AND SOCIETYWhy Is There Still No Effective Vaccine againstAIDS? 632

23 The Genetics of Behavior 637The Methodology of Behavior Genetics 638

The Comparative Approach 638Artificial Selection 639Analysis of Single Gene Effects 641

Genetic Analysis of Behavior in Drosophila 646Mosaics 647

CONTENTS

Neurogenetics 650Learning in Drosophila 651

Human Behavioral Genetics 652Single Genes 652Multifactorial Traits 653

GENETICS, TECHNOLOGY, AND SOCIETY' Coining to Terms with the Heritability oflQ 654

24 Population Genetics 659Populations and Gene Pools 660Calculating Allele Frequencies 660The Hardy-Weinberg Law 660

Assumptions for the Hardy-Weinberg Law 661Testing for Equilibrium 662

Extensions of the Hardy-Weinberg Law 663X-Linked Genes 664Multiple Alleles 664

Using the Hardy-Weinberg Law: CalculatingHeterozygote Frequency 665Factors That Alter Allele Frequencies inPopulations 666

Mutation 666Migration 667Natural Selection 668Fitness and Selection 670Selection in Natural Populations 671Genetic Drift 672Inbreeding 673Nonrandom Mating 674Genetic Effects of Inbreeding 675

GENETICS, TECHNOLOGY, AND SOCIETY ;The Failure of the Eugenics Movement:What Did We Learn? 616

25 Genetics and Evolution 681Wallace, Darwin and the Origin of Species 682Models of Speciation 682

Allopatric Speciation 683Sympatric Speciation 683Statispatric Speciation 684

Isolating Mechanisms 684The Rate of Speciation 684Measuring Genetic Variation 688

Inbreeding Depression 688Protein Polymorphisms 688Variations in Nucleotide Sequence 689

Evolution and Genetic Variation: A Dilemma 690

Neutralists and Variation 690Selectionists and Variation 690

Formation of Species 691Using Molecular Techniques to StudyEvolution 694

Measuring the Genetic Distance between Species 694Protein Evolution 695The Molecular Clock 696Phylogenetic Trees 696Molecular Studies on Human Evolution 697

; GENETICS, TECHNOLOGY, AND SOCIETY; DNA from Fossils: The Quest for DinosaurGenes 698

APPENDIX A: Experimental Methods A-lAPPENDIX B: Glossary B-lAPPENDIX C: Solutions to Selected Even-Numbered

Problems and Discussion Questions C-1CREDITS CR-1INDEX 1-1