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CONCEPTS
OF
TIC
Fifth Edition
WILLIAM S. KLUG
The College ofNew Jersey
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MICHAEL R. CUMMINGS
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University ofIllinois, Chicago
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An Introduction to Genetics, 1
PART ONE HEREDITY AND THE PHENOTYPE, 17
2
3
4
5
6
7
8
9
PART TWO
10
n
12
13
14
15
16
17
Cell Division and Chromosomes, 18
Mendelian Genetics, 50
Modification of Mendelian Ratios, 79
Linkage, Crossing Over, and Chromosome Mapping, 115
Recombination and Mapping in Bacteria and Bacteriophages, 149
Extensions of Genetic Analysis, 180
Extranuclear Inheritance, 208
Chromosome Variation and Sex Determination, 221
MOLECULAR BASIS OF HEREDITY, 261
Structure and Analysis of DNA and RNA, 262
DNA Replication and Recombination, 298
Storage and Expression of Genetic Information, 324
Proteins: The End Product of Genetic Expression, 364
Gene Mutation, DNA Repair, and Transposable Elements, 389
Recombinant DNA Technology, 428
Applications of Recombinant DNA Technology, 461
Genomic Organization of DNA, 490
PART THREE ADVANCED TOPICS IN GENETIC ANALYSIS, 521
18
19
20
21
22
23
24
25
APPENDIX A:
APPENDIX B:
APPENDIX C:
CREDITS
INDEX
Regulation of Gene Expression in Bacteria and Phages, 522
Regulation of Gene Expression in Eukaryotes, 544
Developmental Genetics, 567
Genetics and Cancer, 591
Genetic Basis of the Immune Response, 614
The Genetics of Behavior, 637
Population Genetics, 659
Genetics and Evolution, 681
Experimental Methods A-1
Glossary B-l
Solutions to Selected Even-Numbered Problems and Discussion Questions C-l
CR-1
1-1
N
1 An Introduction to Genetics, 1
The Historical Context of Genetics 2
Prehistoric Domestication of Animals and Cultivation
of Plants 2
The Greek Influence: Hippocrates and Aristotle 2
The Dawn of Modern Biology: 1600-1850 3
Darwin: The Gap in His Theory of Evolution 4
Mendel: An Experimental Biologist 5
Basic Concepts of Genetics 6
Investigative Approaches in Genetics 9
Genetics and Society 10
y
Eugenics: The Misguided Application of Science 10
Soviet Science: The Lysenko Affair 11
GENETICS, TECHNOLOGY, AND SOCIETY
A New Era in Plant Genetics: The Flavr Saw
Tomato and Edible Vaccines 12
N
Prometaphase and Metaphase 27
Anaphase 27
Telophase 29
Genetic Regulation of the Cell Cycle 30
Meiosis and Sexual Reproduction 31
An Overview of Meiosis 32
The First Meiotic Division: Prophase 132
Metaphase, Anaphase, and Telophase 133
Spermatogenesis and Oogenesis 36
The Significance of Meiosis 36
The Cytological Origin of the Mitotic and Meiotic
Chromosome 39
The Synaptonemal Complex 40
Specialized Chromosomes 42
Polytene Chromosomes 42
Lampbrush Chromosomes 43
Genetic Advances in Agriculture and Medicine 12
Mendelian Genetics 50
PART ONE
HEREDITY AND THE PHENOTYPE 17
2 Cell Division and Chromosomes 18
Cell Structure 19
Cell Boundaries 19
The Nucleus 20
The Cytoplasm and Organelles 21
Homologous Chromosomes, Haploidy, and
Diploidy 22
Mitosis and Cell Division 2 5
Interphase and the Cell Cycle 25
Prophase 26
Gregorjohann Mendel 51
Mendel's Experimental Approach 51
The Monohybrid Cross 51
Mendel's First Three Postulates 53
Modern Genetic Terminology 54
Mendel's Analytical Approach 55
Punnett Squares 55
The Test Cross: One Character 55
The Dihybrid Cross 56
Mendel's Fourth Postulate: Independent
Assortment 56
The Test Cross: Two Characters 57
The Trihybrid Cross 59
The Forked-Line Method, or Branch Diagram 59
The Rediscovery of Mendel's Work 61
The Rebirth of Mendelian Genetics 61
Unit Factors, Genes, and Homologous
Chromosomes 62
Independent Assortment and Genetic Variation 63
Probability and Genetic Events 63
The Product Law and Sum Law 63
Conditional Probability 64
The Binomial Theorem 65
Evaluating Genetic Data: Chi-Square Analysis 66
Human Pedigrees 69
Xlll
XIV
CONTENTS
4 Modification of Mendelian Ratios 79
Potential Function of an Allele 80
Symbols for Alleles 80
Incomplete, or Partial, Dominance 81
Codominance 82
Multiple Alleles 83
The ABO Blood Groups 83
The A and B Antigens 83
The Bombay Phenotype 85
The Secretor Locus 85
The Rh Antigens 85
The white Locus in Drosophila 86
Lethal Alleles 86
Combinations of Two Gene Pairs 88
Gene Interaction: Discontinuous Variation 89
Epistasis 89
Novel Phenotypes 93
Other Modified Dihybrid Ratios 95
Gene Interaction: Continuous Variation 95
Quantitative Inheritance: Polygenes 95
Calculating the Number of Polygenes 99
The Significance of Polygenic Control 100
Genes on the X Chromosome: X-Linkage 100
X-Linkage in Drosophila 100
X-Linkage in Humans 102
Sex-Limited and Sex-Influenced Inheritance 103
GENETICS, TECHNOLOGY, AND SOCIETY
The Uncertain Genetic Fate of Purebred Dogs 104
5 Linkage, Crossing Over, and
Chromosome Mapping 115
Linkage versus Independent Assortment 116
The Linkage Ratio 116
Incomplete Linkage, Crossing Over, and
Chromosome Mapping 118
Morgan and Crossing Over 119
Sturtevant and Mapping 119
Single Crossovers 121
Multiple Crossovers 121
Three-Point Mapping in Drosophila 122
Determining the Gene Sequence 124
A Mapping Problem in Maize 126
Interference and the Coefficient of Coincidence 129
The Inaccuracy of Mapping Experiments 130
The Genetic Map of Drosophila 131
Other Aspects of Genetic Exchange 131
Crossing Over in the Four-Strand Stage 132
Cytological Evidence for Crossing Over 134
The Mechanism of Crossing Over 135
Mitotic Recombination 136
Sister Chromatid Exchanges 137
Somatic Cell Hybridization and Human
Chromosome Maps 138
Did Mendel Encounter Linkage? 140
Why Didn 't Gregor Mendel Find Linkage? 141
6 Recombination and Mapping in
Bacteria and Bacteriophages 149
Bacterial Mutation and Growth 150
Genetic Recombination in Bacteria:
Conjugation 151
F + and F~ Bacteria 152
Hfr Bacteria and Chromosome Mapping 154
Recombination in F + X F~ Matings:
A Reexamination 156
The F' State and Merozygotes 157
The Rec Proteins and Bacterial
Recombination 158
Plasmids 158
Bacterial Transformation 160
Transformation and Mapping 161
The Genetic Study of Bacteriophages 162
Phage T4 Infection and Reproduction 162
The Plaque Assay 164
Lysis and Lysogeny 165
Transduction: Virus-Mediated Bacterial DNA
Transfer 165
The Lederberg-Zinder Experiment 165
The Nature of Transduction 166
y
Mapping and Specialized Transduction 167
Mutation and Recombination in Viruses 168
Genetic Exchange between Bacterial Viruses 168
Intragenic Recombination in Phage T 4 169
The rll Locus of Phage T4 170
Complementation by rll Mutations 170
Recombinational Analysis 172
Deletion Testing of the rll Locus 172
The rll Gene Map 174
7 Extensions of Genetic Analysis 180
Phenotypic Expression 181
Penetrance and Expressivity 181
CONTENTS
Genetic Background: Suppression and Position
Effects 182
Temperature Effects 182
Nutritional Effects 183
Onset of Genetic Expression 184
Genetic Anticipation 184
Genomic (Parental) Imprinting 185
Continuous Variation and Polygenes 186
Continuous versus Discontinuous Variation 186
Mapping Quantitative Trait Loci 187
Analysis of Polygenic Traits 188
The Mean 189
Variance 189
Standard Deviation 190
Standard Error of the Mean 190
Analysis of a Quantitative Character 190
Heritability 192
Broad-Sense Heritability 192
Narrow-Sense Heritability 192
Artificial Selection 193
Twin Studies in Humans 193
The Use of Haploid Organisms in Linkage and
Mapping Studies 194
Gene-to-Centromere Mapping 195
Ordered versus Unordered Tetrad Analysis 196
Linkage and Gene Mapping in Haploid
Organisms 197
GENETICS, TECHNOLOGY, AND SOCIETY
Preserving Plant Germplasm: The Key to the
Future ofAgriculture 200
8 Extranuclear Inheritance 208
Maternal Effect 209
Ephestia Pigmentation 209
Limnaea Coiling 209
Embryonic Development in Drosophila 210
Organelle Heredity 211
Chloroplasts: Variegation in Four O'Clock Plants 211
Iojap in Maize 211
Chlamydomonas Mutations 212
Mitochondria: poky in Neurospora 213
Petite in Saccharomyces 213
Mitochondrial DNA and Human Diseases 214
Infectious Heredity 216
Kappa in Paramecium 216
Infective Particles in Drosophila 217
XV
9 Chromosome Variation and Sex
Determination 221
Variation in Chromosome Number:
An Overview 222
The Diploid Chromosome Number in
Humans 222
Chromosomes, Sex Differentiation, and Sex
Determination in Humans, 222
Klinefelter and Turner Syndromes 223
47,XXX Syndrome 223
47,XYY Condition 223
Sexual Differentiation in Humans 225
The Y Chromosome and Male Development 226
Sex Ratio in Humans 226
Dosage Compensation in Humans 227
Barr Bodies 227
The Lyon Hypothesis 228
The Mechanism of Inactivation 229
Chromosome Composition and Sex Determination
in Drosophila 230
Dosage Compensation in Drosophila 232
Drosophila Mosaics 233
Aneuploidy 234
Monosomy 234
Partial Monosomy: Cri-du-Chat Syndrome 234
Trisomy 235
Down Syndrome 236
Patau Syndrome 237
Edwards Syndrome 237
Viability in Human Aneuploidy 238
Polyploidy and Its Origins 238
Autopolyploidy 239
Allopolyploidy 240
y
Endopolyploidy 242
~
Variation in Chromosome Structure and
Arrangement: An Overview 243
Deletions 243
Duplications 244
Gene Redundancy and Amplification: Ribosomal RNA
Genes 244
The Bar Eye Mutation in Drosophila 245
The Role of Gene Duplication in Evolution 246
Inversions 247
Consequences of Inversions during Gamete
Formation 248
Position Effects of Inversions 248
Evolutionary Consequences of Inversions 250
XVI
CONTENTS
Translocations 250
Translocations in Humans: Familial Down
Syndrome 251
Fragile Sites in Humans 252
Fragile X Syndrome (Martin-Bell Syndrome) 253
FH1TGene and Human Lung Cancer 253
Other Forms of DNA 283
The Structure of RNA 283
Analysis of Nucleic Acids 285
Absorption of Ultraviolet Light (UV) 285
Sedimentation Behavior 285
Denaturation and Renaturation of Nucleic Acids 287
Molecular Hybridization 288
Reassociation Kinetics and Repetitive DNA 288
Electrophoresis of Nucleic Acids 291
11 DNA Replication and
Recombination 298
The Mode of DNA Replication 299
PART TWO
MOLECULAR BASIS OF HEREDITY 261
10 Structure and Analysis of DNA
and RNA 262
Characteristics of the Genetic Material 263
The Genetic Material: 1900-1944 264
Evidence Favoring DNA as the Genetic Material in
Bacteria and Bacteriophages 264
Transformation Studies 265
The Hershey-Chase Experiment 268
Transfection Experiments 269
Indirect Evidence Favoring DNA in
Eukaryotes 271
Distribution of DNA 271
Mutagenesis 271
Direct Evidence for DNA: Eukaryotic Data 271
RNA as the Genetic Material 272
Nucleic Acid Chemistry 273
Nucleotides: Building Blocks of Nucleic Acids 274
Nucleoside Diphosphates and Triphosphates 275
Polynucleotides 275
The Structure of DNA 277
Base Composition Studies 277
X-Ray Diffraction Analysis 277
The Watson-Crick Model 278
Molecular Structure ofNucleic Acids: A Structure for
Deoxyribose Nucleic Acid 280
The Meselson-Stahl Experiment 300
Semiconservative Replication in Eukaryotes 300
Origins, Forks, and Units of Replication 303
Synthesis of DNA in Microorganisms 303
DNA Polymerase I 304
Fidelity of Synthesis 305
Synthesis of Biologically Active DNA 306
DNA Polymerase II and III 308
DNA Synthesis: A Model 309
Unwinding the DNA Helix 309
Initiation of Synthesis 310
Continuous and Discontinuous DNA Synthesis 311
Concurrent Synthesis on the Leading and Lagging
Strands 311
Proofreading 312
/
Summary of DNA Synthesis 313
Genetic Control of Replication 313
Eukaryotic DNA Synthesis 315
DNA Synthesis at the Ends of Linear
Chromosomes 315
DNA Recombination 317
Gene Conversion 317
12 Storage and Expression of Genetic
Information 324
An Overview of the Genetic Code 325
Early Thinking about the Code 325
The Code: Further Developments 326
The Study of Frameshift Mutations 326
Deciphering the Code: Initial Studies 327
Nirenberg and Matthaei's Homopolymer Codes 328
The Use of Mixed Copolymers 328
The Triplet Binding Technique 330
The Use of Repeating Copolymers 331
CONTENTS
The Coding Dictionary 332
Degeneracy and Wobble, and Order in the Code 332
Initiation, Termination, and Suppression 333
Confirmation of Code Studies: Phage MS2 334
Universality of the Code 334
Reading the Code: The Case of Overlapping
Genes 335
Expression of Genetic Information:
An Overview 336
Transcription: RNA Synthesis 336
Experimental Evidence for the Existence of
mRNA 337
RNA Polymerase 337
Promoters, Template Binding, and the Sigma
Subunit 338
The Synthesis of RNA 338
Visualization of Transcription 341
Transcription in Eukaryotes 341
Eukaryotic Promoters, Enhancers, and Transcription
Factors 341
Heterogeneous Nuclear RNA and Its Processing:
Caps and Tails 342
Intervening Sequences and Split Genes 343
Splicing Mechanisms: Autocatalytic RNAs 345
Splicing Mechanisms: The Spliceosome 346
RNA Editing 346
Translation: Components Necessary for Protein
Synthesis 347
Ribosomal Structure 347
tRNA Structure 349
Charging tRNA 350
Translation: The General Process 351
Initiation (Steps 1-3) 351
Elongation (Steps 4-9) 354
Termination (Steps 10-11) 354
Polyribosomes 355
Translation in Eukaryotes 355
GENETICS, TECHNOLOGY, AND SOCIETY
Genetic Testing Dilemmas: Sickle-Cell Anemia
and Breast Cancer 356
13 Proteins: The End Product of Gene
Expression 364
Garrod and Bateson: Inborn Errors of
Metabolism 365
Phenylketonuria 366
The One-Gene: One-Enzyme Hypothesis 366
Beadle and Ephrussi: Drosophila Eye Pigments 366
XVII
Beadle and Tatum: Neurospora Mutants 368
Genes and Enzymes: Analysis of Biochemical
Pathways 370
One-Gene: One-Protein/
One-Gene: One-Polypeptide 370
Sickle-Cell Anemia 371
Human Hemoglobins 373
Colinearity 373
Protein Structure and Function 374
Protein Structure 374
Chaperones and Protein Folding 377
Posttranslational Modification and Protein
Targeting 378
'
.
Protein Function 379
Protein Structure and Function: The Collagen
Fiber 380
The Genetics of Collagen 380
GENETICS, TECHNOLOGY, AND SOCIETY
Prions, Mad Cows, and Heresies 3 82
14 Gene Mutation, DNA Repair, and
Transposable Elements 389
Random versus Adaptive Mutations 390
The Luria-Delbruck Fluctuation Test 390
Adaptive Mutation in Bacteria 391
Classification of Mutations 392
Spontaneous versus Induced Mutations 392
Gametic versus Somatic Mutations 393
Other Categories of Mutation 393
Detection of Mutations 394
Detection in Bacteria and Fungi 394
Detection in Drosophila 394
Detection in Plants 396
Detection in Humans 397
^~">ntaneous Mutation Rate 397
Moit^clar Basis of Mutation 400
Tautomeric Shifts 400
Base Analogues 402
Alkylating Agents 402
Acridine Dyes and Frameshift Mutations 403
Apurinic Sites and Other Lesions 405
Ultraviolet Radiation, Thymine Dimers, and the SOS
Response 406
Case Studies of Mutations in Humans 407
ABO Blood Types versus Muscular Dystrophy 407
Trinucleotide Repeats in Fragile-X Syndrome,
Myotonic Dystrophy, and Huntington Disease 408
Detection of Mutagenicity: The Ames Test 409
XVlll
CONTENTS
Repair of DNA 409
UV Radiation, Thymine Dimers, and
Photoreactivation Repair 409
Excision Repair 410
Proofreading and Mismatch Repair 411
The SOS Response: Recombinational Repair 411
UV Radiation and Human Skin Cancer:
Xeroderma Pigmentosum 412
Somatic Cell Hybridization, XP, and Excision
Repair 413
High-Energy Radiation 413
Site-Directed Mutagenesis 414
Knockout Genes and Transgenes 415
Transposable Genetic Elements 416
Insertion Sequences 416
Bacterial Transposons 416
The Ac-Ds System in Maize 417
Other Mobile Genetic Elements in Plants:
Mendel Revisited 418
Copia and P Elements in Drosophila 419
Transposable Elements in Humans 420
GENETICS, TECHNOLOGY, AND SOCIETY
P Element Transposons: New Age Mutagens 421
15 Recombinant DNA Technology 428
Recombinant DNA Technology: An Overview 429
Making Recombinant DNA 429
Restriction Enzymes 429
Vectors. 431
Plasmid Vectors 431
Lambda and Ml3 Bacteriophage Vectors 434
Cosmid Vectors and Shuttle Vectors 43 5
Bacterial Artificial Chromosomes 436
Cloning DNA in E. coli 437
Cloning in Eukaryotic Hosts 438
Yeast Vectors 439
Yeast Artificial Chromosomes 439
Constructing DNA Libraries 439
Genomic Libraries 439
Chromosome-Specific Libraries 440
cDNA Libraries 441
Identifying Specific Cloned Sequences 442
Probes to Screen for Specific Clones 442
Screening a Library 443
Chromosome Walking 443
Methods for the Analysis of Cloned Sequences 445
Restriction Mapping 445
Southern and Northern Blots 447
DNA Sequencing 449
PCR Analysis 450
Transferring DNA in Eukaryotes 452
Plant Cells 452
Mammalian Cells 452
GENETICS, TECHNOLOGY, AND SOCIETY
Reporter Gene Technology:
Tracking Gene Expression 454
16 Applications of Recombinant DNA
Technology 461
Mapping Human Genes 462
RFLPs as Genetic Markers 462
Using RFLPs to Make Linkage Maps 463
Positional Cloning: The Gene for
Neurofibromatosis 464
Candidate Genes: The Gene for Marfan
Syndrome 465
Diagnosing and Screening Genetic Disorders 466
Deletions in Thalassemia 466
Sickle-Cell Anemia and Prenatal Genotyping 466
Allele-Specific Nucleotides and Genetic
Screening 468
Animal Models of Human Genetic Disease:
Knockout Mice 469
Gene Therapy 471
Severe Combined Immunodeficiency (SCID) 471
New Vectors and Target-Cell Strategies 472
DNA Fingerprints 473
Minisatellites and VNTRs 473
Forensic Applications 474
Genome Analysis 474
Model Organisms: The E. coli Project 475
The Drosophila Genome 475
Human Genome Project 476
After the Genome Projects 477
Biotechnology 478 •
Insulin Production 478
Pharmaceutical Products in Animal Hosts 479
Herbicide-Resistant Crop Plants 480
Transgenic Plants and Vaccines 480
GENETICS, TECHNOLOGY, AND SOCIETY
PCR and DNA Fingerprinting in Forensics:
The Case of the Telltale Palo Verde 482
1/ Genomic Organization of DNA 490
Viral and Bacterial Chromosomes 491
Supercoiling and Circular DNA 492
CONTENTS
Mitochondrial and Chloroplast DNA 494
Molecular Organization and Function of
Mitochondrial DNA 495
Molecular Organization and Function of Chloroplast
DNA 496
Organization of DNA in Chromatin 497
Nucleosome Structure 497
Nuclear Scaffolds 500
Heterochromatin 500
Satellite DNA and Repetitive DNA 500
Chromosome Banding 502
Organization of the Eukaryotic Genome 502
Eukaryotic Genomes and the C Value Paradox 503
Repetitive DNA: Centromeres and Telomeres" 503
Repetitive DNA: SINEs, LINEs, and VNTRs 506
Eukaryotic Gene Structure 507 •
Exon Shuffling and Protein Domains 508
Multigene Families: The alpha- and beta-Globin
Genes 509
The Histone Gene Family 511
Tandem Repeat Families: rRNA Genes 512
Genomic Analysis 512
The Genome Project 513
The Minimal Coding Set 514
PART THREE
ADVANCED TOPICS IN GENETIC
ANALYSIS 521
18 Regulation of Gene Expression in
Bacteria and Phages 522
Genetic Regulation in Prokaryotes:
An Overview 523
Lactose Metabolism in E. coli: An Inducible Gene
System 523
Structural Genes 524
The Discovery of Regulatory Mutations 524
XIX
The Operon Model: Negative Control 525
Genetic Proof of the Operon Model 526
Isolation of the Repressor 528
Crystallographic Analysis of the Repressor 528
The Catabolite Activating Protein (CAP): Positive
Control of the lac Operon 528
The ara Regulator Protein—Positive and Negative
Control 529
Tryptophan Operon in E. coli: A Repressible Gene
System 529
Evidence for and Concerning the trp Operon 531
The Attenuator 532
Genetic Regulation in Phage Lambda: Lysogeny or
Lysis? 534
Phage Transcription during Lysis 536
GENETICS, TECHNOLOGY, AND SOCIETY ;
Antisense Oligonudeotides:
Attacking the Messenger 538
•
'
19 Regulation of Gene Expression in
Eukaryotes 544
Eukaryotic Gene Regulation: An Overview 545
Regulatory Elements and Eukaryotic Genes 545
Promoters 546
Enhancers 546
Transcription Factors Bind to Promoters and
Enhancers 548
Genetic Analysis of Transcription Factors 548
Structural Motifs of Transcription Factors 549
Assembling the Transcription Complex 551
How Are Transcription Factors Controlled? 551
Genomic Alterations and Gene Expression 554
DNAMethylation 554
Gene Amplification 556
Posttranscriptional Regulation of Gene
Expression 558
Alternative Processing Pathways for mRNA 558
Controlling mRNA Stability 560
GENETICS, TECHNOLOGY, AND SOCIETY
Entrapping Genes That Regulate
Development 562
2 0 Developmental Genetics 567
Developmental Concepts 568
The Variable Gene Activity Theory 568
Differential Transcription in Development:
Prokaryotes 568
XX
CONTENTS
Differential Transcription in Development:
Eukaryotes 569
Genome Equivalence 570
Binary Switch Genes 572 •
Genetics of Embryonic Development in
Drosophila 573
Overview of Drosophila Development 574
Genetic Analysis of Embryogenesis 576
Maternal-Effect Genes and the Basic Body Plan in
Drosophila 577
Formation of the Anterior-Posterior Axis 578
The Posterior and Terminal Gene Sets 578
Zygotic Genes and Segment Formation 580
Gap Genes 580
Pair-Rule Genes 580
Segment-Polarity Genes 581
Selector Genes 581
Cell-Cell Interactions in C. elegans
Development 584
Overview of C. elegans Development 584
Genetic Analysis of Vulva Formation 585
21 Genetics and Cancer 591
The Cell Cycle and Cancer 592
The Cell Cycle 592
Checkpoints and Control of the Cell Cycle 593
Cell-Cycle Regulation and Cancer 594
Genes and Cancer 594
Genes That Predispose to Cancer 594
How Many Mutations Are Needed? 595
Tumor Suppressor Genes 595
Retinoblastoma (RB) 596
Wilms Tumor 597
Breast Cancer 598
The p53 Gene and the Cell Cycle 598
Oncogenes 599
Rous Sarcoma Virus and Oncogenes 599
Mutations and Oncogenes 599
Oncogenes and Gene Expression 600
Metastasis Is Genetically Controlled 601
The Spread of Cancer Cells 601
Metastasis and Abnormal Gene Regulation 602
A Genetic Model for Colon Cancer 603
Colon Cancer Develops in Stages 603
Genetic and Environmental Factors in Colon
Cancer 604
Genomic Changes and Cancer 604
Chromosome Rearrangements and Cancer 604
Translocations and Hybrid Genes 604
Genomic Instability and Cancer 605
Cancer and Environmental Agents 606
Hepatitis B and Cancer 606
Environmental Agents 607
GENETICS, TECHNOLOGY, AND SOCIETY
The Cancer-Yeast Connection:
The Seattle Project 608
22 Genetic Basis of the Immune
Response 614
Components of the Immune System 615
Cells of the Immune System 615
The Immune Response 616
Antibody-Mediated Immunity 616
Cell-Mediated Immunity 618
Immunological Memory and Immunization 619
Genetic Diversity in the Immune System 619
Antibodies 619
Theories of Antibody Formation 620
Organization of the Immunoglobulin Genes 621
Organization of T-Cell Receptors 62 3
Recombination in the Immune System 624
Blood Groups 624
ABO System 624
Rh Incompatibility 624
The HLA System 626
HLA Genes 626
Organ and Tissue Transplantation 627
HLA and Disease 627
Disorders of the Immune System 62 8
The Genetics of Immunodeficiency 628
Acquired Immunodeficiencies: DiGeorge Syndrome
and AIDS 629
Autoimmunity 631
GENETICS, TECHNOLOGY, AND SOCIETY
Why Is There Still No Effective Vaccine against
AIDS? 632
23 The Genetics of Behavior 637
The Methodology of Behavior Genetics 638
The Comparative Approach 638
Artificial Selection 639
Analysis of Single Gene Effects 641
Genetic Analysis of Behavior in Drosophila 646
Mosaics 647
CONTENTS
Neurogenetics 650
Learning in Drosophila 651
Human Behavioral Genetics 652
Single Genes 652
Multifactorial Traits 653
GENETICS, TECHNOLOGY, AND SOCIETY
' Coining to Terms with the Heritability oflQ 654
24 Population Genetics 659
Populations and Gene Pools 660
Calculating Allele Frequencies 660
The Hardy-Weinberg Law 660
Assumptions for the Hardy-Weinberg Law 661
Testing for Equilibrium 662
Extensions of the Hardy-Weinberg Law 663
X-Linked Genes 664
Multiple Alleles 664
Using the Hardy-Weinberg Law: Calculating
Heterozygote Frequency 665
Factors That Alter Allele Frequencies in
Populations 666
Mutation 666
Migration 667
Natural Selection 668
Fitness and Selection 670
Selection in Natural Populations 671
Genetic Drift 672
Inbreeding 673
Nonrandom Mating 674
Genetic Effects of Inbreeding 675
GENETICS, TECHNOLOGY, AND SOCIETY ;
The Failure of the Eugenics Movement:
What Did We Learn? 616
25 Genetics and Evolution 681
Wallace, Darwin and the Origin of Species 682
Models of Speciation 682
Allopatric Speciation 683
Sympatric Speciation 683
Statispatric Speciation 684
Isolating Mechanisms 684
The Rate of Speciation 684
Measuring Genetic Variation 688
Inbreeding Depression 688
Protein Polymorphisms 688
Variations in Nucleotide Sequence 689
Evolution and Genetic Variation: A Dilemma 690
Neutralists and Variation 690
Selectionists and Variation 690
Formation of Species 691
Using Molecular Techniques to Study
Evolution 694
Measuring the Genetic Distance between Species 694
Protein Evolution 695
The Molecular Clock 696
Phylogenetic Trees 696
Molecular Studies on Human Evolution 697
; GENETICS, TECHNOLOGY, AND SOCIETY
; DNA from Fossils: The Quest for Dinosaur
Genes 698
APPENDIX A: Experimental Methods A-l
APPENDIX B: Glossary B-l
APPENDIX C: Solutions to Selected Even-Numbered
Problems and Discussion Questions C-1
CREDITS
CR-1
INDEX
1-1