iGenetics: A molecular approach

Cover......Page 1
Title Page......Page 3
Copyright Page......Page 2
Brief Contents......Page 5
Contents......Page 7
Preface......Page 14
Acknowledgments......Page 19
Classical and Modern Genetics......Page 23
Basic and Applied Research......Page 24
Genetic Databases and Maps......Page 25
Organisms for Genetics Research......Page 27
Summary......Page 30
The Search for the Genetic Material......Page 31
Griffith’s Transformation Experiment......Page 32
Avery’s Transformation Experiment......Page 33
Hershey and Chase’s Bacteriophage Experiment......Page 34
RNA as Viral Genetic Material......Page 36
The Composition and Structure of DNA and RNA......Page 37
The DNA Double Helix......Page 39
DNA in the Cell......Page 42
Prokaryotic Chromosomes......Page 43
Eukaryotic Chromosomes......Page 45
Focus on Genomics: Genome Size and Repetitive DNA Content......Page 47
Unique-Sequence and Repetitive-Sequence DNA......Page 50
Summary......Page 52
Analytical Approaches to Solving Genetics Problems......Page 53
Questions and Problems......Page 54
Semiconservative DNA Replication......Page 58
The Meselson–Stahl Experiment......Page 59
DNA Polymerase I......Page 61
Initiation of Replication......Page 62
Semidiscontinuous DNA Replication......Page 65
Rolling Circle Replication......Page 68
Initiation of Replication......Page 70
Replicating the Ends of Chromosomes......Page 72
Assembling Newly Replicated DNA into Nucleosomes......Page 74
Summary......Page 76
Analytical Approaches to Solving Genetics Problems......Page 77
Questions and Problems......Page 78
Garrod’s Hypothesis of Inborn Errors of Metabolism......Page 82
The One-Gene–One-Enzyme Hypothesis......Page 83
Genetically Based Enzyme Deficiencies in Humans......Page 87
Phenylketonuria......Page 88
Tay–Sachs Disease......Page 90
Gene Control of Protein Structure......Page 91
Sickle-Cell Anemia......Page 92
Cystic Fibrosis......Page 93
Genetic Counseling......Page 94
Carrier Detection......Page 95
Fetal Analysis......Page 96
Analytical Approaches to Solving Genetics Problems......Page 97
Questions and Problems......Page 98
Gene Expression—The Central Dogma: An Overview......Page 103
The Transcription Process......Page 104
Initiation of Transcription at Promoters......Page 105
Elongation of an RNA Chain......Page 106
Termination of an RNA Chain......Page 108
Transcription of Protein-Coding Genes by RNA Polymerase II......Page 109
Focus on Genomics: Finding Promoters......Page 110
The Structure and Production of Eukaryotic mRNAs......Page 111
Self-Splicing Introns......Page 117
RNA Editing......Page 118
Summary......Page 119
Questions and Problems......Page 120
Chemical Structure of Proteins......Page 124
Molecular Structure of Proteins......Page 125
The Genetic Code Is a Triplet Code......Page 128
Deciphering the Genetic Code......Page 129
Characteristics of the Genetic Code......Page 130
Transfer RNA......Page 132
Ribosomes......Page 135
Initiation of Translation......Page 137
Elongation of the Polypeptide Chain......Page 139
Termination of Translation......Page 142
Protein Sorting in the Cell......Page 144
Summary......Page 145
Analytical Approaches to Solving Genetics Problems......Page 146
Questions and Problems......Page 147
CHAPTER 7 DNA Mutation, DNA Repair, and Transposable Elements......Page 152
Mutations Defined......Page 153
Spontaneous and Induced Mutations......Page 157
Focus on Genomics: Radiation Resistance in the Archaea–Conan the Bacterium......Page 162
Detecting Mutations......Page 167
Direct Reversal of DNA Damage......Page 168
Excision Repair of DNA Damage......Page 169
Human Genetic Diseases Resulting from DNA Replication and Repair Mutations......Page 171
General Features of Transposable Elements......Page 172
Transposable Elements in Bacteria......Page 173
Transposable Elements in Eukaryotes......Page 175
Summary......Page 183
Analytical Approaches to Solving Genetics Problems......Page 184
Questions and Problems......Page 186
CHAPTER 8 Genomics: The Mapping and Sequencing of Genomes......Page 192
Converting Genomes into Clones, and Clones into Genomes......Page 193
DNA Cloning......Page 194
Cloning Vectors and DNA Cloning......Page 197
Genomic Libraries......Page 201
Chromosome Libraries......Page 204
Dideoxy Sequencing......Page 205
Pyrosequencing......Page 209
Genome Sequencing Using a Whole-Genome Shotgun Approach......Page 211
Assembling and Finishing Genome Sequences......Page 213
Annotation of Variation in Genome Sequences......Page 214
Identification and Annotation of Gene Sequences......Page 215
Focus on Genomics: The Real Old Blue Eyes......Page 217
Genomes of Archaea......Page 221
Genomes of Eukarya......Page 222
Genomes of Archaea......Page 224
Genomes of Eukarya......Page 225
Future Directions in Genomics......Page 227
Ethical, Legal, and Social Implications of the Human Genome......Page 228
Summary......Page 229
Analytical Approaches to Solving Genetics Problems......Page 230
Questions and Problems......Page 233
CHAPTER 9 Functional and Comparative Genomics......Page 239
Sequence Similarity Searches to Assign Gene Function......Page 240
Assigning Gene Function Experimentally......Page 242
Organization of the Genome......Page 251
Describing Patterns of Gene Expression......Page 252
Comparative Genomics......Page 256
Examples of Comparative Genomics Studies and Uses......Page 257
Focus on Genomics: The Neanderthal Genome Project......Page 258
Analytical Approaches to Solving Genetics Problems......Page 263
Questions and Problems......Page 265
CHAPTER 10 Recombinant DNA Technology......Page 270
Expression Vectors......Page 271
PCR Cloning Vectors......Page 274
Transcribable Vectors......Page 275
Finding a Specific Clone Using a DNA Library......Page 277
Focus on Genomics: Finding a New Gene Linked to Type 1 Diabetes......Page 278
Identifying Genes in Libraries by Complementation of Mutations......Page 282
Southern Blot Analysis of Sequences in the Genome......Page 283
Northern Blot Analysis of RNA......Page 284
Applications of PCR......Page 285
RT-PCR and mRNA Qualification......Page 286
Site-Specific Mutagenesis of DNA......Page 287
Analysis of Expression of Individual Genes......Page 288
Analysis of Protein–Protein Interactions......Page 289
Uses of DNA Polymorphisms in Genetic Analysis......Page 291
Classes of DNA Polymorphisms......Page 292
DNA Molecular Testing for Human Genetic Disease Mutations......Page 295
DNA Typing......Page 299
Gene Therapy......Page 302
Biotechnology: Commercial Products......Page 303
Transformation of Plant Cells......Page 304
Applications for Plant Genetic Engineering......Page 306
Summary......Page 308
Analytical Approaches to Solving Genetics Problems......Page 309
Questions and Problems......Page 310
Genotype and Phenotype......Page 319
Mendel’s Experimental Design......Page 320
Monohybrid Crosses and Mendel’s Principle of Segregation......Page 322
The Principle of Segregation......Page 325
Representing Crosses with a Branch Diagram......Page 326
Confirming the Principle of Segregation: The Use of Testcrosses......Page 327
The Wrinkled-Pea Phenotype......Page 328
The Principle of Independent Assortment......Page 329
Branch Diagram of Dihybrid Crosses......Page 331
Trihybrid Crosses......Page 332
Statistical Analysis of Genetic Data: The Chi-Square Test......Page 334
Pedigree Analysis......Page 336
Focus on Genomics: Sometimes Identical Just Isn’t That Similar......Page 337
Examples of Human Genetic Traits......Page 338
Summary......Page 339
Analytical Approaches to Solving Genetics Problems......Page 340
Questions and Problems......Page 341
Chromosomes and Cellular Reproduction......Page 348
Eukaryotic Chromosomes......Page 349
Mitosis......Page 351
Meiosis......Page 355
Focus on Genomics: Genes Involved in Meiotic Chromosome Segregation......Page 359
Sex Chromosomes......Page 361
Sex Linkage......Page 363
Nondisjunction of X Chromosomes......Page 365
Genotypic Sex Determination......Page 368
X-Linked Recessive Inheritance......Page 373
Y-Linked Inheritance......Page 375
Analytical Approaches to Solving Genetics Problems......Page 376
Questions and Problems......Page 378
CHAPTER 13 Extensions of and Deviations from Mendelian Genetic Principles......Page 385
ABO Blood Groups......Page 386
Relating Multiple Alleles to Molecular Genetics......Page 388
Modifications of Dominance Relationships......Page 389
Codominance......Page 390
Essential Genes and Lethal Alleles......Page 391
Gene Expression and the Environment......Page 392
Penetrance and Expressivity......Page 393
Effects of the Environment......Page 394
Nature versus Nurture......Page 397
Maternal Effect......Page 398
Determining the Number of Genes Involved in a Set of Mutations with the Same Phenotype......Page 399
Gene Interactions and Modified Mendelian Ratios......Page 400
Gene Interactions That Produce New Phenotypes......Page 401
Epistasis......Page 402
Focus on Genomics: Redheads of the Past......Page 404
Gene Interactions Involving Modifier Genes......Page 406
Extranuclear Inheritance......Page 407
Examples of Extranuclear Inheritance......Page 408
Summary......Page 411
Analytical Approaches to Solving Genetics Problems......Page 412
Questions and Problems......Page 415
CHAPTER 14 Genetic Mapping in Eukaryotes......Page 423
Early Studies of Genetic Linkage: Morgan’s Experiments with Drosophila......Page 424
Gene Recombination and the Role of Chromosomal Exchange......Page 425
Detecting Linkage through Testcrosses......Page 427
Gene Mapping with Two-Point Testcrosses......Page 429
Generating a Genetic Map......Page 430
Gene Mapping with Three-Point Testcrosses......Page 432
Calculating Accurate Map Distances......Page 437
The lod Score Method for Analyzing Linkage of Human Genes......Page 438
Human Genetic Maps......Page 439
Summary......Page 440
Analytical Approaches to Solving Genetics Problems......Page 441
Questions and Problems......Page 443
CHAPTER 15 Genetics of Bacteria and Bacteriophages......Page 451
Genetics Analysis of Bacteria......Page 452
Discovery of Conjugation in E. coli......Page 453
The Sex Factor F......Page 454
F\' Factors......Page 456
Circularity of the E. coli Map......Page 457
Genetic Mapping in Bacteria by Transformation......Page 459
Focus on Genomics: Artificial Life–Artificial Genomes and Genome Transfer......Page 460
Bacteriophages......Page 462
Transduction Mapping of Bacterial Chromosomes......Page 463
Mapping Bacteriophage Genes......Page 467
Recombination Analysis of rII Mutants......Page 469
Deletion Mapping......Page 471
Defining Genes by Complementation (Cis-Trans) Tests......Page 473
Summary......Page 474
Analytical Approaches to Solving Genetics Problems......Page 475
Questions and Problems......Page 477
Types of Chromosomal Mutations......Page 485
Deletion......Page 486
Duplication......Page 489
Inversion......Page 490
Focus on Genomics: Gene Duplications and Deletions in the Androgen-Binding Protein Family......Page 491
Translocation......Page 492
Chromosomal Mutations and Human Tumors......Page 494
Fragile Sites and Fragile X Syndrome......Page 497
Changes in One or a Few Chromosomes......Page 498
Changes in Complete Sets of Chromosomes......Page 502
Analytical Approaches to Solving Genetics Problems......Page 505
Questions and Problems......Page 507
CHAPTER 17 Regulation of Gene Expression in Bacteria and Bacteriophages......Page 513
Lactose as a Carbon Source for E. coli......Page 514
Experimental Evidence for the Regulation of lac Genes......Page 516
Jacob and Monod’s Operon Model for the Regulation of lac Genes......Page 517
Positive Control of the lac Operon......Page 521
Molecular Details of lac Operon Regulation......Page 524
The trp Operon of E. coli......Page 525
Regulation of the trp Operon......Page 526
The ara Operon of E. coli: Positive and Negative Control......Page 529
Early Transcription Events......Page 531
The Lysogenic Pathway......Page 532
The Lytic Pathway......Page 533
Summary......Page 534
Analytical Approaches to Solving Genetics Problems......Page 535
Questions and Problems......Page 536
CHAPTER 18 Regulation of Gene Expression in Eukaryotes......Page 540
Control of Transcription Initiation by Regulatory Proteins......Page 541
Regulation of Transcription Initiation by Activators......Page 542
Inhibiting Transcription Initiation by Repressors......Page 543
Case Study: Positive and Negative Regulation of Transcription of the Yeast Galactose Utilization Genes......Page 544
Case Study: Regulation of Transcription in Animals by Steroid Hormones......Page 545
Combinatorial Gene Regulation: The Control of Transcription by Combinations of Activators and Repressors......Page 548
Facilitation of Transcription Activation by Remodeling of Chromatin......Page 551
Gene Silencing by DNA Methylation......Page 553
Focus on Genomics: ChIP on Chip......Page 554
Genomic Imprinting......Page 555
RNA Processing Control: Alternative Polyadenylation and Alternative Splicing......Page 556
mRNA Translation Control by Ribosome Selection......Page 558
The Roles of Small Regulatory RNAs in Posttranscriptional Gene Silencing......Page 559
Control of mRNA Degradation......Page 562
Summary......Page 563
Analytical Approaches to Solving Genetics Problems......Page 564
Questions and Problems......Page 565
Basic Events of Development......Page 569
Model Organisms for the Genetic Analysis of Development......Page 570
Constancy of DNA in the Genome during Development......Page 572
Examples of Differential Gene Activity during Development......Page 574
Exception to the Constancy of Genomic DNA during Development: DNA Loss in Antibody-Producing Cells......Page 575
Sex Determination in Mammals......Page 579
Dosage Compensation Mechanism for X-Linked Genes in Mammals......Page 580
Sex Determination in Drosophila......Page 581
Dosage Compensation in Drosophila......Page 584
Embryonic Development......Page 586
Microarray Analysis of Drosophila Development......Page 593
Summary......Page 594
Analytical Approaches to Solving Genetics Problems......Page 595
Questions and Problems......Page 596
CHAPTER 20 Genetics of Cancer......Page 600
Molecular Control of the Cell Cycle......Page 601
Regulation of Cell Division in Normal Cells......Page 602
Cancers Are Genetic Diseases......Page 603
Oncogenes......Page 604
Tumor Suppressor Genes......Page 610
MicroRNA Genes......Page 615
Mutator Genes......Page 616
The Multistep Nature of Cancer......Page 617
Chemical Carcinogens......Page 618
Radiation......Page 619
Summary......Page 620
Questions and Problems......Page 621
CHAPTER 21 Population Genetics......Page 625
Allele Frequencies......Page 627
The Hardy–Weinberg Law......Page 630
Derivation of the Hardy–Weinberg Law......Page 631
Extensions of the Hardy–Weinberg Law to Loci with More than Two Alleles......Page 633
Testing for Hardy–Weinberg Proportions......Page 634
Using the Hardy–Weinberg Law to Estimate Allele Frequencies......Page 635
Genetic Variation in Natural Populations......Page 636
Measuring Genetic Variation at the Protein Level......Page 637
Measuring Genetic Variation at the DNA Level......Page 640
Forces That Change Gene Frequencies in Populations......Page 643
Mutation......Page 644
Random Genetic Drift......Page 646
Migration......Page 651
Natural Selection......Page 652
Assortative Mating......Page 660
Inbreeding......Page 661
The Effects of Crossing Over on Genetic Variation......Page 662
Speciation......Page 663
Genetic Basis for Speciation......Page 664
Analytical Approaches to Solving Genetics Problems......Page 665
Questions and Problems......Page 666
The Nature of Continuous Traits......Page 672
The Inheritance of Continuous Traits......Page 673
Polygene Hypothesis for Wheat Kernel Color......Page 674
Statistical Tools......Page 675
The Mean......Page 676
The Variance and the Standard Deviation......Page 677
Correlation......Page 678
Regression......Page 680
Analysis of Variance......Page 681
Inheritance of Ear Length in Corn......Page 682
Components of the Phenotypic Variance......Page 683
Broad-Sense and Narrow-Sense Heritability......Page 685
Understanding Heritability......Page 686
How Heritability is Calculated......Page 687
Response to Selection......Page 688
Estimating the Response to Selection......Page 689
Genetic Correlations......Page 690
Quantitative Trait Loci......Page 692
Focus on Genomics: QTL Analysis of Aggression in Drosophila melanogaster......Page 695
Summary......Page 696
Analytical Approaches to Solving Genetics Problems......Page 697
Questions and Problems......Page 698
CHAPTER 23 Molecular Evolution......Page 705
Nucleotide Substitutions in DNA Sequences......Page 706
Rates of Nucleotide Substitutions......Page 707
Variation in Evolutionary Rates between Genes......Page 710
Molecular Clocks......Page 712
Phylogenetic Trees......Page 714
Focus on Genomics: Horizontal Gene Transfer......Page 716
Reconstruction Methods......Page 717
Phylogenetic Trees on a Grand Scale......Page 720
Multigene Families......Page 722
Arabidopsis Genome......Page 723
Summary......Page 724
Questions and Problems......Page 725
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Suggested Readings......Page 750
Solutions to Selected Questions and Problems......Page 764
Credits......Page 824
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