Concepts of genetics.

Cover......Page 1
Title Page......Page 2
Copyright Page......Page 3
Dedication......Page 4
About the Authors......Page 5
Brief Contents......Page 6
Explore Cutting Edge Topics......Page 7
Explore Classic and Modern Approaches......Page 8
Learn and Practice Problem Solving......Page 9
Succeed with MasteringGenetics......Page 11
Contents......Page 12
Preface......Page 29
1. Introduction to Genetics......Page 36
  1600–1850: The Dawn of Modern Biology......Page 37
  Mendel’s Work on Transmission of Traits......Page 38
  Genetic Variation......Page 39
 1.3. Discovery of the Double Helix Launched the Era of Molecular Genetics......Page 40
  Gene Expression: From DNA to Phenotype......Page 41
  Linking Genotype to Phenotype: Sickle-Cell Anemia......Page 42
  Plants, Animals, and the Food Supply......Page 43
 1.6. Genomics, Proteomics, and Bioinformatics are New and Expanding Fields......Page 44
 1.7. Genetic Studies Rely on the Use of Model Organisms......Page 45
  Model Organisms and Human Diseases......Page 46
  Genetics and Society......Page 47
 Internet Resources for Learning About Genomics, Bioinformatics, and Proteomics......Page 48
 Summary Points......Page 49
 Problems and Discussion Questions......Page 50
2. Mitosis and Meiosis......Page 51
 2.1. Cell Structure Is Closely Tied to Genetic Function......Page 52
 2.2. Chromosomes Exist in Homologous Pairs in Diploid Organisms......Page 54
  Interphase and the Cell Cycle......Page 56
  Prophase......Page 57
  Anaphase......Page 59
  Cell-Cycle Regulation and Checkpoints......Page 60
  An Overview of Meiosis......Page 61
  The First Meiotic Division: Prophase I......Page 63
  The Second Meiotic Division......Page 64
 2.5. The Development of Gametes Varies in Spermatogenesis Compared to Oogenesis......Page 66
 2.7. Electron Microscopy Has Revealed the Physical Structure of Mitotic and Meiotic Chromosomes......Page 68
 Summary Points......Page 70
 Insights and Solutions......Page 71
 Problems and Discussion Questions......Page 72
3. Mendelian Genetics......Page 75
 3.1. Mendel Used a Model Experimental Approach to Study Patterns of Inheritance......Page 76
  Mendel’s First Three Postulates......Page 77
  Mendel’s Analytical Approach......Page 78
  Punnett Squares......Page 79
  The Testcross: One Character......Page 80
  Mendel’s Fourth Postulate: Independent Assortment......Page 81
  The Testcross: Two Characters......Page 82
 3.4. The Trihybrid Cross Demonstrates That Mendel’s Principles Apply to Inheritance of Multiple Traits......Page 84
  The Forked-Line Method, or Branch Diagram......Page 85
 3.5. Mendel’s Work was Rediscovered in the Early Twentieth Century......Page 86
  Unit Factors, Genes, and Homologous Chromosomes......Page 87
 3.7. Laws of Probability Help to Explain Genetic Events......Page 89
  The Binomial Theorem......Page 90
  Chi-Square Calculations and the Null Hypothesis......Page 91
  Interpreting Probability Values......Page 92
  Pedigree Conventions......Page 94
  Pedigree Analysis......Page 95
  How Mendel’s Peas Become Wrinkled: A Molecular Explanation......Page 96
 Online Mendelian Inheritance in Man......Page 97
 Summary Points......Page 98
 Insights and Solutions......Page 99
 Problems and Discussion Questions......Page 101
4. Extensions of Mendelian Genetics......Page 105
 4.1. Alleles Alter Phenotypes in Different Ways......Page 106
 4.3. Neither Allele is Dominant in Incomplete, or Partial, Dominance......Page 107
 4.4. In Codominance, the Influence of Both Alleles in a Heterozygote Is Clearly Evident......Page 108
  The A and B Antigens......Page 109
  The Bombay Phenotype......Page 110
 4.6. Lethal Alleles Represent Essential Genes......Page 111
  The Molecular Basis of Dominance, Recessiveness, and Lethality: The Agouti Gene......Page 112
 4.7. Combinations of Two Gene Pairs with Two Modes of Inheritance Modify the 9:3:3:1 Ratio......Page 113
 4.8. Phenotypes are Often Affected by More Than One Gene......Page 114
  Epistasis......Page 115
  Novel Phenotypes......Page 118
 4.9. Complementation Analysis Can Determine if Two Mutations Causing a Similar Phenotype are Alleles of the Same Gene......Page 120
 4.10. Expression of a Single Gene May Have Multiple Effects......Page 121
  X-Linkage in Drosophila......Page 122
  X-Linkage in Humans......Page 123
 4.12. In Sex-Limited and Sex-Influenced Inheritance, an Individual’s Sex Influences the Phenotype......Page 124
 4.13. Genetic Background and the Environment May Alter Phenotypic Expression......Page 125
  Temperature Effects—An Introduction to Conditional Mutations......Page 126
  Nutritional Effects......Page 127
  Genomic (Parental) Imprinting and Gene Silencing......Page 128
 Improving the Genetic Fate of Purebred Dogs......Page 129
 Case Study: But he isn’t Deaf......Page 130
 Insights and Solutions......Page 131
 Problems and Discussion Questions......Page 133
5. Chromosome Mapping in Eukaryotes......Page 139
 5.1. Genes Linked on the Same Chromosome Segregate Together......Page 140
  The Linkage Ratio......Page 141
  Sturtevant and Mapping......Page 143
  Single Crossovers......Page 145
  Multiple Exchanges......Page 146
  Three-Point Mapping in Drosophila......Page 147
  Determining the Gene Sequence......Page 149
  A Mapping Problem in Maize......Page 151
  Interference and the Coefficient of Coincidence......Page 154
 5.5. Drosophila Genes Have Been Extensively Mapped......Page 155
 5.6. Lod Score Analysis and Somatic Cell Hybridization Were Historically Important in Creating Human Chromosome Maps......Page 156
 5.7. Chromosome Mapping is Now Possible Using DNA Markers and Annotated Computer Databases......Page 158
 5.8. Crossing Over Involves a Physical Exchange Between Chromatids......Page 159
 5.9. Exchanges Also Occur between Sister Chromatids during Mitosis......Page 160
 5.10. Did Mendel Encounter Linkage?......Page 161
 Case Study: Links to Autism......Page 162
 Insights and Solutions......Page 163
 Problems and Discussion Questions......Page 165
6. Genetic Analysis and Mapping in Bacteria and Bacteriophages......Page 169
 6.1. Bacteria Mutate Spontaneously and Grow at an Exponential Rate......Page 170
  Conjugation in Bacteria: The Discovery of F+ and F- Strains......Page 171
  Hfr Bacteria and Chromosome Mapping......Page 173
  The F' State and Merozygotes......Page 176
 6.3. Rec Proteins are Essential to Bacterial Recombination......Page 178
 6.4. The F Factor Is an Example of a Plasmid......Page 179
  The Transformation Process......Page 180
 6.6. Bacteriophages are Bacterial Viruses......Page 181
  The Plaque Assay......Page 182
  The Lederberg–Zinder Experiment......Page 184
  The Nature of Transduction......Page 185
  Bacteriophage Mutations......Page 186
  Mapping in Bacteriophages......Page 187
  The rll Locus of Phage T4......Page 188
  Recombinational Analysis......Page 189
  Deletion Testing of the rll Locus......Page 190
  The rll Gene Map......Page 191
 From Cholera Genes to Edible Vaccines......Page 193
 Insights and Solutions......Page 194
 Problems and Discussion Questions......Page 196
7. Sex Determination and Sex Chromosomes......Page 199
  Zea Mays......Page 200
  Caenorhabditis Elegans......Page 202
 7.2. X and Y Chromosomes Were First Linked to Sex Determination Early in the Twentieth Century......Page 203
 7.3. The Y Chromosome Determines Maleness in Humans......Page 204
  Klinefelter and Turner Syndromes......Page 205
  47,XYY Condition......Page 206
  The Y Chromosome and Male Development......Page 207
 7.4. The Ratio of Males to Females in Humans Is Not 1.0......Page 209
  Barr Bodies......Page 210
  The Lyon Hypothesis......Page 211
  The Mechanism of Inactivation......Page 212
 7.6. The Ratio of X Chromosomes to Sets of Autosomes Determines Sex in Drosophila......Page 214
  Dosage Compensation in Drosophila......Page 215
 7.7. Temperature Variation Controls Sex Determination in Reptiles......Page 217
 Drosophila Sxl Gene Induces Female Development......Page 216
 A Question of Gender: Sex Selection in Humans......Page 219
 Insights and Solutions......Page 220
 Problems and Discussion Questions......Page 221
8. Chromosome Mutations: Variation in Number and Arrangement......Page 223
  Monosomy......Page 224
  Trisomy......Page 225
  Down Syndrome: Trisomy 21......Page 226
 Mouse Models of Down Syndrome......Page 227
  The Origin of the Extra 21st Chromosome in Down Syndrome......Page 228
 8.3. Polyploidy, in Which More Than Two Haploid Sets of Chromosomes Are Present, Is Prevalent in Plants......Page 230
  Autopolyploidy......Page 231
  Allopolyploidy......Page 232
  Endopolyploidy......Page 233
 8.4. Variation Occurs in the Composition and Arrangement of Chromosomes......Page 234
  Cri du Chat Syndrome in Humans......Page 235
  Gene Redundancy and Amplification—Ribosomal RNA Genes......Page 236
  The Role of Gene Duplication in Evolution......Page 237
 8.7. Inversions Rearrange the Linear Gene Sequence......Page 238
  Consequences of Inversions during Gamete Formation......Page 239
 8.8. Translocations Alter the Location of Chromosomal Segments in the Genome......Page 240
  Translocations in Humans: Familial Down Syndrome......Page 241
  Fragile-X Syndrome......Page 242
  The Link Between Fragile Sites and Cancer......Page 243
 Down Syndrome and Prenatal Testing—The New Eugenics?......Page 244
 Insights and Solutions......Page 245
 Problems and Discussion Questions......Page 246
9. Extranuclear Inheritance......Page 249
  Chloroplast Mutations in Chlamydomonas......Page 250
  Mitochondrial Mutations: Early Studies in Neurospora and Yeast......Page 251
  Organelle DNA and the Endosymbiotic Theory......Page 253
  Molecular Organization and Gene Products of Chloroplast DNA......Page 254
  Molecular Organization and Gene Products of Mitochondrial DNA......Page 255
 9.3. Mutations in Mitochondrial DNA Cause Human Disorders......Page 256
  Mitochondria, Human Health, and Aging......Page 257
  Future Prevention of the Transmission of mtDNA-Based Disorders......Page 258
  Lymnaea Coiling......Page 259
  Embryonic Development in Drosophila......Page 260
 Mitochondrial DNA and the Mystery of the Romanovs......Page 261
 Case Study: A Twin Difference......Page 262
 Problems and Discussion Questions......Page 263
10. DNA Structure and Analysis......Page 266
 10.2. Until 1944, Observations Favored Protein as the Genetic Material......Page 267
  Transformation: Early Studies......Page 268
  Transformation: The Avery, MacLeod, and McCarty Experiment......Page 269
  The Hershey–Chase Experiment......Page 271
  Transfection Experiments......Page 272
  Direct Evidence: Recombinant DNA Studies......Page 274
  Nucleotides: Building Blocks of Nucleic Acids......Page 275
  Polynucleotides......Page 277
 10.7. The Structure of DNA Holds the Key to Understanding Its Function......Page 278
  Base-Composition Studies......Page 279
  The Watson–Crick Model......Page 280
 10.8. Alternative Forms of DNA Exist......Page 284
 10.9. The Structure of RNA is Chemically Similar to DNA , but Single Stranded......Page 285
  Denaturation and Renaturation of Nucleic Acids......Page 286
  Fluorescent in situ Hybridization (FISH)......Page 287
  Reassociation Kinetics and Repetitive DNA......Page 288
  Electrophoresis of Nucleic Acids......Page 289
 Introduction to Bioinformatics: BLAST......Page 290
 Summary Points......Page 291
 Insights and Solutions......Page 292
 Problems and Discussion Questions......Page 293
11. DNA Replication and Recombination......Page 296
 11.1. DNA Is Reproduced by Semiconservative Replication......Page 297
  The Meselson–Stahl Experiment......Page 298
  Semiconservative Replication in Eukaryotes......Page 299
  Origins, Forks, and Units of Replication......Page 300
  DNA Polymerase I......Page 301
  DNA Polymerase II, III, IV, and V......Page 302
  The DNA Pol III Holoenzyme......Page 303
  Unwinding the DNA Helix......Page 304
  Continuous and Discontinuous DNA Synthesis......Page 305
  Concurrent Synthesis Occurs on the Leading and Lagging Strands......Page 306
 11.4. A Coherent Model Summarizes DNA Replication......Page 307
 Lethal Knockouts of DNA Ligase Genes......Page 308
  Initiation at Multiple Replication Origins......Page 310
  Replication through Chromatin......Page 311
  Replication at the Telomere......Page 312
  Models of Homologous Recombination......Page 314
  Gene Conversion, a Consequence of Homologous Recombination......Page 316
 Telomeres: The Key to Immortality?......Page 318
 Insights and Solutions......Page 319
 Problems and Discussion Questions......Page 320
12. DNA Organization in Chromosomes......Page 323
 12.1. Viral and Bacterial Chromosomes Are Relatively Simple DNA Molecules......Page 324
 12.2. Supercoiling Facilitates Compaction of the DNA of Viral and Bacterial Chromosomes......Page 325
  Polytene Chromosomes......Page 327
  Lampbrush Chromosomes......Page 328
  Chromatin Structure and Nucleosomes......Page 329
  Chromatin Remodeling......Page 331
 12.5. Chromosome Banding Differentiates Regions along the Mitotic Chromosome......Page 333
 12.6. Eukaryotic Genomes Demonstrate Complex Sequence Organization Characterized by Repetitive DNA......Page 334
  Satellite DNA......Page 335
  Middle Repetitive Sequences: VNTRs and STRs......Page 336
 12.7. The Vast Majority of a Eukaryotic Genome Does Not Encode Functional Genes......Page 337
 Database of Genomic Variants: Structural Variations in the Human Genome......Page 338
 Insights and Solutions......Page 339
 Problems and Discussion Questions......Page 340
13. The Genetic Code and Transcription......Page 343
 13.2. Early Studies Established the Basic Operational Patterns of the Code......Page 344
  The Nonoverlapping Nature of the Code......Page 345
  Synthesizing Polypeptides in a Cell-Free System......Page 346
  Mixed Copolymers......Page 347
  The Triplet-Binding Assay......Page 348
  Repeating Copolymers......Page 350
  Degeneracy and the Wobble Hypothesis......Page 351
  Initiation, Termination, and Suppression......Page 352
 13.6. The Genetic Code Is Nearly Universal......Page 353
 13.7. Different Initiation Points Create Overlapping Genes......Page 354
 13.9. Studies with Bacteria and Phages Provided Evidence for the Existence of mRNA......Page 355
 13.10. RNA Polymerase Directs RNA Synthesis......Page 356
  Promoters, Template Binding, and the S Subunit......Page 357
 13.11. Transcription in Eukaryotes Differs from Prokaryotic Transcription in Several Ways......Page 358
  Initiation of Transcription in Eukaryotes......Page 359
  Recent Discoveries Concerning RNA Polymerase Function......Page 360
 13.12. The Coding Regions of Eukaryotic Genes Are Interrupted by Intervening Sequences Called Introns......Page 361
  Splicing Mechanisms: The Spliceosome......Page 363
 13.14. Transcription Has Been Visualized by Electron Microscopy......Page 365
 Summary Points......Page 366
 Fighting Disease with Antisense Therapeutics......Page 367
 Problems and Discussion Questions......Page 368
 14.1. Translation of mRNA Depends on Ribosomes and Transfer RNAs......Page 372
  Ribosomal Structure......Page 373
  tRNA Structure......Page 374
  Charging tRNA......Page 375
 14.2. Translation of mRNA Can Be Divided into Three Steps......Page 376
  Elongation......Page 377
  Polyribosomes......Page 379
 14.3. High-Resolution Studies Have Revealed Many Details about the Functional Prokaryotic Ribosome......Page 380
 14.4. Translation Is More Complex in Eukaryotes......Page 381
 14.5. The Initial Insight That Proteins Are Important in Heredity Was Provided by the Study of Inborn Errors of Metabolism......Page 382
  Analysis of Neurospora Mutants by Beadle and Tatum......Page 383
  Genes and Enzymes: Analysis of Biochemical Pathways......Page 385
  Sickle-Cell Anemia......Page 386
 14.8. The Nucleotide Sequence of a Gene and the Amino Acid Sequence of the Corresponding Protein Exhibit Colinearity......Page 388
 14.9. Variation in Protein Structure Provides the Basis of Biological Diversity......Page 389
 14.10. Posttranslational Modification Alters the Final Protein Product......Page 392
  Protein Folding and Misfolding......Page 393
 14.11. Proteins Function in Many Diverse Roles......Page 394
  Exon Shuffling......Page 395
 Translation Tools and Swiss-Prot for Studying Protein Sequences......Page 396
 Case Study: Crippled Ribosomes......Page 397
 Problems and Discussion Questions......Page 398
15. Gene Mutation, DNA Repair, and Transposition......Page 402
  Classification Based on Type of Molecular Change......Page 403
  Classification Based on Phenotypic Effects......Page 404
  Spontaneous and Induced Mutations......Page 405
  The Fluctuation Test: Are Mutations Random or Adaptive?......Page 406
  Tautomeric Shifts......Page 408
  Oxidative Damage......Page 409
  Alkylating, Intercalating, and Adduct-Forming Agents......Page 410
  Ultraviolet Light......Page 411
  Ionizing Radiation......Page 412
 15.5. Single-Gene Mutations Cause a Wide Range of Human Diseases......Page 413
  Mutations Caused by Expandable DNA Repeats......Page 414
  Proofreading and Mismatch Repair......Page 415
  Base and Nucleotide Excision Repair......Page 416
  Nucleotide Excision Repair and Xeroderma Pigmentosum in Humans......Page 418
  Double-Strand Break Repair in Eukaryotes......Page 419
 15.7. The Ames Test Is Used to Assess the Mutagenicity of Compounds......Page 420
  Insertion Sequences and Bacterial Transposons......Page 421
  The Ac–Ds System in Maize......Page 422
  Transposable Elements in Humans......Page 423
 Transposon-Mediated Mutations Reveal Genes Involved in Colorectal Cancer......Page 424
 Transposons, Mutations, and Evolution......Page 425
 Case Study: Genetic Dwarfism......Page 426
 Insights and Solutions......Page 427
 Problems and Discussion Questions......Page 428
16. Regulation of Gene Expression in Prokaryotes......Page 431
 16.2. Lactose Metabolism in E. coli Is Regulated by an Inducible System......Page 432
  Structural Genes......Page 433
  Genetic Proof of the Operon Model......Page 434
  Isolation of the Repressor......Page 436
 16.3. The Catabolite-Activating Protein (CAP) Exerts Positive Control over the lac Operon......Page 437
 16.4. Crystal Structure Analysis of Repressor Complexes Has Confirmed the Operon Model......Page 439
  Evidence for the trp Operon......Page 441
 16.6. Alterations to RNA Secondary Structure Contribute to Prokaryotic Gene Regulation......Page 442
  Attenuation......Page 443
  Riboswitches......Page 444
 16.7. The ara Operon Is Controlled by a Regulator Protein That Exerts Both Positive and Negative Control......Page 445
 Summary Points......Page 446
 Quorum Sensing: Social Networking in the Bacterial World......Page 447
 Problems and Discussion Questions......Page 448
17. Regulation of Gene Expression in Eukaryotes......Page 452
 17.1. Eukaryotic Gene Regulation Can Occur at Any of the Steps Leading from DNA to Protein Product......Page 453
  Open and Closed Chromatin......Page 454
  DNA Methylation......Page 455
  Promoter Elements......Page 456
  Enhancers and Silencers......Page 457
  The Human Metallothionein IIA Gene: Multiple Cis-Acting Elements and Transcription Factors......Page 459
  Formation of the RNA Polymerase II Transcription Initiation Complex......Page 460
  Mechanisms of Transcription Activation and Repression......Page 461
 17.6. Gene Regulation in a Model Organism: Transcription of the GAL Genes of Yeast......Page 462
 17.7. Posttranscriptional Gene Regulation Occurs at Many Steps from RNA Processing to Protein Modification......Page 463
  Alternative Splicing of mRNA......Page 464
  Sex Determination in Drosophila: A Model for Regulation of Alternative Splicing......Page 465
 17.8. RNA Silencing Controls Gene Expression in Several Ways......Page 467
  The Molecular Mechanisms of RNA-Induced Gene Silencing......Page 468
  RNA-Induced Gene Silencing in Biotechnology and Medicine......Page 469
 MicrorRNAs Regulate Ovulation in Female Mice......Page 470
  The Immune System and Antibody Diversity......Page 471
  Gene Rearrangements in the K Light-Chain Gene......Page 472
  Enhancer and Promoter Elements......Page 473
  Tissue-Specific Gene Expression......Page 474
 Summary Points......Page 475
 Insights and Solutions......Page 476
 Problems and Discussion Questions......Page 477
 18.1. Differentiated States Develop from Coordinated Programs of Gene Expression......Page 480
 18.2. Evolutionary Conservation of Developmental Mechanisms Can Be Studied Using Model Organisms......Page 481
  Overview of Drosophila Development......Page 482
  Genetic Analysis of Embryogenesis......Page 483
  Segment Polarity Genes......Page 485
  Segmentation Genes in Mice and Humans......Page 486
 Problems and Discussion Questions......Page 487
  Hox Genes and Human Genetic Disorders......Page 489
  Homeotic Genes in Arabidopsis......Page 490
  Evolutionary Divergence in Homeotic Genes......Page 491
  Signaling Pathways in Development......Page 492
 Single-Gene Signaling Mechanism Reveals Secrets to Head Regeneration in Planaria......Page 493
  Overview of C. elegans Development......Page 494
  Genetic Analysis of Vulva Formation......Page 495
  The Control of Eye Formation......Page 497
 Stem Cell Wars......Page 499
 Summary Points......Page 500
 Problems and Discussion Questions......Page 501
19. Cancer and Regulation of the Cell Cycle......Page 504
  The Clonal Origin of Cancer Cells......Page 505
  Cancer as a Multistep Process, Requiring Multiple Mutations......Page 506
 19.2. Cancer Cells Contain Genetic Defects Affecting Genomic Stability, DNA Repair, and Chromatin Modifications......Page 507
  Genomic Instability and Defective DNA Repair......Page 508
  The Cell Cycle and Signal Transduction......Page 509
  Cell-Cycle Control and Checkpoints......Page 510
 19.4. Proto-Oncogenes and Tumor-Suppressor Genes are Altered in Cancer Cells......Page 511
  The p53 Tumor-Suppressor Gene......Page 513
  The RB1 Tumor-Suppressor Gene......Page 514
 19.5. Cancer Cells Metastasize and Invade Other Tissues......Page 516
 19.7. Viruses Contribute to Cancer in Both Humans and Animals......Page 517
 19.8. Environmental Agents Contribute to Human Cancers......Page 519
 Summary Points......Page 520
 Insights and Solutions......Page 521
20. Recombinant DNA Technology......Page 524
  Restriction Enzymes Cut DNA at Specific Recognition Sequences......Page 525
  DNA Vectors Accept and Replicate DNA Molecules to Be Cloned......Page 526
  Bacterial Plasmid Vectors......Page 527
  Other Types of Cloning Vectors......Page 529
  Host Cells for Cloning Vectors......Page 530
  Complementary DNA (cDNA) Libraries......Page 531
  Specific Genes Can Be Recovered from a Library by Screening......Page 532
 20.3. The Polymerase Chain Reaction Is a Powerful Technique for Copying DNA......Page 533
  Limitations of PCR......Page 536
  Applications of PCR......Page 537
  Restriction Mapping......Page 538
  Nucleic Acid Blotting......Page 539
 20.5. DNA Sequencing Is the Ultimate Way to Characterize DNA Structure at the Molecular Level......Page 542
  Next-Generation and Third-Generation Sequencing Technologies......Page 544
  Gene Targeting and Knockout Animal Models......Page 546
  Making a Transgenic Animal: The Basics......Page 550
 Manipulating Recombinant DNA : Restriction Mapping and Designing PCR Primers......Page 551
 Summary Points......Page 552
 Problems and Discussion Questions......Page 553
21. Genomics, Bioinformatics, and Proteomics......Page 557
 21.1. Whole-Genome Sequencing Is a Widely Used Method for Sequencing and Assembling Entire Genomes......Page 558
  High-Throughput Sequencing and Its Impact on Genomics......Page 559
  The Clone-By-Clone Approach......Page 560
 21.2. DNA Sequence Analysis Relies on Bioinformatics Applications and Genome Databases......Page 562
  Annotation to Identify Gene Sequences......Page 563
  Hallmark Characteristics of a Gene Sequence Can Be Recognized During Annotation......Page 564
  Predicting Gene and Protein Functions by Sequence Analysis......Page 566
  Investigators Are Using Genomics Techniques Such as Chromatin Immunoprecipitation to Investigate Aspects of Genome Function and Regulation......Page 567
 21.4. The Human Genome Project Revealed Many Important Aspects of Genome Organization in Humans......Page 568
  Major Features of the Human Genome......Page 569
  Individual Variations in the Human Genome......Page 570
  Accessing the Human Genome Project on the Internet......Page 571
  Stone-Age Genomics......Page 573
  Personal Genome Projects and Personal Genomics......Page 574
  Encyclopedia of DNA Elements (ENCODE) Project......Page 576
  The Human Microbiome Project......Page 577
  No Genome Left Behind and the Genome 10K Plan......Page 578
  Prokaryotic and Eukaryotic Genomes Display Common Structural and Functional Features and Important Differences......Page 579
  The Sea Urchin Genome......Page 581
  The Chimpanzee Genome......Page 582
  The Neanderthal Genome and Modern Humans......Page 583
 21.7. Comparative Genomics Is Useful for Studying the Evolution and Function of Multigene Families......Page 584
 21.8. Metagenomics Applies Genomics Techniques to Environmental Samples......Page 586
  Microarray Analysis......Page 588
  Reconciling the Number of Genes and the Number of Proteins Expressed by a Cell or Tissue......Page 591
  Proteomics Technologies: Two-Dimensional Gel Electrophoresis for Separating Proteins......Page 592
  Proteomics Technologies: Mass Spectrometry for Protein Identification......Page 593
  Identification of Collagen in Tyrannosaurus rex and Mammut americanum Fossils......Page 596
 21.11. Systems Biology Is an Integrated Approach to Studying Interactions of All Components of an Organism’s Cells......Page 597
 Contigs, Shotgun Sequencing, and Comparative Genomics......Page 599
 Summary Points......Page 600
 Problems and Discussion Questions......Page 601
22. Applications and Ethics of Genetic Engineering and Biotechnology......Page 604
  Insulin Production in Bacteria......Page 605
  Transgenic Animal Hosts and Pharmaceutical Products......Page 606
  DNA-Based Vaccines......Page 608
 22.2. Genetic Engineering of Plants Has Revolutionized Agriculture......Page 609
  Examples of Transgenic Animals......Page 610
  How Simple Can a Genome Be?......Page 611
  Transplantation of a Synthetic Genome......Page 612
  Synthetic Biology for Bioengineering Applications......Page 614
  Prenatal Genetic Testing......Page 615
  Genetic Tests Based on Restriction Enzyme Analysis......Page 617
  Genetic Testing Using Allele-Specific Oligonucleotides......Page 618
  Genetic Testing Using DNA Microarrays and Genome Scans......Page 620
  Genetic Analysis Using Gene-Expression Microarrays......Page 622
  Application of Microarrays for Gene Expression and Genotype Analysis of Pathogens......Page 624
 22.6. Genetic Analysis by Individual Genome Sequencing......Page 626
 22.7. Genome-Wide Association Studies Identify Genome Variations That Contribute to Disease......Page 627
  Pharmacogenomics and Rational Drug Design......Page 628
  Genetic Testing and Ethical Dilemmas......Page 630
  Direct-To-Consumer Genetic Testing and Regulating the Genetic Test Providers......Page 631
  DNA and Gene Patents......Page 632
  Patents and Synthetic Biology......Page 633
 Privacy and Anonymity in the Era of Genomic Big Data......Page 634
 Insights and Solutions......Page 635
 Problems and Discussion Questions......Page 636
23. Quantitative Genetics and Multifactorial Traits......Page 639
  The Multiple-Gene Hypothesis for Quantitative Inheritance......Page 640
  Additive Alleles: The Basis of Continuous Variation......Page 641
  Calculating the Number of Polygenes......Page 642
  The Mean......Page 643
  Covariance and Correlation Coefficient......Page 644
  Analysis of a Quantitative Character......Page 645
 23.4. Heritability Values Estimate the Genetic Contribution to Phenotypic Variability......Page 646
  Narrow-Sense Heritability......Page 647
  Artificial Selection......Page 648
 23.5. Twin Studies Allow an Estimation of Heritability in Humans......Page 649
  Twin Studies Have Several Limitations......Page 650
 23.6. Quantitative Trait Loci are Useful in Studying Multifactorial Phenotypes......Page 651
  Expression QTLs (eQTLs) and Genetic Disorders......Page 653
 The Green Revolution Revisited: Genetic Research with Rice......Page 654
 Insights and Solutions......Page 655
 Problems and Discussion Questions......Page 656
24. Neurogenetics......Page 660
  Organization of Cells in the Central Nervous System......Page 661
  Synapses Transfer Information Between Neurons......Page 662
 24.2. Identification of Genes Involved in Transmission of Nerve Impulses......Page 663
  A Defect in Neurotransmitter Breakdown......Page 665
  Fragile-X Syndrome and Synapses......Page 666
  Huntington Disease is a Neurodegenerative Behavioral Disorder......Page 667
  Mechanism of Huntington Disease......Page 668
  Treatment Strategies for Huntington Disease......Page 669
  Dissecting the Mechanisms and Neural Pathways in Learning......Page 670
 24.5. Behavioral Disorders Have Environmental Components......Page 671
  RbAp48 and a Potential Molecular Mechanism for Age-Related Memory Loss......Page 672
  Schizophrenia Is a Complex Behavioral Disorder......Page 673
  Several Behavioral Disorders Share a Genetic Relationship......Page 674
  Epigenetics and Mental Illness......Page 675
  Addiction and Alcoholism Are Behaviors with Genetic and Environmental Causes......Page 676
 Homologene: Searching for Behavioral Genes......Page 678
 Problems and Discussion Questions......Page 679
25. Population and Evolutionary Genetics......Page 682
  Variations in Nucleotide Sequence......Page 683
  Explaining the High Level of Genetic Variation in Populations......Page 684
 25.2. The Hardy–Weinberg Law Describes Allele Frequencies and Genotype Frequencies in Populations......Page 685
 25.3. The Hardy–Weinberg Law Can Be Applied to Human Populations......Page 687
  Testing for Hardy–Weinberg Equilibrium in a Population......Page 688
  Calculating Frequencies for Multiple Alleles in Populations......Page 689
 25.4. Natural Selection Is a Major Force Driving Allele Frequency Change......Page 690
  Fitness and Selection......Page 691
  There are Several Types of Selection......Page 692
 25.5. Mutation Creates New Alleles in a Gene Pool......Page 693
 25.6. Migration and Gene Flow Can Alter Allele Frequencies......Page 694
  Founder Effects in Human Populations......Page 695
 25.8. Nonrandom Mating Changes Genotype Frequency but Not Allele Frequency......Page 696
 25.9. Reduced Gene Flow, Selection, and Genetic Drift Can Lead to Speciation......Page 697
  The Rate of Macroevolution and Speciation......Page 698
 25.10. Phylogeny Can Be Used to Analyze Evolutionary History......Page 699
  The Complex Origins of Our Genome......Page 700
 Tracking Our Genetic Footprints out of Africa......Page 703
 Case Study: An Unexpected Outcome......Page 704
 Insights and Solutions......Page 705
 Problems and Discussion Questions......Page 706
Epigenetics......Page 709
  DNA Methylation......Page 710
  MicroRNAs and Long Noncoding RNAs......Page 711
 Epigenetics and Imprinting......Page 712
 Epigenetics and Cancer......Page 714
 Epigenetics and the Environment......Page 716
 Epigenome Projects......Page 717
 Catalytic Activity of RNAs: Ribozymes and the Origin of Life......Page 719
  Genetic Engineering of Ribozymes......Page 721
 Small Noncoding RNAs Play Regulatory Roles in Prokaryotes......Page 722
 Prokaryotes Have an RNA-Guided Viral Defense Mechanism......Page 723
 Small Noncoding RNAs Mediate the Regulation of Eukaryotic Gene Expression......Page 725
  siRNAs and RNA Interference......Page 726
  piRNAs Protect the Genome for Future Generations......Page 727
  RNA-Induced Transcriptional Silencing......Page 728
  lncRNAs Mediate Transcriptional Repression by Interacting with Chromatin-Regulating Complexes......Page 729
  Circular RNAs Act as “Sponges” to Soak Up MicroRNAs......Page 730
 mRNA Localization and Translational Regulation in Eukaryotes......Page 733
  VNTR-Based DNA Fingerprinting......Page 736
  Autosomal STR DNA Profiling......Page 738
  Y-Chromosome STR Profiling......Page 739
  Mitochondrial DNA Profiling......Page 740
  Single-Nucleotide Polymorphism Profiling......Page 741
 Interpreting DNA Profiles......Page 742
  The Uniqueness of DNA Profiles......Page 743
  DNA Profile Databases......Page 744
 Technical and Ethical Issues Surrounding DNA Profiling......Page 745
 Personalized Medicine and Pharmacogenomics......Page 747
  Optimizing Drug Therapies......Page 748
  Reducing Adverse Drug Reactions......Page 750
 Personalized Medicine and Disease Diagnostics......Page 751
  Personal Genomics and Cancer......Page 753
  Personal Genomics and Disease Diagnosis: Analyzing One Genome......Page 754
 Technical, Social, and Ethical Challenges......Page 755
Genetically Modified Foods......Page 759
  Herbicide-Resistant GM Crops......Page 760
  Insect-Resistant GM Crops......Page 761
  GM Crops for Direct Consumption......Page 762
 Methods Used to Create GM Plants......Page 764
  Roundup-Ready® Soybeans......Page 766
 GM Foods Controversies......Page 767
  Health and Safety......Page 768
  Environmental Effects......Page 769
 The Future of GM Foods......Page 770
 What Genetic Conditions Are Candidates for Treatment by Gene Therapy?......Page 773
  Viral Vectors for Gene Therapy......Page 774
 The First Successful Gene Therapy Trial......Page 777
 Gene Therapy Setbacks......Page 778
  Treating Retinal Blindness......Page 779
  HIV as a Vector Shows Promise in Recent Trials......Page 780
  DNA-Editing Nucleases for Gene Targeting......Page 782
  RNA Silencing for Gene Inhibition......Page 783
  Ethical Concerns Surrounding Gene Therapy......Page 785
Appendix A: Selected Readings......Page 788
Appendix B: Answers to Selected Problems......Page 800
Glossary......Page 842
Credits......Page 864
Index......Page 868
 Nobel Laureates......Page 891
Back Cover......Page 894