Concepts of Genetics

Cover......Page 1
Brief Contents......Page 2
Half Title Page......Page 5
Title Page......Page 7
Copyright Page......Page 8
About The Authors......Page 9
Brief Contents......Page 11
Contents......Page 19
Preface......Page 35
Chapter 1 Introduction to Genetics......Page 43
1.1 Genetics Has a Rich and Interesting History......Page 44
Mendel’s Work on Transmission of Traits......Page 45
The Chromosome Theory of Inheritance: Uniting Mendel and Meiosis......Page 46
The Search for the Chemical Nature of Genes: DNA or Protein?......Page 47
Gene Expression: From DNA to Phenotype......Page 48
Linking Genotype to Phenotype: Sickle‐Cell Anemia......Page 49
Plants, Animals, and the Food Supply......Page 50
1.6 Genomics, Proteomics, and Bioinformatics Are New and Expanding Fields......Page 51
1.7 Genetic Studies Rely on the Use of Model Organisms......Page 52
Model Organisms and Human Diseases......Page 53
Genetics, Ethics, and Society......Page 54
Problems and Discussion Questions......Page 55
Chapter 2 Mitosis and Meiosis......Page 56
2.1 Cell Structure Is Closely Tied to Genetic Function......Page 57
2.2 Chromosomes Exist in Homologous Pairs in Diploid Organisms......Page 59
Interphase and the Cell Cycle......Page 61
Prometaphase and Metaphase......Page 62
Telophase......Page 64
2.4 Meiosis Creates Haploid Gametes and Spores and Enhances Genetic Variation in Species......Page 65
Metaphase, Anaphase, and Telophase I......Page 67
The Second Meiotic Division......Page 69
2.6 Meiosis Is Critical to Sexual Reproduction in All Diploid Organisms......Page 71
2.7 Electron Microscopy Has Revealed the Physical Structure of Mitotic and Meiotic Chromosomes......Page 72
EXPLORING GENOMICS: PubMed: Exploring and Retrieving Biomedical Literature......Page 73
Insights and Solutions......Page 74
Problems and Discussion Questions......Page 76
Chapter 3 Mendelian Genetics......Page 78
3.1 Mendel Used a Model Experimental Approach to Study Patterns of Inheritance......Page 79
Mendel’s First Three Postulates......Page 80
Modern Genetic Terminology......Page 81
The Testcross: One Character......Page 82
Mendel’s Fourth Postulate: Independent Assortment......Page 83
The Testcross: Two Characters......Page 86
The Forked‐Line Method, or Branch Diagram......Page 87
Unit Factors, Genes, and Homologous Chromosomes......Page 88
3.7 Laws of Probability Help to Explain Genetic Events......Page 90
3.8 Chi‐Square Analysis Evaluates the Influence of Chance on Genetic Data......Page 91
Chi‐Square Calculations and the Null Hypothesis......Page 92
Interpreting Probability Values......Page 93
Pedigree Conventions......Page 94
Pedigree Analysis......Page 95
How Mendel’s Peas Become Wrinkled: A Molecular Explanation......Page 96
EXPLORING GENOMICS: Online Mendelian Inheritance in Man......Page 97
Summary Points......Page 98
Insights and Solutions......Page 99
Problems and Discussion Questions......Page 100
Chapter 4 Extensions of Mendelian Genetics......Page 104
4.1 Alleles Alter Phenotypes in Different Ways......Page 105
4.3 Neither Allele Is Dominant in Incomplete, or Partial, Dominance......Page 106
4.4 In Codominance, the Influence of Both Alleles in a Heterozygote Is Clearly Evident......Page 107
The A and B Antigens......Page 108
The Bombay Phenotype......Page 109
The white Locus in Drosophila......Page 110
4.6 Lethal Alleles Represent Essential Genes......Page 111
Evolving Concept of the Gene......Page 112
Epistasis......Page 113
Novel Phenotypes......Page 117
4.9 Complementation Analysis Can Determine if Two Mutations Causing a Similar Phenotype Are Alleles of the Same Gene......Page 119
4.10 Expression of a Single Gene May Have Multiple Effects......Page 120
X‐Linkage in Drosophila......Page 121
X‐Linkage in Humans......Page 122
4.12 In Sex‐Limited and Sex‐Influenced Inheritance, an Individual’s Sex Influences the Phenotype......Page 123
Penetrance and Expressivity......Page 124
Temperature Effects—An Introduction to Conditional Mutations......Page 125
Onset of Genetic Expression......Page 126
GENETICS, ETHICS, AND SOCIETY: Nature versus Nurture: Is the Debate Over?......Page 127
Summary Points......Page 128
Insights and Solutions......Page 129
Problems and Discussion Questions......Page 131
Chapter 5 Chromosome Mapping in Eukaryotes......Page 136
5.1 Genes Linked on the Same Chromosome Segregate Together......Page 137
The Linkage Ratio......Page 138
Sturtevant and Mapping......Page 140
Single Crossovers......Page 142
Multiple Exchanges......Page 143
Three‐Point Mapping in Drosophila......Page 144
Determining the Gene Sequence......Page 146
An Autosomal Mapping Problem in Maize......Page 148
Interference and the Coefficient of Coincidence......Page 151
Evolving Concept of the Gene......Page 152
5.6 Lod Score Analysis and Somatic Cell Hybridization Were Historically Important in Creating Human Chromosome Maps......Page 153
5.7 Chromosome Mapping Is Currently Performed Using DNA Markers and Annotated Computer Databases......Page 155
5.8 Crossing Over Involves a Physical Exchange between Chromatids......Page 156
5.9 Exchanges Also Occur between Sister Chromatids during Mitosis......Page 157
CASE STUDY Links to autism......Page 158
Insights and Solutions......Page 159
Problems and Discussion Questions......Page 161
Extra‐Spicy Problems......Page 163
Chapter 6 Genetic Analysis and Mapping in Bacteria and Bacteriophages......Page 165
6.1 Bacteria Mutate Spontaneously and Grow at an Exponential Rate......Page 166
Conjugation in Bacteria: The Discovery of F+ and F– Strains......Page 167
Hfr Bacteria and Chromosome Mapping......Page 169
The F' State and Merozygotes......Page 172
6.3 The F Factor Is an Example of a Plasmid......Page 174
6.4 Transformation Is a Second Process Leading to Genetic Recombination in Bacteria......Page 175
Transformation and Linked Genes......Page 176
Phage T4: Structure and Life Cycle......Page 177
The Plaque Assay......Page 178
Lysogeny......Page 179
The Lederberg–Zinder Experiment......Page 180
Bacteriophage Mutations......Page 181
Mapping in Bacteriophages......Page 182
The rII Locus of Phage T4......Page 183
Complementation by rII Mutations......Page 184
Deletion Testing of the rII Locus......Page 185
Evolving Concept of the Gene......Page 186
GENETICS, ETHICS, AND SOCIETY: Multidrug‐Resistant Bacteria: Fighting with Phage......Page 187
CASE STUDY To treat or not to treat......Page 188
Insights and Solutions......Page 189
Problems and Discussion Questions......Page 190
Extra‐Spicy Problems......Page 191
Chapter 7 Sex Determination and Sex Chromosomes......Page 193
7.2 The Y Chromosome Determines Maleness in Humans......Page 194
Klinefelter and Turner Syndromes......Page 195
47,XYY Condition......Page 196
The Y Chromosome and Male Development......Page 197
7.3 The Ratio of Males to Females in Humans Is Not 1.0......Page 200
Barr Bodies......Page 201
The Lyon Hypothesis......Page 202
The Mechanism of Inactivation......Page 203
D. melanogaster......Page 205
Caenorhabditis elegans......Page 206
Drosophila Sxl Gene Induces Female Development......Page 207
7.6 Temperature Variation Controls Sex Determination in Many Reptiles......Page 208
GENETICS, ETHICS, AND SOCIETY: A Question of Gender: Sex Selection in Humans......Page 209
Insights and Solutions......Page 210
Problems and Discussion Questions......Page 211
Extra‐Spicy Problems......Page 212
Chapter 8 Chromosomal Mutations: Variation in Number and Arrangement......Page 213
Monosomy......Page 214
Trisomy......Page 215
The Down Syndrome Critical Region (DSCR)......Page 216
MODERN APPROACHES TO UNDERSTANDING GENE FUNCTION: Mouse Models of Down Syndrome......Page 217
The Origin of the Extra Chromosome 21 in Down Syndrome......Page 218
Human Aneuploidy......Page 219
Autopolyploidy......Page 220
Allopolyploidy......Page 221
8.4 Variation Occurs in the Composition and Arrangement of Chromosomes......Page 223
Cri du Chat Syndrome in Humans......Page 224
8.6 A Duplication Is a Repeated Segment of a Chromosome......Page 225
The Bar Mutation in Drosophila......Page 226
Duplications at the Molecular Level: Copy Number Variations (CNVs)......Page 227
Consequences of Inversions during Gamete Formation......Page 228
Evolutionary Advantages of Inversions......Page 229
8.8 Translocations Alter the Location of Chromosomal Segments in the Genome......Page 230
Translocations in Humans: Familial Down Syndrome......Page 231
Fragile‐X Syndrome......Page 232
GENETICS, ETHICS, AND SOCIETY: Down Syndrome and Prenatal Testing—The New Eugenics?......Page 233
Summary Points......Page 234
Problems and Discussion Questions......Page 235
Extra‐Spicy Problems......Page 236
Chapter 9 Extranuclear Inheritance......Page 238
Chloroplast Mutations in Chlamydomonas......Page 239
Mitochondrial Mutations: Early Studies in Neurospora and Yeast......Page 240
Organelle DNA and the Endosymbiotic Theory......Page 242
Molecular Organization and Gene Products of Chloroplast DNA......Page 243
Molecular Organization and Gene Products of Mitochondrial DNA......Page 244
9.3 Mutations in Mitochondrial DNA Cause Human Disorders......Page 245
Mitochondria, Human Health, and Aging......Page 246
Future Prevention of the Transmission of mtDNA‐Based Disorders......Page 247
9.4 In Maternal Effect, the Maternal Genotype Has a Strong Influence during Early Development......Page 248
Lymnaea Coiling......Page 249
Embryonic Development in Drosophila......Page 250
CASE STUDY Is it all in the genes?......Page 251
Insights and Solutions......Page 252
Problems and Discussion Questions......Page 253
Extra‐Spicy Problems......Page 254
Chapter 10 DNA Structure and Analysis......Page 255
10.2 Until 1944, Observations Favored Protein as the Genetic Material......Page 256
Transformation: Early Studies......Page 257
Transformation: The Avery, MacLeod, and McCarty Experiment......Page 258
The Hershey–Chase Experiment......Page 260
Indirect Evidence: Distribution of DNA......Page 262
10.5 RNA Serves as the Genetic Material in Some Viruses......Page 263
Nucleotides: Building Blocks of Nucleic Acids......Page 264
Nucleoside Diphosphates and Triphosphates......Page 265
Polynucleotides......Page 266
Base‐Composition Studies......Page 267
The Watson–Crick Model......Page 268
10.9 The Structure of RNA Is Chemically Similar to DNA, but Single Stranded......Page 271
Electrophoresis......Page 273
EXPLORING GENOMICS: Introduction to Bioinformatics: BLAST......Page 275
Insights and Solutions......Page 276
Problems and Discussion Questions......Page 277
Extra‐Spicy Problems......Page 278
Chapter 11 DNA Replication and Recombination......Page 280
11.1 DNA Is Reproduced by Semiconservative Replication......Page 281
The Meselson–Stahl Experiment......Page 282
Semiconservative Replication in Eukaryotes......Page 283
Origins, Forks, and Units of Replication......Page 284
DNA Polymerase I......Page 285
DNA Polymerase II, III, IV, and V......Page 286
The DNA Pol III Holoenzyme......Page 287
Unwinding the DNA Helix......Page 288
Continuous and Discontinuous DNA Synthesis......Page 289
Proofreading and Error Correction Occurs during DNA Replication......Page 290
11.4 A Coherent Model Summarizes DNA Replication......Page 291
MODERN APPROACHES TO UNDERSTANDING GENE FUNCTION: Lethal Knockouts......Page 292
Initiation at Multiple Replication Origins......Page 293
Multiple Eukaryotic DNA Polymerases......Page 294
11.7 Telomeres Solve Stability and Replication Problems at Eukaryotic Chromosome Ends......Page 295
Telomeres and Chromosome End Replication......Page 296
Models of Homologous Recombination......Page 298
GENETICS, ETHICS, AND SOCIETY: Telomeres: The Key to a Long Life?......Page 300
Summary Points......Page 301
Problems and Discussion Questions......Page 302
Extra‐Spicy Problems......Page 303
Chapter 12 DNA Organization in Chromosomes......Page 305
12.1 Viral and Bacterial Chromosomes are Relatively Simple DNA Molecules......Page 306
12.2 Supercoiling Facilitates Compaction of the DNA of Viral and Bacterial Chromosomes......Page 307
Polytene Chromosomes......Page 309
Lampbrush Chromosomes......Page 310
Chromatin Structure and Nucleosomes......Page 311
Chromatin Remodeling......Page 313
12.5 Chromosome Banding Differentiates Regions along the Mitotic Chromosome......Page 315
12.6 Eukaryotic Genomes Demonstrate Complex Sequence Organization Characterized by Repetitive DNA......Page 316
Satellite DNA......Page 317
Middle Repetitive Sequences: VNTRs and STRs......Page 318
12.7 The Vast Majority of a Eukaryotic Genome Does Not Encode Functional Genes......Page 319
EXPLORING GENOMICS: Database of Genomic Variants: Structural Variations in the Human Genome......Page 320
Insights and Solutions......Page 321
Problems and Discussion Questions......Page 322
Extra‐Spicy Problems......Page 323
Chapter 13 The Genetic Code and Transcription......Page 325
13.2 Early Studies Established the Basic Operational Patterns of the Code......Page 326
Synthesizing Polypeptides in a Cell‐Free System......Page 327
The Use of Mixed Heteropolymers......Page 328
Repeating Copolymers......Page 330
Degeneracy and the Wobble Hypothesis......Page 332
Punctuating the Code: Initiation and Termination Codons......Page 333
13.6 The Genetic Code Is Nearly Universal......Page 334
13.8 Transcription Synthesizes RNA on a DNA Template......Page 335
Promoters, Template Binding, and the Subunit......Page 336
Initiation, Elongation, and Termination of RNA Synthesis in Bacteria......Page 338
13.10 Transcription in Eukaryotes Differs from Bacterial Transcription in Several Ways......Page 339
Initiation of Transcription in Eukaryotes......Page 340
Recent Discoveries Concerning Eukaryotic RNA Polymerase Function......Page 341
Processing Eukaryotic RNA: Caps and Tails......Page 342
13.11 The Coding Regions of Eukaryotic Genes Are Interrupted by Intervening Sequences Called Introns......Page 343
Splicing Mechanisms: Self‐Splicing RNAs......Page 344
Splicing Mechanisms: The Spliceosome......Page 345
13.12 RNA Editing May Modify the Final Transcript......Page 346
13.13 Transcription Has Been Visualized by Electron Microscopy......Page 348
GENETICS, ETHICS, AND SOCIETY: Treating Duchenne Muscular Dystrophy with Exon‐Skipping Drugs......Page 349
Insights and Solutions......Page 350
Problems and Discussion Questions......Page 351
Extra‐Spicy Problems......Page 352
14.1 Translation of mRNA Depends on Ribosomes and Transfer RNAs......Page 354
Ribosomal Structure......Page 355
tRNA Structure......Page 356
Charging tRNA......Page 357
Initiation......Page 358
Elongation......Page 360
Polyribosomes......Page 361
14.3 High‐Resolution Studies Have Revealed Many Details about the Functional Bacterial Ribosome......Page 362
14.4 Translation Is More Complex in Eukaryotes......Page 363
14.5 The Initial Insight That Proteins Are Important in Heredity Was Provided by the Study of Inborn Errors of Metabolism......Page 364
Phenylketonuria......Page 365
Genes and Enzymes: Analysis of Biochemical Pathways......Page 366
Sickle‐Cell Anemia......Page 368
14.8 Variation in Protein Structure Provides the Basis of Biological Diversity......Page 370
Protein Folding and Misfolding......Page 374
14.10 Proteins Perform Many Diverse Roles......Page 375
Exon Shuffling......Page 376
EXPLORING GENOMICS: Translation Tools and Swiss‐Prot for Studying Protein Sequences......Page 377
CASE STUDY Crippled ribosomes......Page 378
Problems and Discussion Questions......Page 379
Extra‐Spicy Problems......Page 381
Chapter 15 Gene Mutation, DNA Repair, and Transposition......Page 382
Classification Based on Type of Molecular Change......Page 383
Classification Based on Location of Mutation......Page 384
15.2 Mutations Occur Spontaneously and Randomly......Page 385
Spontaneous Germ‐Line Mutation Rates in Humans......Page 386
The Fluctuation Test: Are Mutations Random or Adaptive?......Page 387
Tautomeric Shifts......Page 388
Oxidative Damage......Page 389
15.4 Induced Mutations Arise from DNA Damage Caused by Chemicals and Radiation......Page 390
Alkylating, Intercalating, and Adduct‐Forming Agents......Page 391
Ionizing Radiation......Page 392
Single‐Gene Mutations and β‐Thalassemia......Page 394
Mutations Caused by Expandable DNA Repeats......Page 395
Proofreading and Mismatch Repair......Page 396
Base and Nucleotide Excision Repair......Page 397
Nucleotide Excision Repair and Xeroderma ‐Pigmentosum in Humans......Page 399
Double‐Strand Break Repair in Eukaryotes......Page 400
15.7 The Ames Test Is Used to Assess the ‐Mutagenicity of Compounds......Page 401
DNA Transposons......Page 402
DNA Transposons—the Ac–Ds System in Maize......Page 404
Retrotransposons......Page 405
Retrotransposons—the Copia –White‐Apricot ‐System in Drosophila......Page 406
Transposable Elements in Humans......Page 407
MODERN APPROACHES TO UNDERSTANDING GENE FUNCTION: Transposon‐Mediated Mutations Reveal Genes Involved in Colorectal Cancer......Page 408
Transposable Elements, Mutations, and Evolution......Page 409
EXPLORING GENOMICS: Sequence Alignment to Identify a Mutation......Page 410
Insights and Solutions......Page 411
Problems and Discussion Questions......Page 412
Extra‐Spicy Problems......Page 413
Chapter 16 Regulation of Gene Expression in Bacteria......Page 415
Structural Genes......Page 416
The Discovery of Regulatory Mutations......Page 417
The Operon Model: Negative Control......Page 418
Isolation of the Repressor......Page 420
16.3 The Catabolite‐Activating Protein (CAP) Exerts Positive Control over the lac Operon......Page 421
16.4 Crystal Structure Analysis of Repressor ‐Complexes Has Confirmed the Operon Model......Page 423
Evolving Concept of the Gene......Page 425
16.6 RNA Plays Diverse Roles in Regulating Gene Expression in Bacteria......Page 426
Attenuation......Page 427
Riboswitches......Page 428
Small Noncoding RNAs Play Regulatory Roles in Bacteria......Page 429
GENETICS, ETHICS, AND SOCIETY: Quorum Sensing: Social Networking and Gene Regulation in Bacteria......Page 430
Insights and Solutions......Page 431
Problems and Discussion Questions......Page 432
Extra‐Spicy Problems......Page 433
Chapter 17 Transcriptional Regulation in Eukaryotes......Page 435
17.1 Organization of the Eukaryotic Cell Facilitates Gene Regulation at Several Levels......Page 436
Chromosome Territories and Transcription Factories......Page 437
Histone Modifications and Chromatin Remodeling......Page 438
DNA Methylation......Page 439
Promoters and Promoter Elements......Page 440
17.4 Eukaryotic Transcription Initiation Is Regulated by Transcription Factors That Bind to Cis‐Acting Sites......Page 442
The Human Metallothionein 2A Gene: Multiple Cis‐Acting Elements and Transcription Factors......Page 443
Formation of the RNA Polymerase II Transcription Initiation Complex......Page 444
Mechanisms of Transcription Activation and Repression......Page 445
17.6 Gene Regulation in a Model Organism: Transcription of the GAL Genes of Yeast......Page 446
Enhancer and Promoter Elements......Page 448
Many Disease‐Associated Genome Variations Affect Regulatory Regions......Page 449
EXPLORING GENOMICS: Tissue‐Specific Gene Expression......Page 450
Summary Points......Page 451
Insights and Solutions......Page 452
Extra‐Spicy Problems......Page 453
Chapter 18 Posttranscriptional Regulation in Eukaryotes......Page 455
Types of Alternative Splicing......Page 456
Regulation of Alternative Splicing......Page 458
Sex Determination in Drosophila: A Model for Regulation of Alternative Splicing......Page 459
Alternative Splicing and Human Diseases......Page 460
Mechanisms of mRNA Decay......Page 461
18.3 Noncoding RNAs Play Diverse Roles in ‐Posttranscriptional Regulation......Page 462
MODERN APPROACHES TO UNDERSTANDING GENE FUNCTION: MicroRNAs Regulate Ovulation in Female Mice......Page 463
Mechanisms of RNA Interference......Page 464
Long Noncoding RNAs and Posttranscriptional Regulation......Page 466
18.4 mRNA Localization and Translation Initiation Are Highly Regulated......Page 467
mRNA Localization and Localized Translational Control......Page 468
Regulation of Proteins by Phosphorylation......Page 469
Ubiquitin‐Mediated Protein Degradation......Page 470
GENETICS, ETHICS, AND SOCIETY: Is DNA Enough?......Page 471
Insights and Solutions......Page 472
Problems and Discussion Questions......Page 473
Extra‐Spicy Problems......Page 474
Chapter 19 Epigenetic Regulation of Gene Expression......Page 475
DNA Methylation and the Methylome......Page 476
Histone Modification and Chromatin Remodeling......Page 478
Short and Long Noncoding RNAs......Page 481
Parent‐of‐Origin Monoallelic Expression: Imprinting......Page 482
Random Monoallelic Expression of Autosomal Genes......Page 484
Assisted Reproductive Technologies (ART) and Imprinting Defects......Page 485
DNA Methylation and Cancer......Page 486
Chromatin Remodeling and Histone Modification in Cancer......Page 487
Environmental Induction of Epigenetic Change......Page 488
19.5 Epigenome Projects and Databases......Page 490
Summary Points......Page 492
EXPLORING GENOMICS: The International Human Epigenome Consortium (IHEC)......Page 493
Problems and Discussion Questions......Page 494
Extra‐Spicy Problems......Page 495
Chapter 20 Recombinant DNA Technology......Page 496
Restriction Enzymes Cut DNA at Specific ‐Recognition Sequences......Page 497
DNA Vectors Accept and Replicate DNA Molecules to Be Cloned......Page 498
Bacterial Plasmid Vectors......Page 499
Other Types of Cloning Vectors......Page 501
Host Cells for Cloning Vectors......Page 502
Complementary DNA (cDNA) Libraries......Page 503
20.3 The Polymerase Chain Reaction Is a Powerful Technique for Copying DNA......Page 504
PCR Applications......Page 506
Nucleic Acid Blotting......Page 508
In Situ Hybridization......Page 510
20.5 DNA Sequencing Is the Ultimate Way to Characterize DNA at the Molecular Level......Page 511
Next‐Generation Sequencing Technology......Page 513
Third‐Generation Sequencing Technology......Page 514
20.6 Creating Knockout and Transgenic Organisms for Studying Gene Function......Page 515
Gene Targeting and Knockout Animal Models......Page 516
Making a Transgenic Animal: The Basics......Page 519
Gene Editing with CRISPR‐Cas......Page 520
EXPLORING GENOMICS: Manipulating Recombinant DNA: Restriction Mapping and Designing PCR Primers......Page 521
Summary Points......Page 522
Problems and Discussion Questions......Page 523
Extra‐Spicy Problems......Page 525
Chapter 21 Genomic Analysis......Page 527
21.2 Whole‐Genome Sequencing Is Widely Used for Sequencing and Assembling Entire Genomes......Page 528
High‐Throughput Sequencing and Its Impact on Genomics......Page 529
The Clone‐by‐Clone Approach......Page 530
21.3 DNA Sequence Analysis Relies on Bioinformatics Applications and Genome Databases......Page 531
Annotation to Identify Gene Sequences......Page 532
Hallmark Characteristics of a Gene Sequence Can Be Recognized during Annotation......Page 533
Predicting Gene and Protein Functions by Sequence Analysis......Page 535
Investigators Are Using Genomics Techniques Such as Chromatin Immunoprecipitation to Investigate Aspects of Genome Function and Regulation......Page 536
Origins of the Project......Page 537
Major Features of the Human Genome......Page 538
Accessing the Human Genome Project on the Internet......Page 539
Personal Genome Projects......Page 541
Somatic Genome Mosaicism and the Emerging Pangenome......Page 542
Whole‐Exome Sequencing......Page 543
Encyclopedia of DNA Elements (ENCODE) Project......Page 544
Stone‐Age Genomics......Page 545
Bacterial and Eukaryotic Genomes Display Common Structural and Functional Features and Important Differences......Page 546
The Dog Genome......Page 548
The Chimpanzee Genome......Page 549
The Neanderthal Genome and Modern Humans......Page 550
The Human Microbiome Project......Page 551
21.9 Transcriptome Analysis Reveals Profiles of Expressed Genes in Cells and Tissues......Page 552
DNA Microarray Analysis......Page 553
RNA Sequencing Technology Allows for In Situ Analysis of Gene Expression......Page 554
Reconciling the Number of Genes and the Number of Proteins Expressed by a Cell or Tissue......Page 555
Mass Spectrometry for Protein Identification......Page 557
EXPLORING GENOMICS: Contigs, Shotgun Sequencing, and Comparative Genomics......Page 559
Insights and Solutions......Page 560
Problems and Discussion Questions......Page 561
Extra‐Spicy Problems......Page 562
Chapter 22 Applications of Genetic Engineering and Biotechnology......Page 563
Recombinant Protein Production in Bacteria......Page 564
Recombinant DNA Approaches for Vaccine Production......Page 566
DNA‐Based Vaccines......Page 567
22.3 Genetically Modified Animals Serve Important Roles in Biotechnology......Page 568
Examples of Transgenic Animals......Page 569
Prenatal Genetic Testing......Page 571
Genetic Testing Using Allele‐Specific Oligonucleotides......Page 572
Genetic Testing Using Microarrays......Page 574
Applications of Gene‐Expression Microarrays and Next–Generation Sequencing for Pathogen Identification......Page 578
22.5 Genetic Analysis of Individual Genomes......Page 579
22.6 Genetic Analysis from Single Cells......Page 580
22.7 Genome‐Wide Association Studies Identify Genome Variations That Contribute to Disease......Page 581
Design and Transplantation of a Synthetic Genome Defines the Minimal Bacterial Genome......Page 584
The Essential Genes of Human Cells and the Quest to Create a Synthetic Human Genome......Page 586
Synthetic Biology for Bioengineering Applications......Page 587
Genetic Testing and Ethical Dilemmas......Page 588
Direct‐to‐Consumer Genetic Testing and Regulating the Genetic Test Providers......Page 589
DNA and Gene Patents......Page 590
GENETICS, ETHICS, AND SOCIETY: Privacy and Anonymity in the Era of Genomic Big Data......Page 591
Patents and Synthetic Biology......Page 592
Insights and Solutions......Page 593
Problems and Discussion Questions......Page 594
23.1 Differentiated States Develop from Coordinated Programs of Gene Expression......Page 597
Genetic and Epigenetic Regulation of Development......Page 598
Analysis of Developmental Mechanisms......Page 599
Genetic Analysis of Embryogenesis......Page 600
Segment Polarity Genes......Page 603
Segmentation Genes in Mice and Humans......Page 604
Hox Genes in Drosophila......Page 605
Hox Genes and Human Genetic Disorders......Page 607
Homeotic Genes in Arabidopsis......Page 608
Divergence in Homeotic Genes......Page 609
The Notch Signaling Pathway......Page 610
MODERN APPROACHES TO UNDERSTANDING GENE FUNCTION: Downregulating a Single Gene Reveals Secrets to Head Regeneration in Planaria......Page 611
Overview of C. elegans Development......Page 612
Genetic Analysis of Vulva Formation......Page 613
The Control of Eye Formation......Page 614
GENETICS, ETHICS, AND SOCIETY: Stem Cell Wars......Page 617
Insights and Solutions......Page 618
Problems and Discussion Questions......Page 619
Extra Spicy Problems......Page 620
Chapter 24 Cancer Genetics......Page 621
The Clonal Origin of Cancer Cells......Page 622
Cancer as a Multistep Process, Requiring Multiple Mutations and Clonal Expansions......Page 623
24.2 Cancer Cells Contain Genetic Defects Affecting Genomic Stability, DNA Repair, and Chromatin Modifications......Page 624
Genomic Instability and Defective DNA Repair......Page 625
The Cell Cycle and Signal Transduction......Page 626
Cell‐Cycle Control and Checkpoints......Page 627
Control of Apoptosis......Page 628
24.4 Proto‐oncogenes and Tumor‐Suppressor Genes Are Altered in Cancer Cells......Page 629
The ras Proto‐oncogenes......Page 630
The TP53 Tumor‐Suppressor Gene......Page 631
24.6 Predisposition to Some Cancers Can Be Inherited......Page 632
24.7 Viruses Contribute to Cancer in Both Humans and Animals......Page 633
Human‐Made Chemicals and Pollutants......Page 635
CASE STUDY Cancer‐killing bacteria......Page 636
EXPLORING GENOMICS: The Cancer Genome Anatomy Project (CGAP)......Page 637
Problems and Discussion Questions......Page 638
Extra Spicy Problems......Page 639
Chapter 25 Quantitative Genetics and Multifactorial Traits......Page 641
The Multiple‐Gene Hypothesis for Quantitative Inheritance......Page 642
Additive Alleles: The Basis of Continuous Variation......Page 643
Calculating the Number of Polygenes......Page 644
Variance......Page 645
Analysis of a Quantitative Character......Page 646
25.4 Heritability Values Estimate the Genetic Contribution to Phenotypic Variability......Page 647
Artificial Selection......Page 649
25.5 Twin Studies Allow an Estimation of Heritability in Humans......Page 651
Twin Studies Have Several Limitations......Page 652
25.6 Quantitative Trait Loci Are Useful in Studying Multifactorial Phenotypes......Page 653
Expression QTLs Regulate Gene Expression......Page 655
Expression QTLs and Genetic Disorders......Page 656
GENETICS, ETHICS, AND SOCIETY: Rice, Genes, and the Second Green Revolution......Page 657
Summary Points......Page 658
Insights and Solutions......Page 659
Problems and Discussion Questions......Page 660
Extra‐Spicy Problems......Page 661
Chapter 26 Population and Evolutionary Genetics......Page 663
Genetic Variation in Genomes......Page 664
26.2 The Hardy–Weinberg Law Describes Allele Frequencies and Genotype Frequencies in Population Gene Pools......Page 665
The Hardy–Weinberg Law and Its Assumptions......Page 666
26.3 The Hardy–Weinberg Law Can Be Applied to Human Populations......Page 667
Testing for Hardy–Weinberg Equilibrium in a Population......Page 668
Calculating Allele Frequencies for X‐linked Traits......Page 670
Calculating Heterozygote Frequency......Page 671
Fitness and Selection......Page 672
There Are Several Types of Selection......Page 673
26.6 Migration and Gene Flow Can Alter Allele Frequencies......Page 676
26.7 Genetic Drift Causes Random Changes in Allele Frequency in Small Populations......Page 677
Inbreeding......Page 678
Changes Leading to Speciation......Page 680
The Rate of Macroevolution and Speciation......Page 681
Constructing Phylogenetic Trees from DNA Sequences......Page 682
Molecular Clocks Measure the Rate of Evolutionary Change......Page 683
The Complex Origins of the Human Genome......Page 684
CASE STUDY A Tale of Two Olivias......Page 686
Insights and Solutions......Page 687
Problems and Discussion Questions......Page 688
Extra‐Spicy Problems......Page 689
CRISPR‐Cas Is an Adaptive Immune System in Prokaryotes......Page 691
The CRISPR‐Cas Mechanism for RNA‐Guided Destruction of Invading DNA......Page 692
Type II CRISPR‐Cas Systems......Page 693
CRISPR‐Cas9 Genome Editing of Mammalian Cells......Page 694
CRISPR-Cas as a Tool for Basic Genetic Research......Page 696
Box 1 CRISPR‐Cas as a Tool for Basic Genetic Research......Page 697
CRISPR‐Cas in Biotechnology......Page 698
Clinical Use of CRISPR‐Cas to Treat or Cure Disease......Page 699
Box 2 Ethical Concerns of Human Genome Editing......Page 700
VNTR‐Based DNA Fingerprinting......Page 703
Box 1 The Pitchfork Case: The First Criminal Conviction Using DNA Profiling......Page 704
Autosomal STR DNA Profiling......Page 705
Mitochondrial DNA Profiling......Page 706
DNA Phenotyping......Page 708
Interpreting DNA Profiles......Page 709
The Uniqueness of DNA Profiles......Page 710
Box 3 The Kennedy Brewer Case: Two Bite‐Mark Errors and One Hit......Page 711
Box 4 A Case of Transference: The Lukis Anderson Story......Page 712
Optimizing Drug Responses......Page 714
Developing Targeted Drugs......Page 715
Box 1 Preemptive Pharmacogenomic Screening: The PGEN4Kids Program......Page 716
Targeted Cancer Immunotherapies......Page 717
Box 2 Precision Cancer Diagnostics and Treatments: The Lukas Wartman Story......Page 718
Box 3 Cell Types in the Innate and Adaptive Immune Systems......Page 719
Box 4 Steps in Cytotoxic T‐cell Recognition, Activation, and Destruction of Cancer Cells......Page 720
Technical, Social, and Ethical Challenges......Page 722
Box 5 Beyond Genomics: Personal Omics Profiling......Page 723
What Are GM Foods?......Page 725
Herbicide‐Resistant GM Crops......Page 726
Insect‐Resistant GM Crops......Page 727
GM Crops for Direct Consumption......Page 728
Selectable Markers......Page 729
Roundup‐Ready® Soybeans......Page 730
Gene Editing and GM Foods......Page 731
GM Foods Controversies......Page 732
Health and Safety......Page 733
Environmental Effects......Page 734
The Future of GM Foods......Page 735
What Genetic Conditions Are Candidates for Treatment by Gene Therapy?......Page 737
Viral Vectors for Gene Therapy......Page 738
Box 1 ClinicalTrials.gov......Page 739
Stem Cells for Delivering Therapeutic Genes......Page 740
The First Successful Gene Therapy Trial......Page 741
Problems with Gene Therapy Vectors......Page 742
Successful Treatment of Hemophilia B......Page 743
Box 2 Glybera Is the First Commercial Gene Therapy to be Approved in the West Lasted Only 5 Years......Page 744
DNA‐Editing Nucleases......Page 745
CRISPR‐Cas Method Revolutionizes Gene Editing Applications and Renews Optimism in Gene Therapy......Page 746
RNA‐Based Therapeutics......Page 748
Future Challenges and Ethical Issues......Page 749
Box 3 Gene Doping for Athletic Performance?......Page 750
Advances in Neurogenetics: The Study of Huntington Disease......Page 752
Box 2 Nancy Wexler and the Venezuelan Pedigree......Page 753
Assigning the HD Gene to Chromosome 4......Page 754
The Identification and Cloning of the Huntington Gene......Page 755
The HTT Gene and Its Protein Product......Page 756
Synaptic Dysfunction......Page 757
Using Transgenic Mice to Study Huntington Disease......Page 759
Identifying Potential Drugs for Therapy......Page 760
Gene Silencing to Reduce mHTT Levels......Page 761
Gene Editing in Huntington Disease......Page 762
Box 4 Huntington Disease and Behavior......Page 763
Appendix A: Selected Readings......Page 767
Appendix B: Answers to Selected Problems......Page 781
Glossary......Page 825
Credits......Page 845
Index......Page 849
Evolving Concept of The Gene......Page 867