Genetics and Genomics MBLG2072 (Custom Edition)

Table of Contents
2 Transmission Genetics 25
2.1 Gregor Mendel Discovered the
Basic Principles of Genetic
Transmission 26
Mendel’s Modern Experimental
Approach 27
Five Critical Experimental Innovations 28
2.2 Monohybrid Crosses Reveal the
Segregation of Alleles 30
Identifying Dominant and Recessive
Traits 30
Evidence of Particulate Inheritance and
Rejection of the Blending Theory 31
Segregation of Alleles 32
Hypothesis Testing by Test-Cross
Analysis 33
Hypothesis Testing by F2 Self-Fertilization 34
2.3 Dihybrid and Trihybrid Crosses Reveal
the Independent Assortment of
Alleles 35
Dihybrid-Cross Analysis of Two Genes 35
Genetic Analysis 2.1 36
Testing Independent Assortment by Test-Cross
Analysis 38
Genetic Analysis 2.2 39
Testing Independent Assortment by Trihybrid-
Cross Analysis 40
Probability Calculations in Genetics Problem
Solving 41
The Rediscovery of Mendel’s Work 42
Experimental Insight 2.1 42
Genetic Analysis 2.3 43
Experimental Insight 2.2 44
2.4 Probability Theory Predicts
Mendelian Ratios 44
The Product Rule 44
The Sum Rule 45
Conditional Probability 45
Binomial Probability 45
2.5 Chi-Square Analysis Tests the Fit
between Observed Values and
Expected Outcomes 47
The Normal Distribution 48
Chi-Square Analysis 48
Chi-Square Analysis of Mendel’s
Data 49
2.6 Autosomal Inheritance and Molecular
Genetics Parallel the Predictions of
Mendel’s Hereditary Principles 50
Autosomal Dominant Inheritance 51
Autosomal Recessive Inheritance 52
Molecular Genetics of Mendel’s Traits 53
Case Study Inheritance of Sickle Cell Disease
in Humans 55
Summary 56 ?? Keywords 57 ?? Problems 57
3 Cell Division and
Chromosome Heredity 63
3.1 Mitosis Divides Somatic Cells 64
Stages of the Cell Cycle 64
Substages of M Phase 65
Chromosome Distribution 68
Completion of Cell Division 70
Cell Cycle Checkpoints 71
Cell Cycle Mutations and Cancer 72
3.2 Meiosis Produces Gametes
for Sexual Reproduction 73
Meiosis versus Mitosis 73
Meiosis I 75
Meiosis II 79
The Mechanistic Basis of Mendelian Ratios 79
Segregation in Single-Celled Diploids 81
3.3 The Chromosome Theory of Heredity
Proposes That Genes Are Carried
on Chromosomes 81
Genetic Analysis 3.1 83
X-Linked Inheritance 84
Analysis of Nondisjunction 85
3.4 Sex Determination Is Chromosomal
and Genetic 87
Sex Determination in Drosophila 87
Mammalian Sex Determination 87
Genetic Analysis 3.2 88
Diversity of Sex Determination 89
3.5 Human Sex-Linked Transmission
Follows Distinct Patterns 90
Expression of X-Linked Recessive Traits 90
Experimental Insight 3.1 91
X-Linked Dominant Trait Transmission 93
Y-Linked Inheritance 94
Genetic Analysis 3.3 95
3.6 Dosage Compensation Equalizes
Dosage of Sex-Linked Genes 96
Random X-Chromosome Inactivation in
Placental Mammals 96
Case Study John Dalton’s Eyes Help Solve the Mystery
of Color Blindness 98
Summary 99 ?? Keywords 99 ?? Problems 100
4 Gene Interaction 105
4.1 Interactions between Alleles Produce
Dominance Relationships 106
The Molecular Basis of Dominance 106
Effects of Mutation 107
Incomplete Dominance 109
Codominance 110
Allelic Series 112
Genetic Analysis 4.1 113
Lethal Mutations 114
Sex-Limited Traits 117
Sex-Influenced Traits 118
Delayed Age of Onset 118
4.2 Some Genes Produce Variable
Phenotypes 119
Incomplete Penetrance 119
Variable Expressivity 119
Gene–Environment Interactions 120
Pleiotropic Genes 121
4.3 Gene Interaction Modifies Mendelian
Ratios 122
Gene Interaction in Pathways 123
The One Gene–One Enzyme Hypothesis 124
Experimental Insight 4.1 124
Genetic Dissection to Investigate
Gene Action 126
Epistasis and Its Results 127
Genetic Analysis 4.2 128
4.4 Complementation Analysis
Distinguishes Mutations in the Same
Gene from Mutations in Different
Genes 133
Genetic Analysis 4.3 134
Case Study Identification of Xeroderma Pigmentosum
Complementation Groups 136
Summary 136 ?? Keywords 137 ?? Problems 137
5 Genetic Linkage and
Mapping in Eukaryotes 143
5.1 Linked Genes Do Not Assort
Independently 144
Indications of Genetic Linkage 145
The Discovery of Genetic Linkage 147
Detecting Autosomal Genetic Linkage through
Test-Cross Analysis 149
Genetic Analysis 5.1 151
5.2 Genetic Linkage Mapping Is Based
on Recombination Frequency
between Genes 152
The First Genetic Linkage Map 152
Map Units 153
Chi-Square Analysis of Genetic Linkage
Data 153
5.3 Three-Point Test-Cross Analysis
Maps Genes 153
Finding the Relative Order of Genes
by Three-Point Mapping 153
Constructing a Three-Point Recombination
Map 155
Determining Gamete Frequencies from
Genetic Maps 158
5.4 Recombination Results from
Crossing Over 159
Cytological Evidence of Recombination 159
Limits of Recombination along
Chromosomes 159
Recombination within Genes 161
Biological Factors Affecting Accuracy of
Genetic Maps 161
Genetic Analysis 5.2 162
Correction of Genetic Map
Distances 163
5.5 Linked Human Genes Are Mapped
Using Lod Score Analysis 165
Allelic Phase 165
Lod Score Analysis 166
5.6 Genetic Linkage Analysis Traces
Genome Evolution 167
Experimental Insight 5.1 168
Genetic Analysis 5.3 169
5.7 Genetic Linkage in Haploid
Eukaryotes Is Identified by Tetrad
Analysis 170
Analysis of Unordered Tetrads 170
Ordered Ascus Analysis 173
5.8 Mitotic Crossover Produces
Distinctive Phenotypes 174
Case Study Mapping the Huntington Disease
Gene 176
Summary 177 ?? Keywords 178 ?? Problems 178
6 Genetic Analysis and
Mapping in Bacteria and
Bacteriophage 184
6.1 Bacteria Transfer Genes by
Conjugation 185
Characteristics of Bacterial Genomes 186
Conjugation Identified 186
Transfer of the F Factor 187
Formation of an Hfr Chromosome 189
Hfr Gene Transfer 191
6.2 Interrupted Mating Analysis Produces
Time-of-Entry Maps 193
Time-of-Entry Mapping Experiments 193
Consolidation of Hfr Maps 195
Genetic Analysis 6.1 196
6.3 Conjugation with F¿ Strains Produces
Partial Diploids 198
Genetic Analysis 6.2 200
6.4 Bacterial Transformation Produces
Genetic Recombination 201
Steps in Transformation 201
Mapping by Transformation 201
6.5 Bacterial Transduction Is Mediated
by Bacteriophages 203
Bacteriophage Life Cycles 203
Discovery of Transduction 205
Generalized Transduction 206
Cotransduction 207
Cotransduction Mapping 207
Specialized Transduction 209
6.6 Bacteriophage Chromosomes
Are Mapped by Fine-Structure
Analysis 209
Genetic Analysis 6.3 211
Genetic Complementation Analysis 212
Intragenic Recombination Analysis 212
Deletion Mapping Analysis 213
Case Study The Evolution of Antibiotic
Resistance 216
Summary 216 ?? Keywords 217 ?? Problems 218
12 Gene Mutation, DNA
Repair, and Homologous
Recombination 383
12.1 Mutations Are Rare and Occur
at Random 384
Mutation Frequency 384
The Fluctuation Test 386
12.2 Gene Mutations Modify DNA
Sequence 386
Base-Pair Substitution Mutations 387
Frameshift Mutations 388
Regulatory Mutations 389
Forward Mutation and Reversion 390
Genetic Analysis 12.1 391
12.3 Gene Mutations May Arise from
Spontaneous Events 392
DNA Replication Errors 392
Spontaneous Nucleotide Base Changes 392
DNA Nucleotide Lesions 395
12.4 Mutations May Be Induced by
Chemicals or Ionizing Radiation 395
Chemical Mutagens 396
Radiation-Induced DNA Damage 399
The Ames Test 400
12.5 Repair Systems Correct Some DNA
Damage 402
Direct Repair of DNA Damage 402
Genetic Analysis 12.2 403
Nucleotide Excision and Replacement 404
DNA Recombination Repair 405
DNA Damage Signaling Systems 406
DNA Damage Repair Disorders 407
12.6 Proteins Control Translesion DNA
Synthesis and the Repair of
Double-Strand Breaks 407
Translesion DNA Synthesis 407
Double-Strand Break Repair 408
12.7 Meiotic Recombination
Is Controlled by Programmed
Double-Strand Breaks 410
The Holliday Model 410
The Double-Stranded Break Model
of Meiotic Recombination 410
Holliday Junction Resolution 411
12.8 Gene Conversion Is Directed
Mismatch Repair in Heteroduplex
DNA 411
Case Study Li-Fraumeni Syndrome Is Caused
by Inheritance of Mutations of p53 415
Summary 416 ?? Keywords 417 ?? Problems 417
13 Chromosome Aberrations
and Transposition 422
13.1 Nondisjunction Leads to Changes
in Chromosome Number 423
Euploidy and Aneuploidy 423
Chromosome Nondisjunction 424
Gene Dosage Alteration 425
Aneuploidy in Humans 425
Reduced Fertility in Aneuploidy 427
Mosaicism 428
Uniparental Disomy 428
13.2 Changes in Euploidy Result in
Various Kinds of Polyploidy 429
Autopolyploidy and Allopolyploidy 429
Consequences of Polyploidy 430
Reduced Recessive Homozygosity 431
Polyploidy and Evolution 431
Genetic Analysis 13.1 432
13.3 Chromosome Breakage
Causes Mutation by Loss,
Gain, and Rearrangement of
Chromosomes 433
Partial Chromosome Deletion 433
Unequal Crossover 434
Detecting Duplication and Deletion 434
Deletion Mapping 436
13.4 Chromosome Breakage Leads to
Inversion and Translocation of
Chromosomes 436
Genetic Analysis 13.2 437
Chromosome Inversion 438
Chromosome Translocation 439
Experimental Insight 13.1 441
13.5 Transposable Genetic Elements
Move throughout the Genome 444
The Discovery of Transposition 444
Characteristics of Transposable Genetic
Elements 445
13.6 Transposition Modifies Bacterial
Genomes 445
Insertion Sequences 445
Genetic Analysis 13.3 447
Transposons 448
Transposition Mechanisms 448
13.7 Transposition Modifies Eukaryotic
Genomes 449
Drosophila P Elements 449
Retrotransposons 450
Case Study Human Chromosome Evolution 451
Summary 452 ?? Keywords 453 ?? Problems 454
16 Forward Genetics and
Recombinant DNA
Technology 522
16.1 Forward Genetic Screens
Identify Genes by Their Mutant
Phenotypes 523
Designing a Genetic Screen 524
Analysis of Mutageneses 528
Identifying Interacting and Redundant
Genes 528
Genetic Analysis 16.1 529
16.2 Specific DNA Sequences Are
Recognized Using Recombinant
DNA Technology 531
Restriction Enzymes 531
Experimental Insight 16.1 532
Genetic Analysis 16.2 534
Molecular Cloning 535
The Polymerase Chain Reaction 540
16.3 DNA Sequencing Technologies
Have Revolutionized Biology 542
Sequencing Long DNA Molecules 542
New Sequencing Technologies:
Next Generation and Third
Generation 542
16.4 Collections of Cloned DNA
Fragments Are Called
Libraries 543
Constructing Genomic Libraries 544
Constructing cDNA Libraries 545
Screening Libraries 545
16.5 Specific Genes Are Cloned
Using Recombinant DNA
Technology 546
Cloning Highly Expressed Genes 547
Cloning Homologous Genes 548
Cloning Genes by Complementation 549
Using Transposons to Clone Genes 550
Positional Cloning 550
Case Study Positional Cloning in Humans: The
Huntington Disease Gene 555
Summary 557 ?? Keywords 558 ?? Problems 558
18 Genomics: Genetics
from a Whole-Genome
Perspective 602
18.1 Structural Genomics Provides
a Catalog of Genes in
a Genome 603
The Clone-by-Clone Sequencing
Approach 603
Whole-Genome Shotgun Sequencing 604
The Human Genome 608
Metagenomics 608
Annotation to Describe Genes 608
Annotation to Describe Biological
Functions 609
Research Technique 18.1 610
Variation in Genome Organization among
Species 612
Three Insights from Genome
Sequences 614
18.2 Evolutionary Genomics Traces the
History of Genomes 614
The Tree of Life 614
Interspecific Genome Comparisons: Gene
Content 615
Research Technique 18.2 616
Interspecific Genome Comparisons: Genome
Annotation 620
Interspecific Genome Comparisons: Gene
Order 622
Intraspecific Genome Comparisons 623
Human Genetic Diversity 624
18.3 Functional Genomics Aids
in Elucidating Gene Function 627
Transcriptomics 627
Other “-Omes” and “-Omics” 630
Genomic Approaches to Reverse
Genetics 632
Use of Yeast Mutants to Categorize
Genes 632
Genetic Networks 633
Experimental Insight 18.1 634
Case Study Genomic Analysis of Insect Guts May
Fuel the World 636
Summary 636 ?? Keywords 637 ?? Problems 637
20 Developmental
Genetics 674
20.1 Development Is the Building
of a Multicellular Organism 675
Cell Differentiation 676
Pattern Formation 676
20.2 Drosophila Development
Is a Paradigm for Animal
Development 677
The Developmental Toolkit of
Drosophila 679
Maternal Effects on Pattern
Formation 679
Coordinate Gene Patterning of the
Anterior–Posterior Axis 681
Domains of Gap Gene Expression 682
Regulation of Pair-Rule Genes 683
Specification of Parasegments by
Hox Genes 684
Downstream Targets of Hox Genes 688
Hox Genes in Metazoans 688
Genetic Analysis 20.1 689
Stabilization of Cellular Memory by
Chromatin Architecture 690
Genetic Analysis 20.2 691
20.3 Cellular Interactions Specify
Cell Fate 692
Inductive Signaling between Cells 692
Lateral Inhibition 695
Cell Death during Development 695
20.4 “Evolution Behaves Like
a Tinkerer” 696
Evolution through Co-option 696
Constraints on Co-option 698
20.5 Plants Represent an Independent
Experiment in Multicellular
Evolution 698
Development at Meristems 698
Combinatorial Homeotic Activity
in Floral-Organ Identity 700
Case Study Cyclopia and Polydactyly—Different
Shh Mutations with Distinctive Phenotypes 702
Summary 704 ?? Keywords 704 ?? Problems 705
21 Genetic Analysis
of Quantitative Traits 708
21.1 Quantitative Traits Display
Continuous Phenotype
Variation 709
Genetic Potential 709
Major Genes and Additive Gene
Effects 710
Continuous Phenotypic Variation from
Multiple Additive Genes 711
Allele Segregation in Quantitative Trait
Production 713
Effects of Environmental Factors on
Phenotypic Variation 714
Genetic Analysis 21.1 715
Threshold Traits 716
Experimental Insight 21.1 717
21.2 Quantitative Trait Analysis Is
Statistical 718
Statistical Description of Phenotypic
Variation 719
Partitioning Phenotypic Variance 720
Partitioning Genetic Variance 721
21.3 Heritability Measures the Genetic
Component of Phenotypic
Variation 721
Genetic Analysis 21.2 722
Broad Sense Heritability 723
Twin Studies 723
Narrow Sense Heritability and Artificial
Selection 724
21.4 Quantitative Trait Loci Are the
Genes That Contribute to
Quantitative Traits 726
QTL Mapping Strategies 726
Identification of QTL Genes 729
Genome-Wide Association Studies 730
Case Study Artificial Selection for Oil and Protein
Content in Corn 732
Summary 733 ?? Keywords 733 ?? Problems 734
22 Population Genetics
and Evolution 737
22.1 The Hardy–Weinberg Equilibrium
Describes the Relationship of Allele
and Genotype Frequencies in
Populations 738
Populations and Gene Pools 738
The Hardy-Weinberg Equilibrium 739
Determining Autosomal Allele Frequencies
in Populations 740
The Hardy-Weinberg Equilibrium for More
than Two Alleles 742
Genetic Analysis 22.1 743
The Chi-Square Test of Hardy-Weinberg
Predictions 744
22.2 Genotype Frequencies for X-Linked
Genes Are Estimated Using the
Hardy-Weinberg Equilibrium 744
Determining Frequencies for X-Linked
Alleles 744
Hardy-Weinberg Equilibrium for X-Linked
Genes 746
22.3 Natural Selection Operates through
Differential Reproductive Fitness
within a Population 746
Differential Reproductive Fitness and Relative
Fitness 746
Directional Natural Selection 747
Natural Selection Favoring Heterozygotes 749
22.4 Mutation Diversifies Gene
Pools 750
Effects of Forward and Reverse Mutation
Rates 750
Mutation–Selection Balance 750
22.5 Migration Identifies Movement
of Organisms and Genes between
Populations 751
Effects of Gene Flow 751
Allele Frequency Equilibrium and
Equalization 752
22.6 Genetic Drift Causes Allele
Frequency Change by Sampling
Error 752
The Founder Effect 753
Genetic Bottlenecks 754
22.7 Nonrandom Mating Alters
Genotype Frequencies 754
The Coefficient of Inbreeding 755
Inbreeding Depression 756
Genetic Analysis 22.2 757
Effects of Assortative Mating 757
22.8 Species and Higher Taxonomic
Groups Evolve by the Interplay
of Four Evolutionary Processes 758
Processes of Speciation 758
Reproductive Isolation and
Speciation 759
Case Study CODIS—Using Population Genetics to
Solve Crime and Identify Paternity 761
Summary 763 ?? Keywords 764 ?? Problems 764
Selected References and Readings R-1
Answers to Selected Problems A-1
Glossary G-1
Credits C-1
Index I-1