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1 FIFTH EDITION IV I ^HHk ^ttm IZTI/^Q i I II MPHBBMWBBIHB '-llwmpbi^hbwm^^pfc ' GSBHSRSBRSRRk LlML I I \l 1MB ^HP'^^MMMP" jflp^^^^^^^^st I Iv^O FROM GENES TO GENOMES %^MiM^PM^^MWi99Mi$9i0^^ ^^^^^^^^^^^^^V^^^fii^^t^i^^^^^ ^^^Ifi^6lt#:*s4^ i ill! BQPIP *mt&-wti itip31 "it* la ^^^^J*^ Hi ^^^H*" Slll«PB «#iii<ib»wp«%iiiiii Mi "til illt LELANDH. li4»twlil MICHAEL L. goidbkc %itll

2 1 Genetics: The Study of Biological Information 1 Basic Principles: How Traits Are Transmitted 14 2 Mendel's Principles of Heredity 14 3 Extensions to Mendel's Laws 45 4 The Chromosome Theory of Inheritance 85 5 Linkage, Recombination, and the Mapping of How Genes Travel on Chromosomes The Eukaryotic Chromosome Chromosomal Rearrangements and Changes in Chromosome Number Bacterial Genetics Organellar Inheritance 491 Genes on Chromosomes 127 How Genes Are Regulated 514 What Genes Are and What They Do Gene Regulation in Prokaryotes Gene Regulation in Eukaryotes DNA Structure, Replication, and Recombination Anatomy and Function of a Gene: Dissection Through Mutation Gene Expression: The Flow of Information from DNA to RNA to Protein 254 Using Genetics Manipulating the Genomes of Eukaryotes The Genetic Analysis of Development The Genetics of Cancer 631 Analysis of Genetic Information Digital Analysis of Genomes Analyzing Genomic Information 342 Beyond the Individual Gene and Genome Variation and Selection in Populations Genetics of Complex Traits 694

3 About The Authors iii Preface x Acknowledgements xxv Introduction: Genetics in the Twenty-First Century 1 chapter 1 Genetics: The Study of Biological Information DNA:The Fundamental Information Molecule of Life Proteins: The Functional Molecules of Life Processes Molecular Similarities of All Life-Forms The Modular Construction of Genomes Modern Genetic Techniques Human Genetics and Society Extensions to Mendel for Multifactorial chapter 4 Inheritance 55 Genetics and Society: Disease Prevention Versus the Right to Privacy 71 The Chromosome Theory of Inheritance Chromosomes: The Carriers of Genes Sex Chromosomes and Sex Determination Mitosis: Cell Division That Preserves Chromosome Number Meiosis: Cell Divisions That Halve Chromosome Number Gametogenesis Validation of the Chromosome Theory Sex-Linked and Sexually Dimorphic Traits in Humans 114 Genetics and Society: Prenatal Genetic Diagnosis 89 Fast Forward: Transgenic Mice Prove That SPY Is the Maleness Factor 93 chapter 5 Linkage, Recombination, and the Mapping of Genes on Chromosomes 127 chapter 2 Mendel's Principles of Heredity Background:The Historical Puzzle of Inheritance Genetic Analysis According to Mendel Mendelian Inheritance in Humans 30 Genetics and Society: Developing Guidelines for Genetic Screening 34 chapter 3 Extensions to Mendel's Laws Extensions to Mendel for Single-Gene Inheritance Gene Linkage and Recombination Recombination: A Result of Crossing-Over During Meiosis Mapping: Locating Genes Along a Chromosome The Chi-Square Test and Linkage Analysis Tetrad Analysis in Fungi Mitotic Recombination and Genetic Mosaics 157 Fast Forward: Gene Mapping May Cystic Fibrosis 143 Tools of Genetics: The Chi-Square Test for Goodness of Fit 147 Lead to a Cure for Genetics and Society: Mitotic Recombination and Cancer Formation 159 vi

4 Contents vii What Genes Are and What They Do 173 Analysis of Genetic Information 298 chapter 6 DNA Structure, Replication, and Recombination Experimental Evidence for DNA as the Genetic Material The Watson and Crick Double Helix Model of DNA Genetic Information in Nucleotide Sequence DNA Replication Recombination at the DNA Level 193 chapter 9 Digital Analysis of Genomes Fragmenting DNA Cloning DNA Fragments Sequencing DNA Sequencing Genomes Finding the Genes in Genomes Genome Architecture and Evolution Bioinformatics: Information Technology and Genomes A Comprehensive Example: The Hemoglobin Genes 329 chapter 7 Anatomy and Function of a Gene: Dissection Through Mutation Mutations: Primary Tools of Genetic Analysis Molecular Mechanisms of Mutation 7.3 What Mutations Tell Us About Gene Structure What Mutations Tell Us About Gene Function A Comprehensive Example; Mutations That Affect Vision 241 «Fast Forward: Trinucleotide Repeat Diseases: 212 Huntington Disease and Fragile X Syndrome 216 Tools of Genetics: Serendipity in Science: The Discovery of Restriction Enzymes 301 chapter 10 Analyzing Genomic Information Variation Among Genomes Genotyping a Known Disease-Causing Mutation 347 Sampling DNA Variation in a Genome 353 Positional Cloning 357 The Era of Whole-Genome Sequencing 363 Tools of Genetics: The Lod Score Statistic 361 chapter 8 Gene Expression: The Flow of Information from DNA to RNA to Protein The Genetic Code 255 Transcription: From DNA to RNA 264 Translation: From mrna to Protein 273 How Genes Travel on Chromosomes Differences in Gene Expression Between Prokaryotes and Eukaryotes 281 The Effects of Mutations on Gene Expression and Function 283 Genetics and Society: HIV and Reverse Transcription 268 chapter 11 The Eukaryotic Chromosome Chromosomal DNA and Proteins Chromosome Structure and Compaction 383

5 viii Contents 11.3 Chromosomal Packaging and Gene Expression Replication of Eukaryotic Chromosomes Chromosome Segregation Artificial Chromosomes 401 chapter 12 Chromosomal Rearrangements and Changes in Chromosome Number Rearrangements of Chromosomal DNA The Effects of Rearrangements Transposable Genetic Elements Aberrations in Chromosome Number: Aneuploidy Variation in Number of Chromosome Sets: Euploidy Genome Restructuring and Evolution 443 Fast Forward: Programmed DNA Rearrangements and the Immune System 412 chapter 15 Gene Regulation in Prokaryotes The Elements of Prokaryotic Gene Expression Regulation of Transcription Initiation via DNA-Binding Proteins RNA-Mediated Mechanisms of Gene Regulation Discovering and Manipulating Bacterial Gene Regulatory Mechanisms A Comprehensive Example: Control of Bioiuminescence by Quorum Sensing 537 chapter 13 Bacterial Genetics The Enormous Diversity of Bacteria Bacterial Genomes Bacteria as Experimental Organisms Gene Transfer in Bacteria Bacterial Genetic Analysis A Comprehensive Example: How N. gonorrhoeae Became Resistant to Penicillin 481 chapter 16 Gene Regulation in Eukaryotes Overview of Eukaryotic Gene Regulation Control of Transcription Initiation Through Enhancers Epigenetics: Control of Transcription Initiation Through DNA Methylation Regulation After Transcription A Comprehensive Example: Sex Determination in Drosophila 564 chapter 14 Organellar Inheritance Mitochondria and Their Genomes Chloroplasts and Their Genomes The Relationship Between Organellar and Nuclear Genomes Non-Mendelian Inheritance of Mitochondria and Chloroplasts Mutant Mitochondria and Human Disease 505 Genetics and Society: Mitochondrial DNA Tests as Evidence of Kinship in Argentine Courts 502 chapter 17 Manipulating Eukaryotes 575 the Genomes of 17.1 Creating Transgenic Organisms Uses oftransgenic Organisms 579

6 Contents 17.3 Targeted Mutagenesis Human Gene Therapy 590 Tools of Genetics: Cloning by Somatic Cell Nuclear Transfer 582 chapter 18 The Genetic Analysis of Development Model Organisms: Prototypes for Developmental Genetics Mutagenesis Screens Determining Where and When Genes Act Ordering Genes in a Pathway A Comprehensive Example: Body Plan Development in Drosophila 610 chapter20 Variation and Selection in Populations The Hardy-Weinberg Law: Predicting Genetic Variation in "Ideal" Populations What Causes Allele Frequencies to Change in Real Populations? Ancestry and the Evolution of Modern Humans 680 chapter 19 The Genetics of Cancer Characteristics of Cancer Cells The Genetic Basis of Cancers How Cell Division Is Normally Controlled 637 chapter 21 Genetics of Complex Traits Heritability: Genetic Versus Environmental Influences on Complex Traits Mapping Quantitative Trait Loci (QTLs) How Mutations Cause Cancer Phenotypes Personalized Cancer Treatment 649 Tools of Genetics: Analysis ofcell-cycle Mutants in Yeast 640 Guidelines for Gene Nomenclature Brief Answer Section B1 Glossary G1 Credits C Index II A1

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