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The human genome / by Julia E. Richards, R. Scott Hawley. — 3rd ed. — Amsterdam : Elsevier, c2011. – (59.34/R516/3rd ed.) |
Contents
Contents
Acknowledgments xi
Prologue: The Answer in a Nutshell xiii
I HOW GENES SPECIFY A TRAIT
1 The Basics of Heredity: How Traits Are Passed Along in Families 3
1.1 Mendel's Laws 4
1.2 Selection: Artificial， Natural， and Sexual 12
1.3 Human Genetic Diversity 15
1.4 Human Dominant Inheritance 16
1.5 Human Recessive Inheritance 19
1.6 Complementation 27
1.7 Epistasis and Pleiotropy 31
1.8 Complex Syndromes 32
1.9 One Man's Disease Is Another Man's Trait
2 The Double Helix: How Cells Preserve Genetic Information 41
2.1 Inside the Cell 42
2.2 DNA: The Repository of Genetic Information 44
2.3 DNA and the Double Helix 47
2.4 DNA Replication 50
2.5 Chromatin 56
2.6 What Are Chromosomes? 57
2.7 Euchromatin and Heterochromatin 64
2.8 The Mitochondrial Chromosome: The "Other Genome" in the Human Genome 65
2.9 DNA in vitro 67
II HOW GENES FUNCTION
3 The Central Dogma of Molecular Biology: How Cells Orchestrate the Use of Genetic Information 83
3.1 What Is RNA? 84
3.2 What Is RNA For? 87
3.3 Transcription of RNA 89
3.4 Orchestrating Expression 91
3.5 Monitoring Gene Expression 95
3.6 Interaction of Transcription Factors 98
3.7 Inducible Genes 102
3.8 Epigenetic Control of Gene Expression 104
3.9 What Constitutes Normal? 106
4 The Genetic Code: How the Cell Makes Proteins from Genetic Information Encoded in mRNA Molecules 115
4.1 The Genetic Code 116
4.2 Moving Things In and Out of the Nucleus 119
4.3 The Central Dogma of Molecular Biology 120
4.4 Translation 120
4.5 Messenger RNA Structure 122
4.6 Splicing 124
4.7 Modular Genes 128
4.8 What Are Proteins? 130
4.9 Gene Products and Development 135
5 We Are All Mutants: How Mutation Alters Function 143
5.1 What Is a Mutation? 144
5.2 The Process of Mutation 147
5.3 How We Detect Mutations 153
5.4 Basic Mutations 159
5.5 Mutations in DNA Sequences that Regulate Gene Expression 166
5.6 Copy Number Variation: Too Much or Too Little of a Good Thing 167
5.7 Expanded Repeat Traits 169
5.8 The Male Biological Clock 180
5.9 Mutation Target Size 180
5.10 Absent Essentials and Monkey Wrenches 183
III HOW CHROMOSOMES MOVE
6 Mitosis and Meiosis: How Cells Move Your Genes Around 199
6.1 The Cell Cycle 200
6.2 Mitosis 201
6.3 Gametogenesis: What Is Meiosis Trying to Accomplish? 207
6.4 Meiosis in Detail 211
6.5 Mechanisms of Chromosome Pairing in Meiosis 217
6.6 The Chromosomal Basis of Heredity 219
6.7 Aneuploidy: When Too Much or Too Little Counts 224
6.8 Uniparental Disomy 230
6.9 Partial Aneuploidies 236
6.10 The Female Biological Clock 238
Appendix 6.1 Failed Meiotic Segregation (Nondisjunction) as Proof of the Chromosome Theory of Heredity 240
7 The Odd Couple: How the X and Y Chromosomes Break the Rules 247
7.1 Passing the X and Y Chromosomes between Generations 248
7.2 How Humans Cope with the Difference in Number of Sex Chromosomes between Males and Females 249
7.3 How X Inactivation Works 250
7.4 Skewed X Inactivation - When Most Cells Inactivate the Same X 251
7.5 Genes that Escape X-Inactivation 255
7.6 Reactivation of the Inactive X Chromosome in the Female Germline 255
7.7 X Chromosome Inactivation During Male Meiosis 255
7.8 X Inactivation and the Phenotypes of Sex Chromosome Aneuploidy 257
7.9 The Structure of the Human Y Chromosome 259
7.10 X-Linked Recessive Inheritance 262
7.11 X-Linked Dominant Inheritance 265
IV HOW GENES CONTRIBUTE TO COMPLEX TRAITS
8 Sex Determination: How Genes Determine a Developmental Choice 273
8.1 Sex as a Complex Developmental Characteristic 274
8.2 What Do the X and Y Chromosomes Have to Do With Sex? 278
8.3 SRY on the Y: The Genetic Determinant of Male Sexual Differentiation 279
8.4 The Role of Hormones in Early Development 282
8.5 Androgen Receptor on the X: Another Step in the Sexual Differentiation Pathway
8.6 Genetics of Gender Identification 287
8.7 Genetics of Sexual Orientation 288
9 Complexity: How Traits Can Result from Combinations of Factors 299
9.1 Digenic Diallelic Inheritance 300
9.2 Digenic Triallelic Inheritance 304
9.3 Multifactorial Inheritance 305
9.4 Quantitative Traits 307
9.5 Additive Effects and Thresholds 309
9.6 Is It Genetic? 310
9.7 Genes and Environment: Inducible Traits 312
9.8 Genes and Environment: Infectious Disease 315
9.9 Phenocopies 319
9.10 Genotypic Compatibility: Whose Genome Matters? 322
9.11 Phenotypic Heterogeneity: One Gene， Many Traits 324
9.12 Genotypic and Phenotypic Heterogeneity 325
9.13 Variable Expressivity 328
9.14 Phenotypic Modifiers 329
9.15 Biochemical Pathways Underlying Complexity 331
9.16 Behavioral Genetics 334
9.17 Genes Expression: Another Level of Complexity 337
10 The Multiple-Hit Hypothesis: How Genes Play a Role in Cancer 343
10.1 The War on Cancer 344
10.2 Cancer as a Defect in Regulation of the Cell Cycle 345
10.3 Cancer as a Genetic Disease 346
10.4 Cancer and the Environment 348
10.5 Tumor Suppressor Genes and the Two-Hit Hypothesis 348
10.6 Cell-Type Specificity of Tumor Suppressor Gene Defects 352
10.7 The Multi-Hit Hypothesis 353
10.8 The Activation of Proto-Oncogenes and the Role of Oncogenes in Promoting Cancer
10.9 Defects in DNA Repair 357
10.10 Personalized Medicine 358
10.11 Cancer Biomarkers 361
V HOW GENES ARE FOUND
11 The Gene Hunt: How Genetic Maps Are Built and Used 369
11.1 What Is a Genetic Map? 370
11.2 What Is a Genetic Marker? 372
11.3 Finding Genes before There Were Maps 378
11.4 Defining the Thing to Be Mapped 380
11.5 Recombination as a Measure of Genetic Distance 382
11.6 Physical Maps and Physical Distances 388
11.7 How Did They Build Genetic Maps? 393
11.8 After the Map: What Came Next? 396
12 The Human Genome: How the Sequence Enables Genome-wide Studies 405
12.1 The Human Genome Project 406
12.2 The Human Genorae Sequence 416
12.3 The Other Genome Projects 418
12.4 The Genes in the Human Genome 420
12.5 Human Genome Variation 428
12.6 Genome-wide Technologies 432
12.7 Genome-wide Association 433
12.8 Allele Sharing and Sib Pair Analysis 439
12.9 Copy Number Variation and Gene Dosage 440
12.10 Whole Genome Sequencing 443
VI HOW GENES PLAY A ROLE IN TESTING AND TREATMENT
13 Genetic Testing and Screening: How Genotyping Can Offer Important Insights 455
13.1 What Is Medical Genetics? 457
13.2 Screening vs. Testing 459
13.3 Preimplantation Genetic Screening 461
13.4 Prenatal Diagnosis During the First Trimester 463
13.5 Prenatal Diagnosis During the Second Trimester 465
13.6 Amniocentesis and Chorionic Villus Sampling 466
13.7 Analysis of Fetal Cells 469
13.8 Sex Selection 473
13.9 Newborn Screening 474
13.10 Adult Genetic Screening and Testing 475
13.11 Ethical， Legal， and Social Issues 480
14 Magic Bullets: How Gene-based Therapies Personalize Medicine 487
14.1 Replacing a Lost Gene or Funtion - The RPE65 Story 488
14.2 Replacing a Lost Gene - ADA Deficiency 492
14.3 Targeting Downstream Disease Pathology 493
14.4 Suppressing the Unwanted Genotype - Use of siRNAs and miRNAs 495
14.5 Gene Supplement Therapy- More of the Same 497
14.6 Strategies for Cancer Therapy 498
14.7 Gene-based Therapy Instead of Gene Therapy 500
14.8 Delivering Gene Therapy 502
14.9 Do We Have to Treat the Whole Body? 503
14.10 What Are the Biggest Problems with Gene Therapy? 505
14.11 So， Whom Do We Treat? 506
15 Fears， Faith， and Fantasies: How the Past and Present Shape the Future of Genomic Medicine 513
15.1 Fears - A Tale of Eugenics 514
15.2 Faith - A Tale of Ethical， Legal， and Social Advances 518
15.3 Fantasies- A Tale of Our Genetic Future 522
Answers to Study Questions 527
Glossary 553
Index 575
