Human genetics : concepts and applications / Ricki Lewis

Includes glossary and index

Contents
About the Author iii
List of Boxes vi
Clinical Coverage vii
Preface xii
Visual Preview xvi
PART ONE
Introduction 1
Chapter 1
Overview of Genetics 1
1.1 Genetic Testing 2
1.2 The Breadth of Genetics 4
DNA 4
Genes, Chromosomes, and Genomes 6
Cells, Tissues, and Organs 6
Individual 6
Family 6
Population 7
Evolution 7
1.3 Genes Do Not Usually Function Alone 9
1.4 Geneticists Use Statistics to Represent Risks 10
1.5 Applications of Genetics 10
Establishing Identity and Origins 11
Health Care 13
Agriculture 15
Genetics from a Global Perspective 16
Chapter 2
Cells 21
2.1 The Components of Cells 22
Chemical Constituents of Cells 23
Organelles 23
The Plasma Membrane 28
The Cytoskeleton 30
2.2 Cell Division and Death 33
The Cell Cycle 34
Apoptosis 35
2.3 Cell-Cell Interactions 38
Signal Transduction 38
Cellular Adhesion 38
2.4 Stem Cells and Cell Specialization 39
Cell Lineages 39
Stem Cell Technology Using Embryos 40
Stem Cell Technology Using Cells from Adults 40
Chapter 3
Development 47
3.1 The Reproductive System 48
The Male 48
The Female 48
3.2 Meiosis 49
3.3 Gamete Maturation 53
Sperm Development 53
Oocyte Development 54
3.4 Prenatal Development 56
Fertilization 56
Early Events-Cleavage and Implantation 56
The Embryo Forms 58
Supportive Structures 59
Multiples 60
The Embryo Develops 62
The Fetus 63
3.5 Birth Defects 64
The Critical Period 64
Teratogens 64
3.6 Maturation and Aging 66
Adult-Onset Inherited Disorders 67
Accelerated Aging Disorders 67
Is Longevity Inherited? 69
PART TWO
Transmission
Genetics 73
Chapter 4
Mendelian Inheritance 73
4.1 Following the Inheritance of One Gene-Segregation 74
Mendel the Man 74
Mendel's Experiments 74
Terms and Tools to Follow Segregating Genes 76
4.2 Single-Gene Inheritance in Humans 78
Modes of Inheritance 78
Solving a Problem: Segregation 83
On the Meaning of Dominance and Recessiveness 83
4.3 Following the Inheritance of Two Genes Independent
Assortment 84
Mendel's Second Law 84
Solving a Problem: Following More Than One Segregating Gene 85
4.4 Pedigree Analysis 86
Pedigrees Then and Now 86
Pedigrees Display Mendel's Laws 87
Solving a Problem: Conditional Probability 88
Chapter 5
Extensions and Exceptions to Mendel's Laws 93
5.1 When Gene Expression Appears to Alter Mendelian Ratios 94
Lethal Allele Combinations 94
Multiple Alleles 94
Different Dominance Relationships 95
Epistasis-When One Gene Affects Expression of Another 96
Penetrance and Expressivity 97
Pleiotropy-One Gene, Many Effects 97
Phenocopies-When It's Not in the Genes 98
Genetic Heterogeneity-More than One Way to Inherit a Trait 98
The Human Genome Sequence Adds Perspective 98
5.2 Maternal Inheritance and Mitochondrial Genes 100
Mitochondrial Disorders 101
Heteroplasmy Complicates Mitochondrial Inheritance 102
Mitochondrial DNA Studies Clarify the Past 102
5.3 Linkage 102
Linkage Was Discovered in Pea Plants 102
Linkage Maps 103
Solving a Problem: Linked Genes in Humans 105
The Evolution of Gene Mapping 106
Chapter 6
Matters of Sex 111
6.1 Sexual Development 112
Sex Chromosomes 112
The Phenotype Forms 113
Is Homosexuality Inherited? 116
6.2 Traits Inherited on Sex Chromosomes 118
X-Linked Recessive Inheritance 119
X-Linked Dominant Inheritance 120
Solving a Problem: X-Linked Inheritance 123
6.3 X Inactivation Equalizes the Sexes 124
6.4 Sex-Limited and Sex-Influenced Traits 126
Sex-Limited Traits 126
Sex-Influenced Traits 127
6.5 Genomic Imprinting 127
Silencing the Contribution from One Parent 127
Imprinting Disorders in Humans 128
A Sheep With a Giant Rear End 128
Chapter 7
Multifactorial Traits 133
7.1 Genes and the Environment Mold Most Traits 134
Polygenic Traits Are Continuously Varying 135
Fingerprint Patterns 135
Height 135
Eye Color 136
A Closer Look at Skin Color 136
7.2 Methods Used to Investigate Multifactorial Traits 138
Empiric Risk 138
Heritability-The Genetic Contribution to a Multifactorial Trait 140
Adopted Individuals 141
Twins 141
Association Studies 143
7.3 Some Multifactorial Traits 145
Heart Health 145
Body Weight 146
Chapter 8
The Genetics of Behavior 153
8.1 Genes Contribute to Most Behavioral Traits 154
8.2 Eating Disorders 155
8.3 Sleep 157
Narcolepsy 157
Familial Advanced Sleep Phase Syndrome 158
8.4 Intelligence 158
8.5 Drug Addiction 160
8.6 Mood Disorders 161
8.7 Schizophrenia 163
PART THREE
DNA and Chromosomes 167
Chapter 9
DNA Structure and Replication 167
9.1 Experiments Identify
and Describe the Genetic Material 168
DNA Is the Hereditary Molecule 168
DNA Is the Hereditary Molecule-and Protein Is Not 168
Deciphering the Structure of DNA 169
9.2 DNA Structure 172
9.3 DNA Replication-Maintaining Genetic Information 177
Replication Is Semiconservative 177
Steps and Participants in DNA Replication 178
9.4 PCR-Directing DNA Replication 180
Chapter 10
Gene Action:
From DNA to Protein 185
10.1 Transcription-The Link Between Gene and Protein 186
RNA Structure and Types 186
Transcription Factors 188
Steps of Transcription 189
RNA Processing 189
10.2 Translation of a Protein 191
Deciphering the Genetic Code 191
Building a Protein 194
10.3 Protein Folding 197
Chapter 11
Control of Gene Expression 203
11.1 Gene Expression Through Time and Tissue 204
Globin Chain Switching 204
Building Tissues and Organs 205
Proteomics 206
11.2 Mechanisms of Gene Expression 207
The Histone Code 207
RNA Interference 208
11.3 Proteins Outnumber Genes 209
11.4 The "Other" 98.5 Percent of the Human Genome 211
Noncoding (nc) RNAs 211
Repeats 212
Chapter 12
Gene Mutation 215
12.1 Mutations Can Alter Proteins-Three Examples 216
The Beta Globin Gene 216
Disorders of Orderly Collagen 217
A Mutation That Causes Early-Onset Alzheimer Disease 219
Multiple Mutations and Confusion 220
12.2 Causes of Mutation 220
Spontaneous Mutation 220
Induced Mutations 222
Natural Exposure to Mutagens 223
12.3 Types of Mutations 224
Point Mutations 224
Splice Site Mutations 226
Deletions and Insertions Can Cause Frameshifts 226
Pseudogenes and Transposons Revisited 228
Expanding Repeats Lead to Protein Misfolding 228
12.4 The Importance of a Mutation's Position in the Gene 231
Globin Variants 231
Inherited Susceptibility to Prion Disorders 232
12.5 Factors That Lessen the Effects of Mutation 232
12.6 DNA Repair 233
Types of DNA Repair 233
DNA Repair Disorders 234
Chapter 13
Chromosomes 239
13.1 Portrait of a Chromosome 240
Telomeres and Centromeres Are Essential 240
Karyotypes Are Chromosome Charts 242
13.2 Visualizing Chromosomes 244
Obtaining Cells for Chromosome Study 244
Preparing Cells for Chromosome Observation 246
13.3 Abnormal Chromosome Number 249
Polyploidy 250
Aneuploidy 250
13.4 Abnormal Chromosome Structure 255
Deletions and Duplications 256
Translocations 257
Inversions 259
Isochromosomes and Ring Chromosomes 260
13.5 Uniparental Disomy-Two Genetic Contributions from One Parent 262
PART FOUR
Population
Genetics 267
Chapter 14
When Allele Frequencies Stay Constant 267
14.1 The Importance of Knowing Allele Frequencies 268
14.2 When Allele Frequencies Stay Constant 268
Hardy-Weinberg Equilibrium 268
Solving a Problem: The Hardy-Weinberg Equation 269
14.3 Practical Applications of Hardy-Weinberg Equilibrium 270
14.4 DNA Profiling-A Practical Test of Hardy-Weinberg Assumptions 272
DNA Patterns Distinguish Individuals 272
Population Statistics Are Used to Interpret DNA Profiles 273
DNA Profiling to Identify World Trade Center Victims 276
Chapter 15
Changing Allele Frequencies 281
15.1 Nonrandom Mating 282
15.2 Migration 283
Historical Clues 283
Geographical and Linguistic Clues 284
15.3 Genetic Drift 284
The Founder Effect 284
Population Bottlenecks 287
15.4 Mutation 288
15.5 Natural Selection 288
Tuberculosis Ups and Downs-and Ups 289
Evolving HIV 290
Balanced Polymorphism 291
15.6 Gene Genealogy 296
PKU Revisited 297
CF Revisited 298
Chapter 16
Human Origins
and Evolution 303
16.1 Human Origins 304
The Australopithecines-and Others? 305
Homo 306
Modern Humans 308
16.2 Molecular Evolution 309
Comparing Genes and Genomes 310
Solving a Problem: Comparing Chimps and Humans 311
Comparing Chromosomes 313
Comparing Protein Sequences 314
16.3 Molecular Clocks 318
Neanderthals Revisited 318
Tracking the Sexes: mtDNA and the Y Chromosome 319
16.4 Eugenics 321
PART FIVE
Immunity and Cancer 329
Chapter 17
Genetics of Immunity 329
17.1 The Importance of Cell Surfaces 330
Pathogens 330
Genetic Control of Immunity 330
Blood Groups 331
The Human Leukocyte Antigens 332
17.2 The Human Immune System 334
Physical Barriers and the Innate Immune Response 334
The Adaptive Immune Response 335
17.3 Abnormal Immunity 339
Inherited Immune Deficiencies 339
Acquired Immune Deficiency Syndrome 339
Autoimmunity 340
Allergies 342
17.4 Altering Immune Function 343
Vaccines 343
Immunotherapy 344
Transplantation 346
17.5 A Genomic View of Immunity-The Pathogen's Perspective 348
Crowd Diseases 348
Bioweapons 348
Chapter 18
The Genetics of Cancer 353
18.1 Cancer as a Genetic Disorder 354
From Single Mutations to Sweeping Changes in Gene Expression 354
Loss of Cell Cycle Control 354
Inherited Versus Sporadic Cancer 355
18.2 Characteristics of Cancer Cells 357
18.3 Genes That Cause Cancer 359
Oncogenes 359
Tumor Suppressors 361
18.4 A Series of Genetic Changes Causes Some Cancers 365
A Rapidly Growing Brain Tumor 365
Colon Cancer 365
18.5 Cancer Prevention, Diagnosis, and Treatment 367
Investigating Environmental Causes of Cancer 367
Diagnosing and Treating Cancer 368
PART SIX
Genetic Technology 373
Chapter 19
Genetically Modified Organisms 373
19.1 Of Pigs and Patents 374
19.2 Recombinant DNA Technology 375
Constructing Recombinant DNA Molecules-An Overview 376
Isolating the Gene of Interest 377
Selecting Recombinant DNA Molecules 378
Delivering DNA in Plants and Animals 379
19.3 Applications of Recombinant DNA Technology 381
Drugs 381
Textiles 382
Paper and Wood Products 382
Food 383
Bioremediation 384
19.4 Gene Targeting 385
Gene-Targeted Mice as Models 385
When Knockouts Are Normal 386
19.5 Antisense Technology 387
Chapter 20
Gene Therapy and Genetic Counseling 391
20.1 Gene Therapy Successes and Setbacks 392
Adenosine Deaminase Deficiency-Early Success 392
Ornithine Transcarbamylase Deficiency-A Setback 393
A Success in the Making-Canavan Disease 395
20.2 The Mechanics of Gene Therapy 396
Treating the Phenotype 397
Germline Versus Somatic Gene Therapy 397
Sites of Somatic Gene Therapy 398
Gene Delivery 401
20.3 A Closer Look: Treating Sickle Cell Disease 402
20.4 Genetic Screening and Genetic Counseling 403
Genetic Counselors Provide Diverse Services 403
Scene from a Sickle Cell Disease Clinic 404
Genetic Counseling Quandaries and Challenges 404
Perspective: A Slow Start, New Complications, But Great Promise 405
Chapter 21
Reproductive Technologies 409
21.1 Infertility and Subfertility 410
Male Infertility 410
Female Infertility 411
Infertility Tests 413
21.2 Assisted Reproductive Technologies 413
Donated Sperm-Intrauterine Insemination 413
A Donated Uterus-Surrogate Motherhood 413
In Vitro Fertilization 415
Gamete Intrafallopian Transfer 415
Oocyte Banking and Donation 416
Preimplantation Genetic Screening and Diagnosis 417
21.3 On the Subject of "Spares" 419
Chapter 22
The Age of Genomics 425
22.1 Genome Sequencing: A Continuation of Genetics 426
22.2 The Origin of the Idea 428
The Sanger Method of DNA Sequencing 428
The Project Starts 430
22.3 Technology Drives the Sequencing Effort 431
22.4 Into the Future 433
A Multilevel House 433
New Types of Studies 436
Epilogue: Genome Information Will Affect You 436
Answers to End-of-Chapter Questions A-1
Glossary G-1
Credits C-1
Index I-1