and Evolution 305 16.1 Human Origins 306 Hominoids and Hominids 306 Australopithecus 306 Homo 308 Modern Humans 310 16.2 Molecular Evolution 311 Comparing Genes and Genomes 311 Comparing Chimps and Humans 312 Comparing Chromosomes 316 Comparing Proteins 317 16.3 Molecular Clocks 319 Neanderthals Revisited 319 Tracking the Sexes: mtDNA and the Y Chromosome 320 The African Slave Trade 321 Native American Origins 322 16.4 Eugenics 322 PART FIVE Immunity and Cancer 331 Chapter 17 Genetics of Immunity 331 17.1 The Importance of Cell Surfaces 332 Pathogens 332 Genetic Control of Immunity 333 Blood Groups 333 The Human Leukocyte Antigens 335 17.2 The Human Immune System 336 Physical Barriers and the Innate Immune Response 336 The Adaptive Immune Response 338 17.3 Abnormal Immunity 341 Inherited Immune Deficiencies 341 Acquired Immune Deficiency Syndrome 342 Autoimmunity 343 Allergies 344 17.4 Altering Immune Function 345 Vaccines 345 Immunotherapy 346 Transplants 348 17.5 A Genomic View of Immunity?The Pathogen?s Perspective 350 Crowd Diseases 350 Bioweapons 351 Chapter 18 The Genetics of Cancer 355 18.1 Cancer Is Genetic, But Usually Not Inherited 356 From Single Mutations to Sweeping Changes in Gene Expression 356 Loss of Cell Cycle Control 357 Inherited Versus Sporadic Cancer 357 18.2 Characteristics of Cancer Cells 359 18.3 Origins of Cancer Cells 361 18.4 Genes Associated with Cancer 363 Oncogenes 363 Tumor Suppressors 365 18.5 A Series of Genetic Changes Causes Some Cancers 370 A Rapidly Growing Brain Tumor 370 Colon Cancer 370 18.6 Environmental Causes of Cancer 371 Considering Carcinogens 372 18.7 Human Genome Data Tailor Diagnosis and Treatment 373 PART SIX Genetic Technologies 377 Chapter 19 Genetic Technologies: Amplifying, Modifying, and Monitoring DNA 377 19.1 Patenting DNA 378 19.2 Amplifying DNA 379 19.3 Modifying DNA 380 Recombinant DNA Technology and Transgenic Organisms 381 Gene Targeting 389 19.4 Monitoring Gene Function 390 Gene Expression Microarrays Track the Aftermath of Spinal Cord Injury 390 Solving a Problem: Interpreting a DNA Sequence Variation Microarray 392 Chapter 20 Genetic Testing, Genetic Counseling, and Gene Therapy 397 20.1 Genetic Testing and Counseling 398 Genetic Testing 398 Genetic Counseling 399 Genetic Privacy 401 20.2 Treating Genetic Disease 402 Treating the Phenotype 402 Gene Therapy 403 Gene Delivery 404 20.3 Three Gene Therapies 408 An Early Success 408 A Major Setback 410 A Success in the Making 411 20.4 A Closer Look: Treating Sickle Cell Disease 413 20.5 Perspective: A Slow Start, But Great Promise 413 Chapter 21 Reproductive Technologies 417 21.1 Infertility and Subfertility 418 Male Infertility 418 Female Infertility 419 Infertility Tests 420 21.2 Assisted Reproductive Technologies 421 Donated Sperm?Intrauterine Insemination 421 A Donated Uterus?Surrogate Motherhood 423 In Vitro Fertilization 423 Gamete and Zygote Intrafallopian Transfer 425 Oocyte Banking and Donation 425 Preimplantation Genetic Diagnosis 426 21.3 Extra Embryos 428 Chapter 22 The Age of Genomics 433 22.1 How Genetics Became Genomics 434 22.2 The Human Genome Project Begins 435 The Sanger Method of DNA Sequencing 435 Many Goals 438 22.3 Technology Drives the Sequencing Effort 439 22.4 -Comparative Genomics 441 22.5 Into the Future 445 Epilogue: Genome Information Will Affect You 446 Answers to End-of-Chapter Questions A-1 Glossary G-1 Credits C-1 Index I-1

Table of 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 Levels of Genetics 5 DNA 5 Genes, Chromosomes, and Genomes 5 Cells, Tissues, and Organs 6 Individual 6 Family 6 Population 6 Evolution 8 1.3 Most Genes Do Not Function Alone 9 1.4 Statistics Represent Risks 10 1.5 Applications of Genetics 11 Establishing Identity and Origins 12 Health Care 14 Agriculture 15 Ecology 16 Genetics from a Global Perspective 17 Chapter 2 Cells 21 2.1 The Components of Cells 22 Chemical Constituents of Cells 22 Organelles 24 The Plasma Membrane 29 The Cytoskeleton 30 2.2 Cell Division and Death 33 The Cell Cycle 33 Apoptosis 36 2.3 Cell-Cell Interactions 37 Signal Transduction 37 Cellular Adhesion 38 2.4 Stem Cells and Cell Specialization 39 Cell Lineages 39 Using Embryos 39 Using Somatic Cells 42 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 Formation 53 Oocyte Formation 55 3.4 Prenatal Development 56 Fertilization 56 Cleavage and Implantation 56 The Embryo Forms 58 Supportive Structures Form 59 Multiples 60 The Embryo Develops 62 The Fetus Grows 62 3.5 Birth Defects 64 The Critical Period 64 Teratogens 64 3.6 Maturation and Aging 67 Adult-Onset Inherited Disorders 67 Disorders That Resemble Accelerated Aging 67 Is Longevity Inherited? 68 PART TWO Transmission Genetics 75 Chapter 4 Mendelian Inheritance 75 4.1 Following the Inheritance of One Gene?Segregation 76 Mendel the Man 76 Mendel?s Experiments 76 Terms and Tools to Follow Segregating Genes 77 4.2 Single-Gene Inheritance in Humans 80 Modes of Inheritance 80 On the Meaning of Dominance and Recessiveness 85 4.3 Following the Inheritance of Two Genes?Independent Assortment 85 Mendel?s Second Law 85 4.4 Pedigree Analysis 88 Pedigrees Then and Now 88 Pedigrees Display Mendel?s Laws 89 Chapter 5 Extensions and Exceptions to Mendel?s Laws 95 5.1 When Gene Expression Appears to Alter Mendelian Ratios 96 Lethal Allele Combinations 96 Multiple Alleles 96 Different Dominance Relationships 97 Epistasis?One Gene Affects Another?s Expression 98 Penetrance and Expressivity 99 Pleiotropy?One Gene, Many Effects 99 Phenocopies?When It?s Not in the Genes 100 Genetic Heterogeneity?More Than One Way to Inherit a Trait 100 The Human Genome Sequence Adds Perspective 101 5.2 Maternal Inheritance and Mitochondrial Genes 101 Mitochondrial Disorders 102 Heteroplasmy Complicates Mitochondrial Inheritance 103 Mitochondrial DNA Studies Clarify the Past 103 5.3 Linkage 103 Linkage Was Discovered in Pea Plants 103 Linkage Maps 104 The Evolution of Gene Mapping 107 Chapter 6 Matters of Sex 113 6.1 Sexual Development 114 Sex Chromosomes 114 The Phenotype Forms 115 Is Homosexuality Inherited? 118 6.2 Traits Inherited on Sex Chromosomes 120 X-Linked Recessive Inheritance 121 X-Linked Dominant Inheritance 122 6.3 X Inactivation Equalizes the Sexes 126 6.4 Sex-Limited and Sex-Influenced Traits 128 Sex-Limited Traits 128 Sex-Influenced Traits 128 6.5 Genomic Imprinting 129 Silencing the Contribution From One Parent 129 Imprinting Disorders in Humans 130 A Sheep With a Giant Rear End 131 Chapter 7 Multifactorial Traits 135 7.1 Genes and the Environment Mold Most Traits 136 Polygenic Traits Are Continuously Varying 136 Fingerprint Patterns 136 Height 137 Eye Color 137 Skin Color 138 7.2 Methods Used to Investigate Multifactorial Traits 140 Empiric Risk 140 Heritability 141 Adopted Individuals 143 Twins 144 Association Studies 146 7.3 Two Multifactorial Traits 148 Heart Health 148 Weight 149 Chapter 8 The Genetics of Behavior 155 8.1 Genes Contribute to Most Behavioral Traits 156 8.2 Eating Disorders 159 8.3 Sleep 160 Narcolepsy 160 Familial Advanced Sleep Phase Syndrome 161 8.4 Intelligence 161 8.5 Drug Addiction 163 8.6 Mood Disorders 164 8.7 Schizophrenia 165 PART THREE DNA and Chromosomes 171 Chapter 9 DNA Structure and Replication 171 9.1 Experiments Identify and Describe the Genetic Material 172 DNA Is the Hereditary Molecule 172 Protein Is Not the Hereditary Molecule 172 Discovering the Structure of DNA 173 9.2 DNA Structure 175 9.3 DNA Replication?Maintaining Genetic Information 179 Replication Is Semiconservative 179 Steps of DNA Replication 181 Chapter 10 Gene Action:From DNA to Protein 185 10.1 Transcription 186 RNA Structure and Types 186 Transcription Factors 188 Steps of Transcription 189 RNA Processing 190 10.2 Translation of a Protein 192 Deciphering the Genetic Code 192 Building a Protein 195 10.3 Protein Folding 197 Chapter 11 Control of Gene Expression 205 11.1 Gene Expression Through Time and Tissue 206 Globin Chain Switching 206 Building Tissues and Organs 207 Proteomics 208 11.2 Mechanisms of Gene Expression 209 Chromatin Remodeling 210 RNA Interference 210 11.3 Proteins Outnumber Genes 211 11.4 Most of the Human Genome Does Not Encode Protein 212 Noncoding (nc) RNAs 213 Repeats 213 Chapter 12 Gene Mutation 217 12.1 Mutations Can Alter Proteins?Three Examples 218 The Beta Globin Gene 218 Disorders of Orderly Collagen 219 Early-Onset Alzheimer Disease 220 Multiple Mutations Cause Confusion 221 12.2 Causes of Mutation 222 Spontaneous Mutation 222 Induced Mutation 224 Natural Exposure to Mutagens 225 12.3 Types of Mutations 226 Point Mutations 226 Splice Site Mutations 227 Deletions and Insertions Can Shift the Reading Frame 229 Pseudogenes and Transposons Revisited 229 Expanding Repeats 230 12.4 The Importance of Position 232 Globin Variants 232 Susceptibility to Prion Disorders 233 12.5 Factors That Lessen the Effects of Mutation 233 12.6 DNA Repair 234 Types of DNA Repair 234 DNA Repair Disorders 235 Chapter 13 Chromosomes 241 13.1 Portrait of a Chromosome 242 Telomeres and Centromeres Are Essential 242 Karyotypes Are Chromosome Charts 245 13.2 Visualizing Chromosomes 246 Obtaining Cells for Chromosome Study 246 Preparing Cells for Chromosome Observation 248 13.3 Abnormal Chromosome Number 251 Polyploidy 251 Aneuploidy 251 13.4 Abnormal Chromosome Structure 257 Deletions and Duplications 257 Translocations 258 Inversions 261 Isochromosomes and Ring Chromosomes 262 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 14.3 Applying Hardy-Weinberg Equilibrium 270 14.4 DNA Profiling Is Based on Hardy-Weinberg Assumptions 272 DNA Profiling Began with Forensics 273 Population Statistics Are Used to Interpret DNA Profiles 274 DNA Profiling to Identify Disaster Victims 278 14.5 Genetic Privacy 279 Chapter 15 Changing Allele Frequencies 283 15.1 Nonrandom Mating 284 15.2 Migration 286 Historical Clues 286 Geographical and Linguistic Clues 287 15.3 Genetic Drift 287 The Founder Effect 288 Population Bottlenecks 290 15.4 Mutation 291 15.5 Natural Selection 292 Tuberculosis Ups and Downs?and Ups 292 Evolving HIV 293 Balanced Polymorphism 295 15.6 Gene Genealogy 299 PKU Revisited 299 CF Revisited 300 Chapter 16 Human Origins