TY - BOOK AU - Lewis,Ricki TI - Human genetics: concepts and applications / SN - 9780073101439 U1 - 599.935 PY - 2007/// CY - Boston PB - McGraw-Hill, KW - Human genetics KW - Problems, exercises, etc KW - Chromosomes KW - Gene mapping N1 - 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 ER -