AN INTRODUCTION TO BEHAVIOR GENETICS Terence J. Bazzett Sinauer Associates, Inc. Publishers Sunderland, Massachusetts 01375
CONTENTS IN BRIEF PART I AN INTRODUCTION TO BEHAVIOR GENETICS 1 CHAPTER 1 Introducing Behavior Genetics: Origins and History 2 CHAPTER 2 The Basis of Genetics: DNA, RNA, Chromosomes, and Genes 24 CHAPTER 3 Neurogenetics and Neuropharmacology 54 CHAPTER 4 Methods of Genetic Discovery and the Human Genome Project 84 PART II HERITABILITY, ENVIRONMENTAL INFLUENCES, AND METHODS OF STUDY 113 CHAPTER 5 Simple Inheritance 114 CHAPTER 6 Inheritance of Complex Traits 144 CHAPTER 7 Genes and Environment 170 CHAPTER 8 Research Methods in Quantitative Genetics 202 PART III GENETIC INFLUENCES ON BEHAVIOR AND BEHAVIORAL DISORDERS 229 CHAPTER 9 Normal Behavioral Development 230 CHAPTER 10 Primary Cognitive Disorders 258 CHAPTER 11 Psychiatric Disorders with a Cognitive Component 288 CHAPTER 12 Disorders of Mood, Anxiety and Personality 318 PART IV OTHER GENETIC INFLUENCES, COUNSELING, AND THE FUTURE 349 CHAPTER 13 Beyond Psychotherapy: General Health Risks and Sex Chromosome Abnormalities 350 CHAPTER 14 Genetic Counseling, Applied Pharmacogenomics, and Gene Therapy 376 CHAPTER 15 The Future of Behavior Genetics 402
TABLE OF CONTENTS PART I AN INTRODUCTION TO BEHAVIOR GENETICS 1 CHAPTER 1 Introducing Behavior Genetics: Origins and History 2 DEFINING BEHAVIOR GENETICS 4 Effects of genetics on physical development 4 Effects of genetics on behavior 6 The influence of environment on physical development and behavior 8 ORIGINS OF BEHAVIOR GENETICS 11 A brief history 11 Relationship to behavioral pharmacology 16 WHAT TO EXPECT FROM THIS TEXT 17 Useful background knowledge 17 Chapter content and organization 18 CHAPTER SUMMARY 21 CHAPTER 2 The Basis of Genetics: DNA, RNA, Chromosomes, and Genes 24 DNA 26 Structure 27 Function 33
VIII TABLE OF CONTENTS RNA 35 Structure 35 Function 35 CHROMOSOMES 39 How many chromosomes are there in humans? 40 How many chromosomes are there in nonhuman species? 43 GENES 43 How many genes are there in humans? 44 How many genes are there in nonhuman species? 45 GENE FUNCTION 46 What does the genetic blueprint look like? 47 What happens when gene function is abnormal? 49 CHAPTER SUMMARY 50 CHAPTER 3 Neurogenetics and Neuropharmacology 54 NEUROGENETICS 56 Neuronal structure 56 Neuronal function: Propagating a neuronal signal 58 Neuronal function: Initiating a neuronal signal 62 Influence of genes on neuronal structure and function 64 The basics of agonist and antagonist pharmacotherapy 70 The basics of neuroprotectant pharmacotherapy 75 An introduction to pharmacogenomics 76 Psychiatric disorders and pharmacogenomics 78 CHAPTER SUMMARY 80 CHAPTER 4 Methods of Genetic Discovery and the Human Genome Project 84 VISUALIZING DNA 86 The polymerase chain reaction 86 Electrophoresis 91 DNA fingerprinting 93 Further applications of DNA analysis 95 THE HUMAN GENOME PROJECT 97 What is the Human Genome Project? 99 Positive implications 102 Negative implications 105 Legal implications 107 Keeping the facts straight 108 CHAPTER SUMMARY 109 NEUROPHARMACOLOGY 67 The synapse 68
TABLE OF CONTENTS IX PART II HERITABILITY, ENVIRONMENTAL INFLUENCES, AND METHODS OF STUDY 113 CHAPTER 5 Simple Inheritance 114 QUALITATIVE VERSUS QUANTITATIVE TRAITS 116 MENDEL S LAWS 122 BEYOND MENDEL S LAWS: SPECIAL PATTERNS OF INHERITANCE 128 Linkage and recombination 129 Gene conversion 133 Translocation 134 Spontaneous mutations 134 Genetic anticipation 135 Genomic imprinting 137 MITOCHONDRIAL DNA 138 Mitochondrial inheritance 138 Defective mitochondrial DNA 139 Defective mitochondrial DNA versus mitochondrial disorders 141 CHAPTER SUMMARY 141 CHAPTER 6 Inheritance of Complex Traits 144 PATTERNS NOT READILY PREDICTED BY MENDEL S LAWS 146 Polygenic traits 146 Polygenic traits in animals as a model for human behaviors 148 ESTABLISHING QTL 152 Linkage analysis 152 Basic considerations in QTL analysis 155 Discrepancies between normal curves for populations and for patients 157 Environmental factors 160 THE ROLE OF QTL IN NORMAL AND ABNORMAL FUNCTION 160 Cognitive development and intelligence 161 Schizophrenia 163 CHAPTER SUMMARY 166 CHAPTER 7 Genes and Environment 170 EVOLUTION 172 The contributions of Charles Darwin 172 Implications of genetic diversity 175 Factors influencing evolution 176 Human evolution: Perspectives on behavior 178 ENVIRONMENTAL EFFECTS ON GENETICS AND BEHAVIOR 181 Gene environment interaction 182 Prenatal environmental effects 182 Postnatal environmental effects 189 Environmentally induced mutations 191 Gene environment correlation 191 NATURE VERSUS NURTURE 194 Debate? What debate? 194 Reconsidering Watson s claim 196 CHAPTER SUMMARY 198
X TABLE OF CONTENTS CHAPTER 8 Research Methods in Quantitative Genetics 202 DEFINING HERITABILITY 204 Qualitative traits revisited 204 Quantitative traits revisited 205 ANIMALS 208 History of animal models 208 Trait breeding 208 Inbreeding 212 Transgenic models 214 HUMANS 215 Familial patterns 216 Twin studies 218 Adoption studies 221 CHAPTER SUMMARY 226 PART III GENETIC INFLUENCES ON BEHAVIOR AND BEHAVIORAL DISORDERS 229 CHAPTER 9 Normal Behavioral Development 230 WHAT IS NORMAL BEHAVIOR? 232 COGNITIVE ABILITIES 234 The g factor 234 Breeding for intelligence in animals 236 Human intelligence 240 PERSONALITY TRAITS 243 Breeding for temperament in animals 243 Human personality traits 247 SEXUAL BEHAVIOR 249 Influence of genes on heterosexual behavior 250 Influence of genes on homosexual behavior 252 CHAPTER 10 Primary Cognitive Disorders 258 MENTAL RETARDATION 260 Severity range 260 Prevalence 261 Genetic influences 263 Heritability 270 DEMENTIA 272 Prevalence 272 Genetic influences 274 Heritability 277 LEARNING DISABILITIES 278 Prevalence 280 Genetic influences 282 Heritability 282 CHAPTER SUMMARY 285 CHAPTER SUMMARY 255
TABLE OF CONTENTS XI CHAPTER 11 Psychiatric Disorders with a Cognitive Component 288 SCHIZOPHRENIA 290 Prevalence 290 Genetic influences 291 Heritability 295 AUTISM 297 Prevalence 298 Genetic influences 300 Heritability 301 EATING DISORDERS 301 Prevalence 302 Genetic influences 303 Heritability 304 ADDICTIVE BEHAVIOR 306 Prevalence 307 Genetic influences 310 Heritability 313 CHAPTER SUMMARY 314 CHAPTER 12 Disorders of Mood, Anxiety and Personality 318 MOOD DISORDERS 320 Prevalence 320 Genetic influences 323 Heritability 327 ANXIETY DISORDERS 329 Prevalence 331 Genetic influences 332 Heritability 335 PERSONALITY DISORDERS 336 Prevalence 336 Genetic influences 339 Heritability 341 CHAPTER SUMMARY 344 PART IV OTHER GENETIC INFLUENCES, COUNSELING, AND THE FUTURE 349 CHAPTER 13 Beyond Psychotherapy: General Health Risks and Sex Chromosome Abnormalities 350 HEALTH PSYCHOLOGY 352 Health and behavior 352 Psychophysiological illness 354 CARDIOVASCULAR DISEASE 356 Hypertension 356 Acute cardiovascular disease 357 Influence of personality type 357 OBESITY 359 An evolutionary perspective 359 Genetic contributions 361 SEX CHROMOSOMES: STRUCTURAL DISPARITIES AND THEIR CONSEQUENCES 361 Gene inheritance patterns 363 Deletions and additions 367 CHAPTER SUMMARY 372
XII TABLE OF CONTENTS CHAPTER 14 Genetic Counseling, Applied Pharmacogenomics, and Gene Therapy 376 GENETIC COUNSELING 378 What is genetic counseling? 378 What kinds of information do genetic counselors interpret? 379 What kinds of recommendations do genetic counselors make? 386 APPLIED PHARMACOGENOMICS 388 Revisiting basic concepts 389 Application of current understanding: Schizophrenia 390 Application of current understanding: Depression 392 GENE THERAPY 393 Historical perspective 394 Applying current knowledge to behavior genetics 395 CHAPTER 15 The Future of Behavior Genetics 402 REVIEWING THE PAST WITH AN EYE TO THE FUTURE 404 Future applications of the Human Genome Project 404 The future of genetic counseling 405 The future of gene therapy 410 THE FUTURE OF BEHAVIOR GENETICS EDUCATION 413 Educating the public 413 Advanced degrees in genetic counseling 415 Advanced degrees in behavior genetics 419 CHAPTER SUMMARY 421 CHAPTER SUMMARY 397 GLOSSARY 425 PHOTO CREDITS 445 REFERENCES 447 INDEX 459