Neurobehavioral Genetics: Methods and Applications, Second Edition

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ISBN: 9780849319037 | 084931903X
Cover: Hardcover
Copyright: 8/30/2006

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A complete background to concepts and principles of behavioral genetics, Neurobehavioral Genetics: Methods and Applications, Second Edition features a broad spectrum of the most current techniques in neurobehavioral genetics in a single source.International researchers incorporate several new developments in the field, including:· Developmental neurobehavioral genetics· Gene-gene interaction· New approaches in bioinformatics· Gene expression· Single gene techniquesBased on various studies of living organisms ranging from primates to rodents to invertebrates, this edition offers a contemporary approach to examining the relationship between the genetic mechanisms in the brain and behavior. The authors examine how past and recent advances in methods and knowledge come together in the comparative genetics of behavior. They introduce the reader to experimental approaches available for the genetic study of emotionality, focusing on the use of animal models.This edition explores studies in neurogenetic disorders, including schizophrenia and bipolar disorders, examines genetic traits in personality such as altruism, and evaluates aggression in mice and humans. It also discusses the applications of quantitative methods and molecular genetics in basic and clinical research.Neurobehavioral Genetics: Methods and Applications, Second Edition brings together new techniques and methods to promote a better understanding of genetics and their effects on behavior. The book is an excellent resource for investigators who want to incorporate genetic methods into neurobehavioral and psychiatric research.

Chapter 1 A History of Behavior Genetics

(16)

Stephen C. Maxson

Summary

(1)

1.1 Introduction

(1)

1.2 Preliterate and Ancient History

(1)

1.3 Two Victorian Cousins

(1)

1.4 The First Century of Behavior Genetics

(9)

1.4.1 1910 to 1952

(1)

1.4.1.1 Fruit Flies

(1)

1.4.1.2 Rodents

(1)

1.4.1.3 Humans

(1)

1.4.2 1953 to 1970

(3)

1.4.2.1 Fruit Flies

(1)

1.4.2.2 Rodents

(1)

1.4.2.3 Dogs

(1)

1.4.2.4 Humans

(1)

1.4.3 1971 to 1985

(2)

1.4.3.1 Nematodes

(1)

1.4.3.2 Fruit Flies

(1)

1.4.3.3 Rodents

(2)

1.4.3.4 Canids

(1)

1.4.3.5 Humans

(1)

1.4.4 1986 to 2005

(21)

1.4.4.1 Nematodes

(1)

1.4.4.2 Fruit Flies

(1)

1.4.4.3 Bees

(1)

1.4.4.4 Rodents

(1)

1.4.4.5 Humans

(1)

1.5 Janus: The Past and Future of Behavior Genetics

(1)

1.6 A Highly Personal Note

(1)

References

(3)

Chapter 2 Developmental Neurobehavioral Genetics: Development as Explanation

(12)

Gilbert Gottlieb

Introduction

(1)

2.1 Preformation and Epigenesis

(2)

2.2 Development as Explanation

(5)

2.3 A Currently Acceptable Developmental Neurobehavioral Genetics: Interim Solution

(2)

2.4 Summary and Conclusions

(1)

Acknowledgments

(1)

References

(3)

Chapter 3 Some Basics, Mendelian Traits, Polygenic Traits, Complex Traits

(8)

Byron C. Jones

3.1 Introduction and Levels of Investigation

(1)

3.2 Fundamental Questions. What Causes What?

(1)

3.3 Phenotypes and Phenotypic Selection

(1)

3.4 Genotype—Phenotype Relationships

(1)

3.5 Mendel's Laws

(1)

3.5.1 Law of Segregation

(1)

3.5.2 Law of Independent Assortment

(1)

3.6 Linkage

(1)

3.7 Mendelian Traits

(1)

3.7.1 Recessively Transmitted Traits

(1)

3.7.2 Dominant Traits

(1)

3.8 Complex Traits and Additive Genetic Effects

(1)

3.9 Interactions

(1)

3.9.1 Gene—Environment Interactions

(1)

3.9.2 Gene—Gene Interactions

(1)

3.10 Summary

(1)

References

(2)

Summary

(1)

Chapter 4 An Introduction to Quantitative Genetics

(18)

Wim E. Crusio

4.1 Introduction

(1)

4.2 Phylogenetic Aspects of Causation

(5)

4.2.1 Natural Selection and Genetic Architecture

(1)

4.2.2 Theoretical Background

(4)

4.2.3 Examples

(1)

4.3 Phenogenetic Aspects of Causation

(6)

4.3.1 The Correlational Approach: Brain Lesions and the Locality Assumption

(1)

4.3.2 Genetic Correlations

(1)

4.3.3 Theoretical Background

(3)

4.3.4 Examples

(8)

4.3.4.1 Rearing Behavior in an Open Field and Hippocampal Mossy Fibers in Mice

(1)

4.3.4.2 Nerve Conduction Velocity and IQ in Man

(1)

4.3.4.3 Localization of QTL

(1)

4.4 Some Common Misapplications

(2)

4.5 Conclusion

(1)

Acknowledgments

(1)

References

(2)

Appendix

(1)

Chapter 5 From QTL Detection to Gene Identification

(18)

Marie-Pierre Moisan

Summary

(1)

5.1 Introduction

(1)

5.2 High-Resolution Mapping

(6)

5.2.1 Congenic Strains and Substrains

(3)

5.2.2 Alternative Strategies

(3)

5.3 Positional Cloning

(5)

5.3.1 Pure Positional Cloning

(2)

5.3.2 Positional Candidate Approach

(32)

5.3.2.1 Mapping of Candidate Genes in the QTL

(1)

5.3.2.2 Combining QTL Mapping and Expression Profiling

(1)

5.3.2.3 Haplotype Mapping

(1)

5.4 Conclusion

(1)

References

(6)

Chapter 6 Gene Expression

(22)

Richard A. Radcliffe

Introduction

(1)

6.1 The Gene

(2)

6.2 Transcription: Basic Mechanism of mRNA Biogenesis

(4)

6.3 Regulation of Transcription

(3)

6.4 Transcriptional Regulation through Signal Transduction

(2)

6.5 RNA Interference

(1)

6.6 Gene Silencing

(1)

6.7 Sources of Variation in Gene Expression

(1)

6.8 Measuring Gene Expression

(4)

References

(4)

Summary

Chapter 7 Bioinformatics of Behavior

(20)

Elissa J. Chesler

7.1 What Is Bioinformatics?

(1)

7.2 Database Design

(2)

7.2.1 Data Storage beyond the Spreadsheet: Laboratory Information Management Systems (LIMS)

(1)

7.2.2 Data Modeling

(1)

7.2.2.1 The Flat Format

(1)

7.2.2.2 The Hierarchical Format

(1)

7.2.2.3 The Relational Database Management System (RDBMS)

(1)

7.3 "Natural" Keys in Biological Databases

(5)

7.3.1 Genome Location as Reference

100

(1)

7.3.2 Genes as References

100

(1)

7.3.3 Genetic Reference Populations

101

(3)

7.3.3.1 Genetic Correlations and Reference Populations

102

(1)

7.3.3.2 GRPs for Mapping QTLs

103

(1)

7.3.4 Gene Sets as References

104

(1)

7.3.4.1 Gene Ontology

104

(1)

7.3.4.2 The Interactome

104

(1)

7.4 Applications

104

(6)

7.4.1 Sequence Analysis Scoring Matrices and Phylogeny

105

(2)

7.4.1.1 Scoring Matrices

106

(1)

7.4.1.2 Motif Search and Alignment

106

(1)

7.4.1.3 Structure Analysis

106

(1)

7.4.2 QTL Candidate Gene Selection

107

(1)

7.4.3 Microarray, Proteomic, and Other High-Throughput Gene Set Analysis

108

(1)

7.4.4 Text Mining

109

(1)

7.4.5 Integrating the Genome and the Phenome for Systems-Level Bioinformatics

109

(1)

7.5 Toward a Bioinformatics of Behavior

110

(1)

Acknowledgments

111

(1)

References

111

(4)

Chapter 8 Congenic and Consomic Strains

115

(14)

Lorraine Flaherty and Valerie Bolivar

Introduction

115

(1)

8.1 Congenic Strains

116

(3)

8.2 Consomic Strains

119

(1)

8.3 Knockout/Congenic Strains

119

(4)

8.4 Mapping QTLs with Knockout/Congenic Mice

123

(3)

References

126

(3)

Chapter 9 Animal Resources in Behavioral Neurogenetics

129

(20)

Jean-Michel Lassalle

9.1 Introduction

130

(2)

9.1.1 Requirements for a Suitable Animal Model

130

(1)

9.1.2 The "Genome Club"

131

(1)

9.1.3 The Basic Principle of Animal Tools Is Inbreeding

131

(1)

9.2 Inbred Strains

132

(1)

9.2.1 Hybrid Crosses

132

(1)

9.2.1.1 Fl Hybrids

132

(1)

9.2.1.2 F2 Hybrids

133

(1)

9.3 Advanced Intercross Lines (AILs)

133

(1)

9.4 Strains That Differ Only by a Known Part of Their Genome

133

(3)

9.4.1 Co-Isogenic Strains

134

(1)

9.4.2 Congenic Strains

134

(1)

9.4.3 Consomic Strains or Chromosome Substitution Strains

134

(1)

9.4.4 Conplastic Strains

135

(1)

9.4.5 Selected Strains

136

(1)

9.5 Strains Made from (Multiple) Inbred Strains

136

(2)

9.5.1 Recombinant Inbred Strains (RIs)

136

(1)

9.5.1.1 Seven Major RI Sets Are Currently Available

136

(1)

9.5.2 Recombinant Congenic Strains (RCs)

137

(1)

9.5.3 Segregating Inbred Strains (SIs)

138

(1)

9.5.4 Mixed Inbred Strains (MIs)

138

(1)

9.6 Genetically Engineered Mutant Mice

138

(2)

9.6.1 Transgenic Mice

138

(1)

9.6.2 Mice with Targeted Mutations (Knockouts)

139

(1)

9.6.3 Mice with Chemically Induced Mutations

139

(1)

9.6.4 Chromosomal Aberration Strains

139

(1)

9.7 Other Strains

140

(1)

9.7.1 Outbred Strains or Outbred Colonies

140

(1)

9.7.2 Wild-Derived Inbred Mice

140

(1)

9.8 Origins of the Oldest Inbred Strains of Mice

140

(1)

9.9 Strains and Substrains of Laboratory Mice

141

(1)

9.10 International Supply of Mouse and Rat Research Models

142

(1)

9.10.1 The Jackson Laboratory and Charles River Laboratories

142

(1)

9.10.1.1 Genetic Quality

143

(1)

9.10.1.2 Animal Health Quality

143

(1)

9.10.2 The Complex Trait Consortium (CTC)

143

(1)

9.11 Other Species of Interest for Behavioral Neurogenetics Research

143

(1)

9.11.1 Drosophila Melanogaster

143

(1)

9.11.2 Caenorhabditis Elegans

144

(1)

9.12 Useful Web Sites

144

(2)

9.12.1 Web Sites for the Mouse and the Rat

145

(1)

9.12.2 Rodents' Suppliers

145

(1)

9.12.3 Web Sites for Drosophila

145

(1)

9.12.4 Web Sites for Caenorhabditis elegans

145

(1)

References

146

(3)

Chapter 10 Sample Size Requirements for Experiments on Laboratory Animals

149

(20)

Douglas Wahlsten

Introduction

149

(1)

10.1 Effect size

150

(2)

10.2 Probability of a False Positive

152

(2)

10.3 Probability of Failing to Detect Something Real

154

(1)

10.4 Estimating Effect Size from Published Data

155

(1)

10.5 Methods for Estimating Sample Size

156

(2)

10.6 Power and Sample Size for Two Independent Groups

158

(1)

10.7 Comparison of Several Inbred Strains

159

(2)

10.8 Comparing Specific Groups in a One-Way Design

161

(1)

10.9 Strain x Treatment Experiments

162

(3)

10.10 Bridging the Gap: the 2 x 2 Design

165

(2)

10.11 Sample Size for More Specialized Experiments

167

(1)

Acknowledgments

167

(1)

References

167

(2)

Chapter 11 The Role of Association Studies in Psychiatric Disorders

169

(14)

Nicolas Ramoz and Philip Gorwood

Introduction

169

(1)

11.1 Association Studies: Definitions and Mechanisms

170

(2)

11.1.1 Case Control Association Study

170

(1)

11.1.2 Family-Based Association Studies

171

(1)

11.2 Advantage of Association Studies

172

(1)

11.2.1 Power

172

(1)

11.2.2 Linkage Disequilibrium

173

(1)

11.3 Limitations of Association Studies

173

(3)

11.3.1 False Positives: Linkage Disequilibrium and Control Groups

174

(1)

11.3.2 Statistical Power: Accept or Reject an Association

175

(1)

11.3.3 Consequences in Neurobehavioral Genetics

175

(1)

11.4 Progress in Neurobehavioral Genetics

176

(4)

11.4.1 One Gene ... Many Phenotypes (the Case of Phenotypical Heterogeneity)

177

(1)

11.4.2 One Phenotype ... Many Genes (the Case of Genetic Heterogeneity)

177

(1)

11.4.3 Interaction between the Environment and Genetic Vulnerability

178

(2)

11.5 Conclusions

180

(1)

References

180

(3)

Chapter 12 Family and Twin Methods

183

(6)

Keith E. Whitfield and Tracy L. Nelson

12.1 Introduction 183

12.2 Behavioral Genetics and Health

183

(1)

12.3 General Behavioral Genetic Methods

184

(2)

12.4 Genetics, Environment, and Health: Integration of Approaches

186

(2)

Acknowledgments

188

(1)

References

188

(1)

Chapter 13 Gene–Environment Interactions

189

(12)

Byron C. Jones and Leslie C. Jones

13.1 Introduction: What Are Gene—Environment Interactions and Why Are They Important?

189

(1)

13.2 How Do Genes and Environments Cooperate?

190

(7)

13.2.1 Gene—Environment Correlation

190

(1)

13.2.1.1 Passive Genotype—Environment Correlation

190

(1)

13.2.1.2 Reactive Genotype—Environment Correlation

190

(1)

13.2.1.3 Active Genotype—Environment Correlation

190

(1)

13.2.2 Gene—Environment Interaction

190

(12)

13.2.2.1 Definition Vp = Vg + Ve + (Vgxe) + Vepsilon

191

(1)

13.2.2.2 Evidence for Gene—Environment

191

(1)

13.2.2.2.1 Genotype—Environment Interaction in Humans

191

(1)

13.2.2.2.2 Gene—Environment Interaction in Animals

195

(2)

13.3 Genera1 Considerations

197

(4)

References

Chapter 14 And Now it Starts to Get Interesting: Gene–Gene Interactions

201

(8)

Yamima Osher

14.1 Introduction

201

(1)

14.2 Epistasis

202

(1)

14.2.1 Two Genes, Interacting

202

(1)

14.2.2 Three Can Play, Too

203

(1)

14.3 Not Only in Humans

203

(1)

14.4 Gene—Gene Interactions in Common Human Diseases

204

(1)

14.5 Statistical Methods

204

(1)

14.6 Summary

205

(1)

References

205

(4)

Chapter 15 Schizophrenia: Study of a Genetically Complex Phenotype

209

(18)

Michael F. Pogue-Geile and Irving I. Gottesman

Abstract

209

(1)

15.1 Introduction

210

(1)

15.2 Defining the Phenotype

210

(1)

15.3 Does Genetic Variation Contribute to the Etiology of Schizophrenia?

211

(5)

15.3.1 Family Studies

211

(2)

15.3.2 Twin Studies

213

(1)

15.3.3 Adoption Studies

214

(2)

15.4 What Is the Nature of Genetic Effects on Schizophrenia?

216

(3)

15.4.1 Only Genetic Effects?

216

(1)

15.4.2 How Many Genes?

217

(2)

15.5 Where on the Chromosomes Are Schizophrenia Liability Genes Located?

219

(1)

15.6 Which Genes Contribute to Schizophrenia Liability?

220

(2)

15.7 Conclusions

222

(1)

References

222

(5)

Chapter 16 Genetics of Major Affective Disorders

227

(20)

Wade Berrettini

Introduction

227

(1)

16.1 Bipolar Disorders

228

(8)

16.1.1 Genetic Epidemiology: Family Studies

228

(1)

16.1.2 Genetic Epidemiology: Twin Studies

228

(2)

16.1.3 Molecular Linkage Studies

230

(1)

16.1.4 Linkage Disequilibrium Studies

231

(5)

16.2 Recurrent Unipolar Disorders

236

(1)

16.2.1 Genetic Epidemiology: Family Studies

236

(1)

16.2.2 Genetic Epidemiology: Twin Studies

237

(1)

16.2.3 Molecular Linkage Studies

237

(1)

Summary

237

(1)

References

238

(9)

Chapter 17 Pedigree Analyses and the Study of Chimpanzee (Pan troglodytes) Personality and Subjective Well-Being

247

(16)

Alexander Weiss and James E. King

17.1 Overview

248

(3)

17.1.1 Chimpanzee Natural History and Behavior

249

(1)

17.1.2 Human and Chimpanzee Personality

249

(1)

17.1.3 Human and Chimpanzee Subjective Well-Being

250

(1)

17.1.4 Study Goals

250

(1)

17.1.4.1 Reasons for Using Pedigree Analysis Methods

250

(1)

17.1.4.2 Common Features of Pedigree Analysis Methods

250

(1)

17.2 Symmetric Differences Squared

251

(3)

17.2.1 Squared Phenotypic Differences and the Variance

251

(2)

17.2.1.1 A Latent Variable Model for Estimating Variances and Covariances

251

(1)

17.2.1.2 Using Multiple Regression to Solve for Variance Estimates

252

(1)

17.2.1.3 Computing Proportions of Variance

252

(1)

17.2.2 Results When Using Symmetric Differences Squared

253

(1)

17.2.3 Additional Considerations

253

(1)

17.2.3.1 Advantages of Symmetric Differences Squared

253

(1)

17.2.3.2 Least Squares Estimation and Negative Variance Components

253

(1)

17.2.3.3 Using Monte Carlo Procedures to Determine Statistical Significance

254

(1)

17.2.4 Concluding Thoughts

254

(1)

17.3 Multitrait Derivative Free Restricted Maximum Likelihood Analysis

254

(3)

17.3.1 Foundations of the Univariate Case

254

(1)

17.3.1.1 Henderson's Mixed Model Equation and the Estimation of Variance and Covariance Components

254

(1)

17.3.2 Study Goals

255

(1)

17.3.2.1 Choosing a Model Using Akaike's Information Criterion

256

(1)

17.3.2.2 Comparing Nested Models Using Chi-Square Tests

256

(1)

17.3.3 Considerations

256

(1)

17.3.3.1 Advantages of Using Multitrait Derivative Free Restricted Maximum Likelihood Analysis

257

(1)

17.3.3.2 Drawbacks of Using Multitrait Derivative Free Restricted Maximum Likelihood Analysis

257

(1)

17.4 Concluding Thoughts and Other Uses For Multitrait Derivative Free Restricted Maximum Likelihood Analysis

257

(1)

17.4.1 Other Applications of Multitrait Derivative Free Restricted Maximum Likelihood Analysis

257

(1)

17.4.1.1 Genetic Association Studies

257

(1)

17.4.1.2 Environmental Association Studies

258

(1)

17.4.1.3 Assessing Gene x Environment Interactions

258

(1)

17.4.2 Concluding Thoughts

258

(1)

Author's Note

258

(1)

References

259

(2)

Appendix A: Using Animal Breeder's Toolkit to Compute Relatedness Among Individuals within a Pedigree

261

(2)

Chapter 18 The Elusive World of Personality Genes: Cherchez le Phenotype

263

(18)

Richard P. Ebstein, Rachel Bachner-Melman, Jonathan Benjamin, and Robert H. Belmaker

18.1 Personality

263

(3)

18.1.1 What Is Personality and How Is It Measured?

263

(3)

18.2 Heritability

266

(1)

18.3 Molecular Genetics

266

(1)

18.4 Related Phenotypes

267

(3)

18.4.1 Fibromyalgia

267

(1)

18.4.2 Altruism

268

(2)

18.5 The Social Personality

270

(1)

18.6 Linkage Studies

271

(2)

18.7 Importance

273

(1)

Acknowledgments

273

(1)

References

273

(8)

Summary

281

(1)

Chapter 19 Aggression: Concepts and Methods Relevant to Genetic Analyses in Mice and Humans

281

(10)

Stephen C. Maxson and Andrew Canastar

19.1 Introduction

282

(1)

19.2 Mice

282

(4)

19.3 Humans

286

(1)

19.4 Mice and Humans

287

(1)

References

288

(3)

Summary

291

(1)

Chapter 20 Genetic Analysis of Emotional Behaviors Using Animal Models

291

(16)

André Ramos and Pierre Mormède

20.1 Introduction

291

(1)

20.2 Definitions

292

(1)

20.3 Measurements

292

(6)

20.3.1 Unconditioned Stress Responses, Forced Exposure

293

(2)

20.3.2 Unconditioned Stress Responses, Choice Tests

295

(1)

20.3.3 Conditioning Experiments

295

(1)

20.3.4 Interpreting Emotionality through a Multivariate Approach

296

(2)

20.4 Genetic Analysis

298

(5)

20.4.1 Selection Experiments

298

(1)

20.4.2 Quantitative Genetic Analysis

299

(700)

20.4.3 Genetic Links between Different Traits

999

20.4.4 The QTL Chase

300

(3)

20.4.5 Gene Targeting and Transgenesis

303

(1)

References

303

(4)

Chapter 21 Genetic Analysis of Food Search Behavior in the Fruit Fly (Drosophila melanogaster)

307

(12)

Amsale T. Belay and Marla B. Sokolowski

Introduction

307

(1)

21.1 The Fruit Fly D. melanogaster as a Model Organism

308

(1)

21.2 Polygenic and Single-Gene Analysis

308

(3)

21.2.1 Polygenic Analysis

309

(1)

21.2.2 Single-Gene Analysis

309

(1)

21.2.3 Polygenic vs. Single-Gene Analysis of Behavior

310

(1)

21.3 Food Search Behavior

311

(1)

21.4 Role of the Foraging Gene in Other Organisms

312

(2)

Acknowledgments

314

(1)

References

314

(5)

Chapter 22 Genetic and Molecular Analyses of Drosophila Courtship Behavior

319

(14)

Jean-Marc Jallon

22.1 Introduction

319

(1)

22.2 Mating Behavior of Drosophila melanogaster, Visual and Acoustic Stimuli

320

(1)

22.3 Pheromones and Biosynthetic Genes

321

(3)

22.4 Gustatory and Olfactory Receptors

324

(2)

22.5 Sex Determination Cascade and the Courtship Behavior Master Gene Fruitless

326

(2)

References

328

(5)

Chapter 23 A New Era for Drosophila Learning and Memory Studies

333

(20)

Daniel Comas, Guillaume Isabel, and Thomas Préat

Introduction

333

(5)

23.1 Visualizing Neuronal Circuits Thanks to Genetics

338

(1)

23.2 Imaging Brain Activity

339

(1)

23.3 Learning and Memory Mutants

340

(1)

23.4 Temporal Control of Gene Expression

341

(2)

23.5 A Tool to Build Anatomo-Functional Maps

343

(1)

23.6 Localization of Olfactory Memory in Drosophila MBs

343

(2)

23.7 Dynamic of Olfactory Memory Phases in Drosophila

345

(3)

References

348

(5)

Chapter 24 Behavioral Genetics in the Nematode Caenorhabditis elegans

353

(18)

Gert Jansen and Laurent Ségalat

24.1 Summary

353

(1)

24.2 C. elegans as a Model Organism

353

(2)

24.2.1 C. elegans Has a Very Simple Nervous System

353

(2)

24.2.2 C. elegans Is Well Suited for Genetic Studies

355

(1)

24.3 Behaviors of C. elegans and Mutations Affecting Them

355

(12)

24.3.1 Chemosensory Behavior and Its Plasticity

356

(3)

24.3.2 Egg Laying

359

(2)

24.3.3 Regulation of Locomotion in Response to Food

361

(1)

24.3.4 Ethanol Resistance

362

(1)

24.3.5 Social Feeding Behavior

363

(1)

24.3.6 Memory

364

(3)

24.4 Conclusion

367

(1)

References

367

(2)

Authors' Note

369

(2)

Chapter 25 Genetics, Behavior, and Brain Dopamine Systems

371

(18)

Robert Hitzemann, Shannon McWeeney, and John Belknap

25.1 Introduction

371

(2)

25.2 A Behavioral Approach—The Catalepsy Phenotype

373

(3)

25.3 From Transporter and Receptor Density to Behavioral Phenotypes

376

(3)

25.4 D2 Dopamine Receptor Density and Drd2 Expression

379

(6)

25.5 Regulation of Drd2 Expression

385

(1)

25.6 Conclusions

386

(1)

Acknowledgments

386

(1)

References

387

(2)

Chapter 26 Natural Genetic Variation of Hippocampal Structures and Behavior—an Update

389

(22)

Hans-Peter Lipp, Irmgard Amrein, Lutz Slomianka, and David P. Wolfer

Abstract

389

(1)

26.1 Introduction

390

(1)

26.2 The Hippocampal Mossy Fiber Projection

391

(1)

26.3 Selectively Bred Strains as Tools for Testing Brain–Behavior Relations

392

(1)

26.4 Verifying Association between Traits: Genetic and Phenotypic Correlations

393

(1)

26.5 Solutions for the Linkage Problem

394

(2)

26.6 Extending the Behavioral Analysis: Correlations with Other Hippocampus-Dependent Tasks

396

(3)

26.7 Searching for "Non Hippocampal" Behavioral Correlates

399

(2)

26.8 Conflicting Data

401

(1)

26.9 Emerging Hypotheses

402

(1)

26.10 Some More Problems

403

(1)

26.11 The Real World Test for Genetic Brain–Behavior Relations: Natural Selection and Evolution

403

(3)

26.12 Conclusions and Outlook

406

(1)

Acknowledgments

407

(1)

References

408

(2)

List of Abbreviations in Text

410

(1)

Chapter 27 Expression and Brain Structure: Black Boxes between Genes and Behaviors

411

(24)

Jeremy L. Peirce and Robert W. Williams

27.1 Introduction

412

(1)

27.2 Genes and Development

412

(1)

27.3 Brains and Behavior

412

(1)

27.4 Dealing with Complexity

413

(1)

27.5 Complex Trait Analysis and Quantitative Trait Loci (QTL) Mapping

413

(2)

27.6 The Value of Genetic Reference Populations

415

(1)

27.7 Microarray Data: The Cheapest, Highest Throughput Phenotype

416

(1)

27.8 Microarray Data: Caveats from Complex Tissue

417

(1)

27.9 mRNA Abundance QTLs

417

(1)

27.10 Cis-Acting QTLs and Trans-Acting QTLs

418

(1)

27.11 mRNA Is Not protein

419

(1)

27.12 From QTL to Gene

419

(1)

27.13 Data Sets in GeneNetwork

419

(2)

27.14 Genetic Correlation

421

(2)

27.15 Clustering and Networks

423

(1)

27.16 Cluster Tree

423

(1)

27.17 Network Graph

423

(1)

27.18 More to Do with a Gene List: WebGestalt and Related Tools

423

(1)

27.19 Back to the Brains Mouse Brain Library (MBL)

424

(1)

27.20 Putting the Pictures Together

425

(1)

27.21 Allen Brain Atlas (ABA)

426

(1)

27.22 GENSAT

426

(3)

27.22.1 Example: Mapping Dentate Gyrus Volume

426

(2)

27.22.2 Example: Ror2 and Msx2 as Candidate Genes for DGV13a

428

(1)

27.23 A Side Note on the Problems of Specificity and Power

429

(1)

27.24 Conclusion

430

(1)

References

430

(5)

Chapter 28 Synaptic Mechanisms Involved in Cognitive Function: Cues from Mental Retardation Genes

435

(14)

Guntram Borck, Florence Molinari, Birgit Dreier, Peter Sonderegger, and Laurence Colleaux

28.1 Introduction

436

(1)

28.2 At the Beginning Was the X

436

(6)

28.2.1 NS-MR Genes Involved in the Regulation of the Actin Cytoskeleton: Possible Roles for the Adaptive Response of Postsynaptic Spines

437

(2)

28.2.1.1 Oligophrenin-1

438

(1)

28.2.1.2 PAK3 (p21 Activated Kinase 3)

438

(1)

28.2.1.3 αPIX or Cool-2

439

(1)

28.2.2 Nonsyndromic MR Genes Involved in the Regulation of Presynaptic Neurotransmitter Release

439

(3)

28.2.2.1 RabGDI1 (Rab GDP-Dissociation Inhibitor 1)

441

(1)

28.2.2.2 IL1RAPL1 (Interleukin-1 Receptor Accessory Protein-Like1)

441

(1)

28.2.2.3 FACL4 (Fatty Acid-CoA Ligase 4)

441

(1)

28.3 Lessons from the X

442

(1)

28.4 Neurotrypsin, a Nonsyndromic MR Gene with Synaptic Localization but Unknown Function

442

(2)

28.4.1 Neurotrypsin Mutation in Autosomal Recessive MR

443

(1)

28.5 What Do Nonsyndromic MR Genes Tell Us about the Cellular Mechanisms That Are Important for Cognitive Functions?

444

(1)

References

445

(4)

Chapter 29 Pharmacogenetics

449

(8)

Byron C. Jones

29.1 Introduction

449

(1)

29.2 The Two Traditions in Pharmacogenetics

449

(3)

29.2.1 The Pharmacokinetic Tradition

450

(1)

29.2.1.1 Inborn Errors of Metabolism

450

(1)

29.2.1.2 Pharmacogenetics of Drug Metabolism

450

(1)

29.2.1.3 The Special Case of the Cytochrome P450 Superfamily of Phase I Drug Metabolizing Enzymes

451

(1)

29.2.2 The Pharmacodynamic Tradition

451

(1)

29.2.3 Let Us Not Forget the Influence of the Environment

452

(1)

29.3 Single Genes and Pharmacogenetics

452

(1)

29.4 Pharmacogenetics and Complex Traits Analysis

453

(1)

29.5 QTL to QTGene

454

(1)

29.6 Pharmacogenomics—The Next Step

454

(1)

29.7 Summary

455

(1)

References

455

(2)

Chapter 30 Alcohol Psychopharmacogenetics

457

(12)

John C. Crabbe

30.1 Introduction

457

(1)

30.2 Animal Pharmacogenetic Studies

458

(4)

30.2.1 Studies with Inbred Strains

458

(1)

30.2.2 Studies with Selectively Bred Lines

459

(1)

30.2.3 Gene Identification and Targeting Studies

460

(2)

30.2.3.1 QTL Mapping Studies

460

(1)

30.2.3.2 Transgenic, Null Mutant, Antisense, and Other Gene-Targeted Expression Studies

461

(1)

30.3 Human Studies

462

(2)

30.3.1 Twin and Adoption Studies

462

(1)

30.3.2 Candidate Gene Studies

463

(1)

30.3.3 Identification of Risk Markers and QTLs

463

(1)

30.4 Gene Expression Analyses

464

(1)

30.5 Conclusions

464

(1)

Acknowledgments

464

(1)

References

464

(5)

Index

469

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