Genetics of Asthma And Chronic Obstructive Pulmonary Disease

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ISBN: 9780849369667 | 0849369665
Cover: Hardcover
Copyright: 9/6/2006

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Responding to the substantial growth that has taken place in the field over the past decade, this reference provides an in-depth overview of current thought on the genetics and genomics of asthma and COPD in relation to their pathogenesis and treatment. With contributions by an esteemed team of international authorities on the topic, this source spans the latest developments in the utilization of microarray techniques, linkage and association studies, mapping strategies, comparative genetics, microarray techniques, proteomics, and pharmacogenomics.

Introduction

Claude Lenfant

Preface

vii

Contributors

1. Introduction to Genetics

(16)

Eva Halapi and Hakon Hakonarson

I. Introduction

(1)

II. Mendelian Traits vs. Complex Diseases

(2)

III. Familial Risk and Heritability

(2)

IV. Linkage Disequilibrium

(1)

V. Genetic Linkage Analysis

(4)

VI. Genetic Architecture of Complex Diseases

(1)

VII. Gene-by-Gene and Gene-by-Environment Interactions

(1)

VIII. Genetic Association Studies

(1)

References

(4)

2. Genetic Epidemiology of Reduced Lung Function

(16)

Cleo C. van Diemen and H. Marike Boezen

I. Introduction

(1)

II. Environmental and Genetic Factors Affecting Lung Function

(1)

III. Family and Twin Studies

(1)

IV. Segregation Analysis and Heritability

(1)

V. Genome-Wide Linkage Analysis

(4)

VI. Case–Control Studies

(1)

VII. Population-Based Longitudinal Studies on Decline in Lung Function

(1)

VIII. Genetically Isolated Populations

(1)

IX. Conclusion

(1)

References

(5)

3. Gene–Environment Interaction in Asthma

(22)

Gerard H. Koppelman and Dirkje S. Postma

I. Introduction

(1)

II. Evidence for Gene–Environment Interaction in Asthma

(2)

III. Concept, Definition, and Methods

(2)

IV. Family Studies

(1)

V. Candidate Gene Studies

(10)

VI. Summary and Future Prospects

(1)

References

(6)

4. Epistatic Interaction, Age, and Gender Effects

(20)

Michael Kabesch

I. Introduction

(1)

II. Multiple Genes Involved in Disease Occurrence and Perpetuation

(1)

III. A Three-Dimensional Model of Disease Complexity

(1)

IV. Complex Challenges and Complex Developments

(1)

V. Does Gene-by-Gene Interaction Really Exist?

(2)

VI. Genes of the IL-4/IL-13 Signalling Pathway

(2)

VII. How to Assess Gene-by-Gene Interactions?

(3)

VIII. Evidence for Gene-by-Gene Interactions in the IL-4/IL-13 Pathway

(2)

IX. From Epistasis to Gender and Age

(2)

X. Are We There Yet?

(1)

References

(5)

5. Microarray Techniques and Data in Asthma/Chronic Obstructive Pulmonary Disease

(30)

Thomas J. Mariani and Marco F. Ramoni

I. Introduction

(2)

II. Basics of Microarray Technology

(3)

III. Microarray Data Processing

(3)

IV. Microarray Data Analysis

(6)

V. Application of Microarrays to Asthma Research

(4)

VI. Application of Microarrays to COPD Research

(2)

VII. Challenges and Opportunities for Future Applications

(3)

References

(7)

6. Mouse Models for Asthma and Mouse Asthma Genetics

105

(22)

Benoit Piavaux, Antoon J.M. van Oosterout, and Machteld N. Hylkema

I. Introduction

105

(1)

II. Mouse Models for Asthma

106

(4)

III. Mouse Asthma Genetics

110

(9)

IV. Concluding Remarks

119

(2)

References

121

(6)

7. Generation of Genetically Manipulated Mouse Lines for the Study of Asthma

127

(32)

Stephen L. Tilley, Irving C. Allen, and Beverly H. Koller

I. Introduction

127

(1)

II. Allergic Lung Disease in Mice

128

(1)

III. Phenotyping Methods and Principles

128

(4)

IV. Inflammatory Response

132

(2)

V. Manipulating the Mouse Genome

134

(21)

VI. Future Directions

155

(1)

References

156

(3)

8. Comparative Genomics of Asthma

159

(20)

Ioannis M. Stylianou, Jaspal Singh, David A. Schwartz, and Beverly Paigen

I. Introduction

159

(1)

II. Concordance of Quantitative Trait Loci Across Species

160

(1)

III. Asthma Quantitative Trait Loci in Humans and the Mouse

160

(8)

IV. Comparative Genomics

168

(3)

V. Steps that Would Enhance Asthma Research

171

(2)

VI. Concluding Remarks

173

(1)

References

174

(5)

9. Proteomic Techniques for Asthma and Chronic Obstructive Pulmonary Disease Research

179

(20)

Megan S. Lim and Kojo S.J. Elenitoba-Johnson

I. Introduction

179

(1)

II. Tools for Proteomics

180

(3)

III. Application of Proteomic Techniques to the Study of Asthma and COPD

183

(10)

IV. Summary

193

(1)

References

193

(6)

10. Linkage to Asthma and Its Intermediate Phenotypes

199

(12)

Timothy D. Howard and Juan C. Celedón

I. Introduction

199

(1)

II. Common Approaches to Genetic Studies of Asthma

200

(1)

III. Phenotypic Definition of Asthma

201

(1)

IV. Genome-Wide Linkage Analyses of Asthma and Its Intermediate Phenotypes

202

(5)

V. Summary

207

(1)

VI. Conclusions

208

(1)

References

208

(3)

11. Linkage Analysis of Spirometric Phenotypes and Chronic Obstructive Pulmonary Disease

211

(12)

Dawn L. Demeo, Craig P. Hersh, and Edwin K. Silverman

I. Linkage Analysis: General Description

211

(1)

II. Heritability of Spirometric Phenotypes in the General Population

212

(1)

III. Linkage Analysis of Pulmonary Function

213

(3)

IV. Linkage Analysis in COPD Families

216

(4)

References

220

(3)

12. Fine Mapping and Whole Genome Association Studies in Asthma and Chronic Obstructive Pulmonary Disease

223

(16)

Miriam F Moffatt and William O.C. Cookson

I. Introduction

223

(1)

II. Linkage Studies in Asthma and Chronic Obstructive Pulmonary Disease

224

(1)

III. Linkage Disequilibrium Mapping

224

(3)

IV. Gene Identification

227

(2)

V. Whole Genome Association Mapping

229

(3)

VI. Expression Quantitative Trait Loci

232

(1)

VII. Conclusions

233

(1)

References

233

(6)

13. Association Studies in Asthma

239

(34)

Ingrid A. Laing and Peter N. Le Souëf

I. Introduction

239

(2)

II. Selection of an Asthma Candidate Gene

241

(1)

III. Identification of Polymorphisms

241

(1)

IV. Selection of Polymorphisms for Association Studies

242

(1)

V. Population Selection/Study Design

242

(2)

VI. Methods Used to Identify New Asthma Candidate Genes

244

(1)

VII. Environmental Exposures

244

(1)

VIII. Association Study Limitations

245

(3)

IX. Association Study Interpretation

248

(1)

X. How to Establish an Asthma Gene

248

(2)

XI. Asthma Associations Reported

250

(10)

XII. Conclusions

260

(1)

References

261

(12)

14. Association Studies in Chronic Obstructive Pulmonary Disease

273

(26)

Takeo Ishii and Andrew J. Sandford

I. Introduction

273

(2)

II. Association Studies of Candidate Genes

275

(15)

III. Future Directions of Association Studies in COPD

290

(1)

References

291

(8)

15. β2-Adrenergic Receptor Polymorphisms and Asthmatic Phenotypes

299

(18)

Stephen B. Liggett and Ian P. Hall

I. Introduction

299

(1)

II. β2-AR Localization, Structure, and Function

300

(2)

III. Genetic Variation of the Human β2-AR

302

(5)

IV. Clinical Studies of β2-AR Variants in Asthma

307

(6)

V. Limitations of Current Studies and Future Directions

313

(1)

References

313

(4)

16. Interleukin-13

317

(16)

Donata Vercelli

I. Introduction

317

(1)

II. IL-13: The Central Mediator of Allergic Lung Inflammation

318

(2)

III. IL-13 Regulation in Early Life

320

(1)

IV. IL-13 Association Studies

321

(1)

V. A Corollary: IL-13 and Chronic Obstructive Pulmonary Disease

322

(1)

VI. IL-13+2044GA: Functional Studies

323

(1)

VII. Conclusions

324

(2)

References

326

(7)

17. CD14 and Toll-Like Receptors

333

(24)

Stefano Guerra and Fernando D. Martinez

I. Introduction

333

(1)

II. Biology and Genetic Variation of CD14 and Toll-Like Receptors

334

(4)

III. Marginal and Interactive Effects of CD14 Genetic Variation on Atopic Phenotypes

338

(4)

IV. The Relation of Microbial Exposure to Asthma and Chronic Obstructive Pulmonary Disease

342

(2)

V. Genetic Variation in Toll-Like Receptors and Asthma

344

(1)

VI. CD14/TLR4 Genetic Variation and Chronic Obstructive Pulmonary Disease

345

(2)

VII. Conclusions

347

(1)

References

348

(9)

18. Pharmacogenetics

357

(42)

Kelan Tantisira and Eugene Bleecker

I. Overview of Pharmacogenetics

357

(3)

II. The Pharmacogenetics of Asthma

360

(18)

III. The Pharmacogenetics of COPD

378

(8)

IV. Conclusion

386

(1)

References

386

(13)

Index

399

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Genetics of Asthma And Chronic Obstructive Pulmonary Disease

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