Genetic dissection of complex traits:
Gespeichert in:
Format: | Buch |
---|---|
Sprache: | English |
Veröffentlicht: |
San Diego [u.a.]
Acad. Press
2001
|
Schriftenreihe: | Advances in genetics
42 |
Schlagworte: | |
Online-Zugang: | Inhaltsverzeichnis |
Beschreibung: | Einzelaufnahme eines Zeitschr.-Bd. |
Beschreibung: | XXI, 583 S. graph. Darst. |
ISBN: | 0120176424 |
Internformat
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Datensatz im Suchindex
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adam_text | Contents
Contributors xv
Preface xix
Acknowledgments xxi
1 NEWTON MORTON S CONTRIBUTIONS
1 Newton Morton: The Wisconsin Years 3
James F. Crow
Newton Morton: The Wisconsin Years 3
References 5
2 Newton Morton s Influence on Genetics:
The Morton Number 7
Daniel E. Weeks
I. The Morton Number 7
II. Data 8
References 10
2 OVERVIEW AND PRELIMINARIES
3 Genetic Dissection of Complex Traits: An Overview 13
D. C. Rao
I. Summary 13
II. Introduction 14
III. Existence of Genetic Effects 17
IV. Overall Study Design 19
V. Other Issues Related to Study Design 23
VI. Lumping and Splitting as a Strategy 26
VII. Discussion 30
References 32
V
vi Contents
4 Familial Resemblance and Heritability 35
Treva K. Rice and Ingrid B. Borecki
I. Summary 35
II. Introduction 36
III. Familial Resemblance and Heritability 37
IV. Study Designs and Multifactorial Models 38
V. Discussion 42
References 43
5 Linkage and Association: Basic Concepts 45
Ingrid B. Borecki and Brian K. Suarez
I. Summary 45
II. Introduction 46
III. Historical Perspective 47
IV. Fundamentals and Methods 49
V. Contemporary Approaches 56
VI. Challenges and Issues 58
References 63
3 PHENOTYPES AND GENOTYPES
6 Definition of the Phenotype 69
John P. Rice, Nancy L. Saccone, and Erik Rasmussen
I. Summary 69
II. Introduction 70
III. The Benefits of a Narrowly Defined Disease Phenotype 70
IV. Endophenotypes and Quantitative Traits 71
V. The Impact of Diagnostic and Measurement Error 73
VI. Discussion 74
References 75
7 Genotyping for Human Whole Genome Scans:
Past, Present, and Future 77
James L. Weber and Karl W. Broman
I. Summary 77
II. Introduction: Genotyping Past 78
III. Genotyping Present 79
Contents vii
IV. Genotyping Future 90
V. Conclusions 94
References 94
4 MODEL BASED METHODS FOR LINKAGE ANALYSIS
8 The Lod Score Method 99
John P. Rice, Nancy L. Saccone, and Jonathan Corbett
I. Summary 99
II. Introduction 100
III. The Generalized Single Major Locus Model 100
IV. The Lod Score 101
V. The Lod Score and Meta analysis 104
VI. The Probability of Detecting Linkage 106
VII. Model free Linkage Methods 108
VIII. Discussion 112
References 112
9 Extension of the Lod Score: The Mod Score 115
Francoise Clerget Darpoux
I. Summary 115
II. Introduction 116
III. Misspecifying Genetic Parameters at the Disease Locus in Lod
Score Analysis 117
IV The Mod Score Function 119
V. Conclusion 122
References 123
10 Major Strengths and Weaknesses of the Lod Score
Method 125
Jurg Ott
I. Summary 125
II. Introduction 126
III. Genes Underlying Complex Traits 127
IV. Weaknesses of Lod Score Method 127
V Strengths of the Lod Score Method 129
References 131
viii Contents
5 MODEL FREE METHODS FOR LINKAGE AND
ASSOCIATION ANALYSIS
11 Overview of Model free Methods for Linkage Analysis 135
Robert C. Elston and Heather J. Cordell
I. Summary 135
II. Introduction 136
III. Estimating Marker Identity by Descent 136
IV. Quantitative Traits 138
V. Qualitative Traits 141
VI. Discussion 146
References 147
12 Variance Component Methods for Detecting Complex Trait
Loci 151
John Blangero, Jeff T. Williams, and Laura Almasy
I. Summary 151
II. Introduction 152
III. Variance Component Based Linkage Analysis 153
IV. The Effects of Nonnormality 159
V. Power of Variance Component Linkage Analysis 172
VI. Conclusions 178
References 179
13 Linkage and Association with Structural Relationships 183
Michael A. Province
I. Summary 183
II. Introduction 183
III. SEGPATH Linkage and Association Models 185
IV. Unique Features of SEGPATH Models 189
V. Discussion 190
References 190
14 The Future of Genetic Case Control Studies 191
Nicholas J. Schork, Dani Fallin, Bonnie Thiel, Xiping Xu,
Ulrich Broeckel, Howard J. Jacob, and Daniel Cohen
I. Summary 192
II. Introduction 192
Contents ix
III. Stratification 194
IV. Assessing Statistical Significance 196
V. Multiple Linked Loci and Haplotype Analysis 199
VI. Haplotype Diversity and Allelic Heterogeneity 200
VII. Genetic Background and Allelic Heterogeneity 201
VIII. Genetic Outlier Detection 204
IX. Genetic Matching 204
X. Assessing Power and Linkage Disequilibrium Strength 205
XL Assessing Admixture 205
XII. Pleiotropy and Physiologic Significance 206
XIII. Discussion 209
References 210
15 Cost of Linkage versus Association Methods 213
Christopher I. Amos and Grier Page
I. Summary 213
II. Introduction 214
III. Methods 215
IV Results 217
V Discussion 218
References 220
16 Genotype Environment Interaction in Transmission
Disequilibrium Tests 223
Lindon J. Eaves and Patrick Sullivan
I. Summary 224
II. Introduction 224
III. Model for Genetic and Environmental Risk 226
IV. Generalizing the Approach to Allow for G X E and Other
Interactions 228
V Evaluation of the Method through Simulation 229
VI. Conclusions and Discussions 238
References 240
17 Major Strengths and Weaknesses of Model free
Methods 241
David E. Goldgar
I. Summary 241
II. Introduction 242
x Contents
III. Nonparametric Methods in Statistics 244
IV. Do We Need Model free Methods? 244
V. Quantitative Traits 249
VI. Discussion 249
References 250
6 MORE RECENT METHODS
18 Meta analysis for Model free Methods 255
Chi Gu, Michael A. Province, and D. C. Rao
I. Summary 255
II. Introduction 256
III. Meta analysis of Genetic Studies 258
IV. Practical Issues 265
V. Discussion 267
References 271
19 Classification Methods for Confronting
Heterogeneity 273
Michael A. Province, W. D. Shannon, and D. C. Rao
I. Summary 273
II. Introduction 274
III. Coping with the Challenges 274
IV. Recursive Partitioning Models 277
V. Discussion 284
References 285
20 Applications of Neural Networks for Gene Finding 287
Andrea Sherriff and Jurg Ott
I. Summary 287
II. Introduction 288
III. Description of Artificial Neural Networks 288
IV. Interaction among Genes Underlying Complex Traits 291
V. Applications of Neural Networks to Genetic Data 292
VI. Discussion 295
References 296
Contents xi
21 Genome Partitioning and Whole Genome Analysis 299
Nicholas J. Schork
I. Summary 299
II. Introduction 300
III. The Basic Model 301
IV. WG and GP Analysis with Human Family Data 304
V. WG and GP Analysis with Inbred Model Organism
Crosses 310
VI. Human Population Based Studies 314
VII. Extensions to Basic MIVC Model 317
VIII. Discussion and Conclusion 318
References 319
22 Deciphering the Genetic Architecture of a Multivariate
Phenotype 323
Saurabh Ghosh and Partha P. Majumder
I. Summary 323
II. Introduction and Objective 324
III. Scenarios and Models 325
IV. Methodology 329
V. Results and Discussion 333
VI. Conclusions 346
References 347
7 OPTIMUM STRATEGIES
23 On the Resolution and Feasibility of Genome Scanning
Approaches 351
Joseph D. Terwilliger
I. Summary 352
II. Introduction 352
III. Mapping a Locus with Known Genotypes 353
IV. Mapping a Locus Influencing Some Phenotype (Genotypes
Uncertain) 362
V Allowing for Trait Locus Genotype Misclassifications 365
VI. Model Based and Model free Methods: A False
Dichotomy 374
xii Contents
VII. Complex Disease Gene Mapping: Is It Possible? 380
VIII. Conclusions 387
References 389
24 The Role of Interacting Determinants in the Localization of
Genes 393
W. James Gauderman and Duncan C. Thomas
I. Summary 393
II. Introduction 394
III. Penetrance Models Incorporating Interaction Effects 394
IV. Segregation Analysis 396
V. Linkage Analysis 398
VI. Association Studies 405
VII. Treatment of Missing Covariate Data 407
VIII. Conclusion 408
References 409
25 Linkage Disequilibrium Mapping: The Role of Population
History, Size, and Structure 413
N. H. Chapman and E. A. Thompson
I. Summary 413
II. Introduction 414
III. IBD and Allelic Associations at a Single Locus 415
IV. Allelic Associations between Two Loci 417
V. Estimation of © from Observed Associations 428
VI. Effects of Size and Structure on Allelic Associations 428
VII. Structure in Human Populations: Some Examples 431
References 434
26 Optimum Study Designs 439
Chi Gu and D. C. Rao
I. Summary 439
II. Introduction 440
III. Phenotyping and Genotyping Issues 441
IV. Sampling Issues 442
V. Sample Size and Power 446
VI. Cost Benefit Issues 451
VII. Discussions 454
References 456
Contents xiii
27. One Stage versus Two Stage Strategies for Genome
Scans 459
Xiuqing Guo and Robert C. Elston
I. Summary 460
II. Introduction 460
III. One Stage and Two Stage Procedures 461
IV. Two Stage Global Search Designs Using Discordant Relative
Pairs 461
V. Using Both Discordant and Affected Relative Pairs 464
VI. Effect of Genetic Heterogeneity and Incomplete Marker
Information 467
VII. The Computer Program DESPAIR 468
VIII. Discussion 469
References 470
8 MULTIPLE COMPARISONS AND SIGNIFICANCE
LEVELS
28. Significance Levels in Genome Scans 475
Glenys Thomson
I. Summary 475
II. Introduction 476
III. Approaches for Complex Diseases 477
IV. Genome Wide Linkage Scans in Complex Diseases 478
V. Genome Wide Association Scans in Complex Diseases 480
VI. Discussion 482
References 484
29. False Positives and False Negatives in Genome Scans
487
D. C. Rao and Chi Gu
I. Summary 487
II. Introduction 488
III. False Positives and False Negatives 488
IV. Trade off between False Positives and False Negatives 493
V. Discussion 496
References 497
xiv Contents
30 Sequential Methods of Analysis for Genome Scans 499
Michael A. Province
I. Summary 499
II. Introduction 500
III. Background and Significance 502
IV. Sequential Analysis Theory 505
V. Discussion 512
References 514
9 CHALLENGES FOR THE NEW MILLENNIUM
31 From Genetics to Mechanism of Disease Liability 517
Jean Marc Lalouel
I. Summary 517
II. Introduction 518
III. Statistical Inference 521
IV. Functional Significance at the Molecular Level 525
V. Mechanism at the Cellular and Organ Levels 529
VI. Analysis at the Level of the Whole Organism 530
VII. Evolutionary Implications 531
References 532
32 Complex Inheritance: The 21st Century 535
Newton E. Morton
I. Summary 535
II. Introduction 536
III. Mapping 536
IV. Positional Cloning 537
V. Pooling Evidence 538
VI. Fully Parametric Analysis 540
VII. Pessimistic and Optimistic Views of the 21st Century 541
References 542
Appendix: Research Contributions of Newton E. Morton 545
Index 569
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isbn | 0120176424 |
language | English |
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spelling | Genetic dissection of complex traits ed. by D. C. Rao ... San Diego [u.a.] Acad. Press 2001 XXI, 583 S. graph. Darst. txt rdacontent n rdamedia nc rdacarrier Advances in genetics 42 Einzelaufnahme eines Zeitschr.-Bd. Gen-Targeting (DE-588)4294998-1 gnd rswk-swf Gentransfer (DE-588)4194102-0 gnd rswk-swf Gentherapie (DE-588)4296957-8 gnd rswk-swf Methode (DE-588)4038971-6 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Bibliographie 1953-1999 - Morton, Newton E Kongress - Saint Louis <Mo, 1999> - Faktorenkopplung - Genanalyse Kongress - Saint Louis <Mo, 1999> - Genanalyse - Phänotyp Kongress - Saint Louis <Mo, 1999> - Methode - Faktorenkopplung - Modellwahl Gentherapie (DE-588)4296957-8 s DE-604 Gentransfer (DE-588)4194102-0 s Methode (DE-588)4038971-6 s Gen-Targeting (DE-588)4294998-1 s Rao, Dabeeru C. Sonstige oth Advances in genetics 42 (DE-604)BV000897065 42 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009209253&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
spellingShingle | Genetic dissection of complex traits Advances in genetics Gen-Targeting (DE-588)4294998-1 gnd Gentransfer (DE-588)4194102-0 gnd Gentherapie (DE-588)4296957-8 gnd Methode (DE-588)4038971-6 gnd |
subject_GND | (DE-588)4294998-1 (DE-588)4194102-0 (DE-588)4296957-8 (DE-588)4038971-6 (DE-588)4143413-4 |
title | Genetic dissection of complex traits |
title_auth | Genetic dissection of complex traits |
title_exact_search | Genetic dissection of complex traits |
title_full | Genetic dissection of complex traits ed. by D. C. Rao ... |
title_fullStr | Genetic dissection of complex traits ed. by D. C. Rao ... |
title_full_unstemmed | Genetic dissection of complex traits ed. by D. C. Rao ... |
title_short | Genetic dissection of complex traits |
title_sort | genetic dissection of complex traits |
topic | Gen-Targeting (DE-588)4294998-1 gnd Gentransfer (DE-588)4194102-0 gnd Gentherapie (DE-588)4296957-8 gnd Methode (DE-588)4038971-6 gnd |
topic_facet | Gen-Targeting Gentransfer Gentherapie Methode Aufsatzsammlung Bibliographie 1953-1999 - Morton, Newton E Kongress - Saint Louis <Mo, 1999> - Faktorenkopplung - Genanalyse Kongress - Saint Louis <Mo, 1999> - Genanalyse - Phänotyp Kongress - Saint Louis <Mo, 1999> - Methode - Faktorenkopplung - Modellwahl |
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