Genetic analysis of complex diseases /
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| Edition: | 2nd ed. |
|---|---|
| Imprint: | Hoboken, N.J. : Wiley-Liss, c2006. |
| Description: | xx, 485 p. : ill. ; 24 cm. |
| Language: | English |
| Subject: | |
| Format: | Print Book |
| URL for this record: | http://pi.lib.uchicago.edu/1001/cat/bib/6097471 |
Table of Contents:
- Foreword
- Preface
- Contributors
- 1. Basic Concepts in Genetics and Linkage Analysis
- Introduction
- Historical Contributions
- Segregation and Linkage Analysis
- Hardy-Weinberg Equilibrium
- DNA, Genes, and Chromosomes
- Structure of DNA
- Genes and Alleles
- Genes and Chromosomes
- Inheritance Patterns in Mendelian Disease
- Genetic Changes Associated with Disease/Trait Phenotypes
- Point Mutations
- Deletion/Insertion Mutations
- Novel Mechanisms of Mutation: Unstable DNA and Trinucleotide Repeats
- Susceptibility Versus Causative Genes
- Genes, Mitosis, and Meiosis
- When Genes and Chromosomes Segregate Abnormally
- Ordering and Spacing of Loci by Mapping Techniques
- Physical Mapping
- Genetic Mapping
- Interference and Genetic Mapping
- Meiotic Breakpoint Mapping
- Disease Gene Discovery
- Information Content in a Pedigree
- Disease Gene Localization
- Extensions to Complex Disease
- Summary
- References
- 2. Defining Disease Phenotypes
- Introduction
- Exceptions to Traditional Mendelian Inheritance Patterns
- Pseudodominant Transmission of a Recessive
- Pseudorecessive Transmission of a Dominant
- Mosaicism
- Mitochondrial Inheritance
- Incomplete Penetrance and Variable Expressivity
- Genomic Imprinting
- Phenocopies and Other Environmentally Related Effects
- Heterogeneity
- Genetic Heterogeneity
- Phenotypic Heterogeneity
- Complex Inheritance
- Polygenic and Multifactorial Models
- Role of Environment
- Role of Chance in Phenotype Expression
- Phenotype Definition
- Classification of Disease
- Nonsyndromic Phenotypes
- Syndromic Phenotypes
- Associations and Syndromes of Unknown Cause
- Importance of Chromosomal Rearrangements in Mapping
- Qualitative (Discontinuous) and Quantitative (Continuous) Traits
- Defining Phenotypes for Analysis of Complex Genetic Disorders
- Select Most Biologically Meaningful Phenotype
- Partition Phenotype or Dataset by Cause and Associated Pathology
- Summary: Approach to Phenotype Definition
- Resources for Information about Clinical Genetics and Phenotype Definition
- References
- 3. Determining Genetic Component of a Disease
- Introduction
- Study Design
- Selecting a Study Population
- Ascertainment
- Approaches to Determining the Genetic Component of a Disease
- Cosegregation with Chromosomal Abnormalities and Other Genetic Disorders
- Familial Aggregation
- Twin and Adoption Studies
- Recurrence Risk in Relatives of Affected Individuals
- Heritability
- Segregation Analysis
- Summary
- References
- 4. Patient and Family Participation in Genetic Research Studies
- Introduction
- Step 1. Preparing to Initiate a Family Study
- Confidentiality
- Certificate of Confidentiality
- Need for a Family Studies Director
- Working with Human Subjects
- Step 2. Ascertainment of Families for Studies
- Family Recruitment
- Informed Consent and Family Participation
- Step 3. Data Collection
- Confirmation of Diagnosis
- Art of Field Studies
- Special Issues in Family Studies
- Step 4. Family Follow-Up
- Need for Additional Medical Services
- Duty to Recontact Research Participants
- Maintaining Contact with Participants
- Guidelines for Releasing Genetic Information
- Genetic Testing of Children
- Genetic Discrimination
- DNA Banking
- Future Considerations
- Appendix
- References
- 5. Collection of Biological Samples for DNA Analysis
- Establishing Goals of Collection
- Types of DNA Sample Collection
- Venipuncture (Blood)
- Buccal Samples
- Dried Blood
- Tissue
- DNA Extraction and Processing
- Blood
- Quantitation
- Tissue Culture
- Buccal Brushes
- Dried Blood Cards
- Fixed Tissue
- Whole-Genome Amplification
- Sample Management
- Informed Consent/Security
- References
- 6. Methods of Genotyping
- Brief Historical Review of Markers Used for Genotyping
- Restriction Fragment Length Polymorphisms
- Variable Number of Tandem Repeat Markers
- Short Tandem Repeats or Microsatellites
- Single-Nucleotide Polymorphisms
- Sources of Markers
- Restriction Fragment Length Polymorphisms
- Microsatellites
- Single-Nucleotide Polymorphisms
- PCR and Genotyping
- Laboratory and Methodology Optimization
- Optimization of Reagents
- "I Can't Read a Marker, What Should I Do?"
- Marker Separation
- Manual or Nonsequencer Genotyping
- Loading Variants
- DNA Pooling and Homozygosity Mapping
- Detection Methods
- Radioactive Methods ([superscript 32]P or [superscript 33]P)
- Silver Stain
- Fluorescence
- SNP Detection
- DNA Array or "Chip"
- Oligonucleotide Ligation Assay
- Fluorescent Polarization
- Taqman
- Single-Base-Pair Extension
- Pyrosequencing
- Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Spectrometry
- Invader and PCR-Invader Assays
- Single-Strand Conformational Polymorphism
- Denaturing High-Pressure Liquid Chromatography
- Data Management
- Objectivity
- Genotype Integrity
- Scoring
- Standards
- Quality Control
- References
- 7. Data Analysis Issues in Expression Profiling
- Introduction
- Serial Analysis of Gene Expression
- Analysis of SAGE Libraries
- Microarray Analysis
- Data Preparation
- Expression Data Matrix
- Dimension Reduction of Features
- Measures of Similarity between Objects
- Unsupervised Machine Learning: Clustering
- Supervised Machine Learning
- Data Visualization
- Other Types of Gene Expression Data Analysis
- Biological Applications of Expression Profiling
- References
- 8. Information Management
- Information Planning
- Needs Assessment
- Information Flow
- Plan Logical Database Model
- Hardware and Software Requirements
- Software Selection
- System Administration
- Database Administration
- Database Implementation
- Conversion
- Performance Tuning
- Data Integrity
- User Interfaces
- Security
- Transmission Security
- System Security
- Patient Confidentiality
- Pedigree Plotting and Data Manipulation Software
- Summary
- 9. Quantitative Trait Linkage Analysis
- Introduction to Quantitative Traits
- Genetic Architecture
- Study Design
- Haseman-Elston Regression
- Multipoint IBD Method
- Variance Component Linkage Analysis
- Nonparametric Methods
- Future Directions
- Summary
- References
- 10. Advanced Parametric Linkage Analysis
- Two-Point Analysis
- Example of LOD Score Calculation and Interpretation
- Effects of Misspecified Model Parameters in LOD Score Analysis
- Impact of Misspecified Disease Allele Frequency
- Impact of Misspecified Mode of Inheritance
- Impact of Misspecified Disease Penetrances
- Impact of Misspecified Marker Allele Frequency
- Control of Scoring Errors
- Genetic Heterogeneity
- Multipoint Analysis
- Practical Approaches for Model-Based Linkage Analysis of Complex Traits
- Affecteds-Only Analysis
- Maximized Maximum LOD Score
- Heterogeneity LOD
- MFLINK
- Summary
- References
- 11. Nonparametric Linkage Analysis
- Introduction
- Background and Historical Framework
- Identity by State and Identity by Descent
- Measures of Familiality
- Qualitative Traits
- Measuring Genetic Effects in Quantitative Traits
- Summary of Basic Concepts
- Methods for Nonparametric Linkage Analysis
- Tests for Linkage Using Affected Sibling Pairs (ASPs)
- Methods Incorporating Affected Relative Pairs
- Power Analysis and Experimental Design Considerations for Qualitative Traits
- Nonparametric Quantitative Trait Linkage Analysis
- Power and Sampling Considerations for Mapping Quantitative Trait Loci
- Examples of Application of Sibpair Methods for Mapping Complex Traits
- Additional Considerations in Nonparametric Linkage Analysis
- WPC Analysis
- Software Available for Nonparametric Linkage Analysis
- Summary
- References
- 12. Linkage Disequilibrium and Association Analysis
- Introduction
- Linkage Disequilibrium
- Measures of Allelic Association
- Causes of Allelic Association
- Mapping Genes Using Linkage Disequilibrium
- Tests for Association
- Case-Control Tests
- Family-Based Tests of Association
- Analysis of Haplotype Data
- Association Tests for Quantitative Traits
- Association and Genomic Screening
- Special Populations
- Summary
- References
- 13. Sample Size and Power
- Introduction
- Power Studies for Linkage Analysis: Mendelian Disease
- Information Content of Pedigrees
- Computer Simulation Methods
- Definitions for Power Assessments
- Power Studies for Linkage Analysis: Complex Disease
- Discrete Traits
- Quantitative Traits
- Power Studies for Association Analysis
- Transmission/Disequilibrium Test for Discrete Traits
- Transmission/Disequilibrium Test for Quantitative Traits
- Case-Control Study Design
- DNA Pooling
- Genomic Screening Strategies for Association Studies
- Simulation of Linkage and Association Program
- Summary
- Appendix 13.1. Example of Monte Carlo Simulation Assuming That Trait and Marker Loci Are Unlinked to Each Other
- Appendix 13.2. Example LOD Score Results for Pedigree in Figure 13.2
- Appendix 13.3. Example of Simulation of Genetic Marker Genotypes Conditional on Trait Phenotypes Allowing for Complete and Reduced Penetrance
- References
- 14. Complex Genetic Interactions
- Introduction
- Evidence for Complex Genetic Interactions Genetic Heterogeneity
- Genetic Heterogeneity
- Gene-Gene Interaction (Epistasis)
- Gene-Environment Interaction
- Analytic Approaches to Detection of Complex Interactions
- Segregation Analysis
- Linkage Analysis
- Association Analysis
- Potential Biases
- Conclusion
- References
- 15. Genomics and Bioinformatics
- Introduction
- Era of the Genome
- Mapping the Human Genome
- Genetic Mapping
- Radiation Hybrid Mapping
- Physical Mapping
- Public Data Repositories and Genome Browsers
- Single-Nucleotide Polymorphisms
- SNP Discovery
- Utilizing SNPs
- Computational SNP Resources
- Model Organisms
- Identifying Candidate Genes by Genomic Convergence
- De Novo Annotation of Genes
- Software Suites
- Online Sequence Analysis Resources
- Understanding Molecular Mechanisms of Disease
- Assigning Gene Function
- Looking Beyond Genome Sequence
- Other Databases
- Summary
- References
- 16. Designing a Study for Identifying. Genes in Complex Traits
- Introduction
- Components of a Disease Gene Discovery Study
- Define Phenotype
- Develop Study Design
- Analysis
- Follow-Up
- Keys to a Successful Study
- Foster Interaction of Necessary Expertise
- Develop Careful Study Design
- References
- Index
