Chapter 2. Applications of Genomics in Clinical Trials and Medicine
2.1. Prediction, Detection, and Diagnosis of Disease
2.2. Predicting Response to Drugs
Historical Perspective
Pharmacogenomics
2.3. Factors Influencing Response to Drugs
Drug Metabolism
-Pharmacogenomics of Phase I Drug Metabolism
-Pharmacogenetics of Phase II Drug Metabolism: N-Acetyltransferase
-Pharmacogenetics of Phase II Drug Metabolism: Thiopurine S-Methyltransferase
Drug Transporters
Genetic Polymorphism of Drug Targets
Genetic Variants with Indirect Effects on Drug Response
2.4. Personalized Medicine
Variation in Gene Expression
Cancer Classification, Diagnosis, and Prognosis
-Cancer Classification
-Cancer Diagnosis
Sidebar: Cancer Genome Anatomy Project
-Cancer Prognosis
2.5. Toxicogenomics
2.6. Determining Risk of Disease
Inherited Genetic Variation
Sidebar: Categories of Inherited DNA Diseases
Single-Gene Genetic Disorders
-Monogenic Trait Example: Cystic Fibrosis
Multifactorial Disorders
-Multifactorial Disease Example #1: Alzheimer’s Disease
-Multifactorial Disease Example #2: Cancer
Sidebar: Genetic Origin of Cancers
Screening Newborns
2.7. Gene Therapy
2.8. Identifying Individuals
Paternity Testing
Forensics
Identifying Remains
2.9. Proteomics

Chapter 3. Genomic Technologies for the Clinic
3.1. Overview
3.2. Detecting DNA Variation
Single Nucleotide Polymorphisms
Haplotypes
-HapMap Project
-Selected Companies Active in Haplotypes
3.3. SNP Genotyping Methods
Sidebar: SNP Detection
Evaluating SNP Technologies for Clinical Applications
-Cost of SNP Genotyping
-Success Rates
-Accuracy
Throughput Considerations
Selected Companies Active in SNP Genotyping
-Sequenom
-Illumina
-Affymetrix
-PerkinElmer
-Third Wave Technologies
-Applied Biosystems Group
-Beckman Coulter
3.4. Gene Expression Detection
Methods for Measuring Gene Expression
-DNA Microarrays
-DNA Synthesis
-DNA Deposition
Box Feature: Gene Expression Database
Computational Issues
Evaluating the Technologies
Cross-Platform Comparisons
Selected Companies Marketing Gene Expression Microarrays
-Affymetrix
-Agilent Technologies
-Applied Biosystems
-CombiMatrix
-Brinkmann Instruments
3.5. RNA Interference
Selected Companies Active in RNAi Therapy
-Alnylam Pharmaceuticals
-Sirna Therapeutics
-Acuity Pharmaceuticals
3.6. Other Technologies
Epigenetic Markers
-Sequenom’s Approach
-Epigenomics’ DNA Methylation Technique
Alternative Splicing
Proteomics

Chapter 4. Advances in Clinical Genomics Applications
4.1. Overview
4.2. Toxicogenomics
Adoption of Clinical Toxicogenomics Tests
Case Study #1: First Microarray Approved for Treatment Decisions
Sidebar: P450 Drug Interaction Card
Case Study #2: First Pharmacogenetic Test Approved As Companion to Therapy
Case Study #3: TPMT
4.3. Clinical Trials
4.4. Clinical Oncology
Case Study #1: Cancer Gene Expression
-Agendia’s MammaPrint Gene Expression Assay
-Genomic Health’s Oncotype DX
Case Study #2: Genentech’s Herceptin and Her-2
Case Study #3: BRCA1 and BRCA2 Genes and Myriad Genetics
Box Feature 4.1: Human Cancer Genome Project
4.5. Infectious Diseases
Case Study: HIV and AIDS
Other Applications for Genomics to Infectious Diseases
4.6. Newborn Screening
4.7. Genomics and Race
BiDil: The First Race-Based Drug
4.8. Genomics and Drug Labeling

Chapter 5. Business and Strategic Factors
5.1. Overview
5.2. Patient Stratification
Impact on Clinical Trials
Impact on the Market
5.3. Scientific Issues
Can Clinical Genomics Deliver on Its Promise?
Can the Influence of Genes on Drug Response Be Quantified?
5.4. Standardization and Quality Control
5.5. Physician and Payer Response
5.6. Drug-Diagnostic Codevelopment: Theranostics
5.7. The Regulatory Environment
FDA Guidelines on Pharmacogenomics
"Home-Brew" Testing, In Vitro Diagnostics, and the FDA
5.8. Cost-Benefit Analysis
Evaluating the Cost of Clinical Genomics
Factors Influencing Costs
Comparing Genomics With Other Testing and Treatment Options
Noteworthy Indications
5.9. Niche Markets for Clinical Genomics
Opportunity in Rare Diseases
Outlook for Toxicogenomics
Projected RNAi Market

Chapter 6. Expert Interviews
Edward Abrahams, PhD, Executive Director, Personalized Medicine Coalition (PMC)
Charles R. Cantor, PhD, Chief Scientific Officer SEQUENOM
Mickie Henshall, Product Manager, Molecular Diagnostics, Illumina, Inc.
William Craumer, Director, Corporate and Marketing Communications, Illumina, Inc.
Mark A. McCamish, MD, PhD, Chief Medical Officer, Perlegen Sciences

Chapter 7. Selected Company Profiles
Affymetrix
Agendia
Alnylam Pharmaceuticals
Applied Biosystems Group (ABI)
Agilent
Beckman Coulter, Inc.
Brinkmann Instruments (A Member of the Eppendorf Group)
CombiMatrix Corporation
DnaPrint Genomics Inc.
Encode (Subsidiary of deCODE)6
Epigenomics AG
ExonHit Therapeutics
Genaissance Pharmaceuticals
Gene Logic
Genomic Health
Genpathway Inc.
Gentris
Iconix Pharmaceuticals, Inc.
Illumina
Invitrogen
Myriad Genetics
Nanogen
NitroMed, Inc.
PathWork Informatics
Perlegen Sciences
PTC Therapeutics, Inc.
Roche Molecular Diagnostics
SEQUENOM, Inc.
Sirna Therapeutics
Third Wave Technologies, Inc.
Vanda Pharmaceuticals

References

Index