Introduction: The Value of SNPs
The realization that SNPs are plentiful and
potentially powerful markers of disease genes has led to exponential growth in
the number of companies seeking to use SNPs for drug and diagnostic discovery
and development. This phenomenon has, in turn, sparked the development of
exciting new tools for finding, mapping, and determining the utility of SNPs.
Still, much remains to be proven in this field.
Background: Racing to Map and Acquire SNPs
While many researchers believe that the most
common SNPs, and particularly those in coding regions, will be the most
valuable, others believe that anonymous SNPs will also be important.Two major
types of studies—the candidate gene approach and random
genome-wide association studies—are being
pursued to find valuable SNPs.
2.1 Why SNPs?
2.2 What Are SNPs?
2.3 Types of SNPs
2.4 Applications to Statistical
Studying Single-Gene Diseases: Linkage Analysis and Positional Cloning
Studying Complex Diseases: Association Studies
2.6 How Are SNPs Studied?
Creating a SNP Map—SNP Discovery
Determining Which SNPs Are Useful
Random Genome-wide Approach
Candidate Gene Approach
Major Hurdles: Statistical Issues
and Managing Costs
Access to Special Populations
Current and Emerging Technologies: Tremendous Demand for New Tools
Keen demand exists for tools that can provide
a quick and accurate means for running many genotypes, in many patients, at a
reasonable cost. While sequencing remains the mainstay for validation, the
future will include advances in microarrays, alternative amplification methods
to PCR, and increased use of mass spectrometry for SNP detection.
3.1 SNP Discovery Approaches
Primarily Sequencing-Based Approaches
Biochemical Variance Detection
3.2 Challenges In Scoring: Aiming
To Multiplex And Avoid PCR
Amplifying Sequence: Alternatives To PCR
Arraying SNPs: Expanding Formats
Hybridization, Primer Extension and Ligation
Applications: Preparing for the Age of Patient-Tailored Therapies
While many companies are hoping to use SNPs
to validate targets for drug and diagnostic discovery, the greatest interest in
SNPs revolves around their use to identify patients with positive or negative
responses to a particular drug—part of pharmacogenomics. Developments in this
field have the potential to reshape the pharmaceutical industry.
4.2 Additional Applications:
Discovery, Prognosis, Gene Function Analysis, and
Testing and Study Design
Business and Strategic Considerations: Advancing Technology or
on Particular Applications
Affymetrix and PE Corp. are the current
technological leaders, but many companies are vying for the SNP discovery and
genotyping markets. In the applications realm, those who have amassed the
largest numbers of SNPs, such as Genset and Variagenics, and those with the
best alliances, such as the deCode/Hoffman-La Roche deal, are in the best
position to succeed.
5.1 Industry Leaders
6. Outlook: Entering the Age of Applications
Within the next couple of years the vast
majority of SNPs of importance will already have been mapped. The next phase of
this race will be to establish and exploit correlations.
It is only through many relatively
large-scale studies that the critical answers about which SNPs are the most
useful and how they should be applied will be arrived at.
6.1 The Prospects for SNP-Based
6.2 Major Hurdles
Social and Ethical Considerations
Validating the Field
6.3 Commentaries from Editorial
Advisory Board Members
Appendix A: Company/Technology Profiles