Single Nucleotide Polymorphisms: Commercial and Scientific Prospects


1. 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.


2. Scientific 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 Analysis

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

Regional Scanning

Candidate Gene Approach


Major Hurdles: Statistical Issues and Managing Costs

Access to Special Populations

Population Factors



3. The 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

Mass Spectrometry


4. 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.

4.1 Pharmacogenomics/Pharmacogenetics

4.2 Additional Applications: Discovery, Prognosis, Gene Function Analysis, and

      Homogeneity Testing and Study Design


5. Business and Strategic Considerations: Advancing Technology or

Betting 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

Technology Leaders

Database Developers

Applications 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 Approaches

6.2 Major Hurdles

Social and Ethical Considerations

Patent Problems

Cost Considerations

Validating the Field

6.3 Commentaries from Editorial Advisory Board Members


Appendix A: Company/Technology Profiles


Company Index