21 - High-throughput single nucleotide polymorphism genotyping

Summary

OVERVIEW

The completion of a draft of the human genome sequence provides unprecedented opportunities for the discovery of important, genetically validated targets in complex, polygenic diseases. The growing catalogs of single nucleotide polymorphisms (SNPs) are becoming the basic tool for use in genetic association studies to identify genes for many medically important conditions. Drug responses is as complex as disease genetics, resulting from underlying genotypic variation at many loci and also from variation in other nongenetic factors. Genomic technologies are increasingly being adopted in the biotechnology and pharmaceutical industries to accelerate identification of disease-validated targets for drug discovery. Improved genotyping methods combined with a large number of defined SNPs will lead to an increasing number of genetically validated targets. In this chapter, the major methodologies that have been developed over the past few years for SNP genotyping are described. Most of these methods have been directed to allowing high-throughput analysis of a large number of SNPs over a large number of samples, at a reduced cost. Using these technologies is likely to provide for a radical change in drug development, prescription and utilization.

Introduction

Complexity of the genetic component of the drug response

Drug response variation among individuals can have important implications and is a major concern for the clinician, as well as for the pharmaceutical industry. In some cases, this variation will affect the daily dosage (which can even vary up to 40-fold) for different individuals.