Vol. 29, Issue 4, 586-590, April 2001

Utilization of New Technologies in Drug Trials and Discovery

Maureen T. Cronin, Mylan Pho, Debjani Dutta, Felix Frueh, Leslie Schwarcz, and Thomas Brennan

ACLARA BioSciences, Inc., Mountain View, California (M.T.C., M.P.); and Protogene Laboratories, Inc., Menlo Park, California (D.D., F.F., L.S., T.B.)

It has become widely accepted that individual genetic variation is a prime determinant in both disease susceptibility and toxic response to therapeutic agents and xenobiotics. Emerging genetic sequence data and phenotype association studies are expected to enable disease risk prediction and guide subsequent therapeutic approaches in individual cases. However, making a good match between an individual genetic profile, disease risk prediction, and appropriate therapeutic intervention will require genotyping many polymorphic sites in large numbers of genes or single nucleotide polymorphism sites throughout the genome. Additionally, each polymorphism will have to be associated with a phenotype. Presumably, a composite phenotype may be predicted by integrating anticipated contributions from each polymorphism contributing to the complex genotype. Methods for executing such large-scale genotyping studies are rapidly evolving and becoming available. DNA microarray technology applied in hybridization-based genotyping assays is particularly well suited to respond to the accelerating pace of polymorphism discovery and the associated demand for highly parallel genotyping capability.