The Population Reference Sample, POPRES: a resource for population, disease, and pharmacological genetics research.

Technological and scientific advances, stemming in large part from the Human Genome and HapMap projects, have made large-scale, genome-wide investigations feasible and cost effective. These advances have the potential to dramatically impact drug discovery and development by identifying genetic factors that contribute to variation in disease risk as well as drug pharmacokinetics, treatment efficacy, and adverse drug reactions. In spite of the technological advancements, successful application in biomedical research would be limited without access to suitable sample collections.

Pharmacogenetics to predict drug-related adverse events.

Identification of reliable markers to predict drug-related adverse events (DRAEs) is an important goal of the pharmaceutical industry and others within the healthcare community. We have used genetic polymorphisms, including the most frequent source of variation (single nucleotide polymorphisms, SNPs) in the human genome, in pharmacogenetic approaches designed to predict DRAEs. Three studies exemplify the principles of using polymorphisms to identify associations in progressively larger genomic regions: polymorphic repeats within the UDP-glucuronysltransferase I (UGT1A1) gene in patients experiencing hyperbilirubinemia after administration of tranilast, an experimental drug to prevent re-stenosis following coronary revascularization; high linkage disequilibrium within the Apolipoprotein E (ApoE) gene in patients with Alzheimer Disease (AD); and the polymorphic variant HLA-B57 in patients with hypersensitivity reaction after administration of abacavir, a nucleoside reverse transcriptase inhibitor for the treatment of HIV.

Association of genetic variations in HLA-B region with hypersensitivity to abacavir in some, but not all, populations.

Abacavir is an effective antiretroviral drug used to treat HIV-1 infection. Approximately 5% of patients treated with abacavir develop a hypersensitivity reaction that requires discontinuation of the drug. In an initial pharmacogenetic study conducted in a predominantly White male population, multiple markers in the human leukocyte antigen (HLA)-B chromosomal region were associated with hypersensitivity to abacavir.

Multiplexed SNP genotyping using the Qbead system: a quantum dot-encoded microsphere-based assay.

We have developed a new method using the Qbead system for high-throughput genotyping of single nucleotide polymorphisms (SNPs). The Qbead system employs fluorescent Qdot semiconductor nanocrystals, also known as quantum dots, to encode microspheres that subsequently can be used as a platform for multiplexed assays. By combining mixtures of quantum dots with distinct emission wavelengths and intensities, unique spectral 'barcodes' are created that enable the high levels of multiplexing required for complex genetic analyses.