High Throughput Genotyping Technologies for Pharmacogenomics

Abstract

Genetic differences between individuals play a role in determining susceptibility to diseases as well as in drug response. The challenge today is first to discover the range of genetic variability in the human population and then to define the particular gene variants, or alleles, that contribute to clinically important outcomes. Consequently, high throughput, automated methods are being developed that allow rapid scoring of microsatellite alleles and single nucleotide polymorphisms (SNPs). Many detection technologies are being used to accomplish this goal, including electrophoresis, standard fluorescence, fluorescence polarization, fluorescence resonance energy transfer, and mass spectrometry. SNP alleles may be distinguished by any one of several methods, including single nucleotide primer extension, allele-specific hybridization, allele-specific primer extension, oligonucleotide ligation assay, and invasive signal amplification. Newer methods require less sample manipulation, increase sensitivity, allow more flexibility, and decrease reagent costs. Recent developments show promise for continuing these trends by combining amplification and detection steps and providing flexible, miniaturized platforms for genotyping.

A genotyping system capable of simultaneously analyzing >1000 single nucleotide polymorphisms in a haploid genome

“…Several available techniques meet the second requirement (for review, see Brennan 2001;Kwok and Chen 2003), many of which are very efficient and cost-effective. The first requirement is usually met after DNA sequence amplification by the polymerase chain reaction (PCR) (Saiki et al 1985;Mullis and Faloona 1987).…”

Genomics and Pediatric Research

“…This was nicely demonstrated in the recent mapping of an asthma gene to chromosome 7 (52). Already there have been such significant advances in the development of genotyping (53) and microarray (54,55) technologies that within 5-10 y it might not be so unreasonable at birth or autopsy to resequence an individual's genome to extract medically relevant information (29,56,57). With all of the rapid progress in the field, any outright optimism is tempered by the fact that only a handful of multifactorial disease genes have been accurately mapped and, even less successfully, identified.…”

Identifying Biomarkers of Lung Cancer in the Post-Genomic Era

“…There are now a variety of ways to detect SNP in the genome (Brennan, 2001;Kwok, 2000;Kwok, 2001;Lindblad-Toh et al, 2000). Sequencing and single-stranded conformational polymorphism (SSCP) analysis has been widely used to detect SNPs.…”