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Mol Diagn. 1999 Dec;4(4):343-51.

Technologies for detecting genetic polymorphisms in pharmacogenomics.

Author information

1
Genomic Pathology Laboratory, Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research, Warner-Lambert Company, Ann Arbor, Michigan 48105, USA. michael.shi@wl.com

Abstract

BACKGROUND:

Pharmacogenomics is an emerging scientific discipline examining the genetic basis for individual variations in response to therapeutics.

METHODS AND RESULTS:

Genetic polymorphisms are a major cause of individual differences in drug response. Metabolic phenotyping can be accomplished by administering a probe drug or substrate and measuring the metabolites and clinical outcomes. However, this approach tends to be labor intensive and requires repeated sample collection from the individual being tested. Alternatively, genotyping allows determination of individual DNA sequence differences for a particular trait. Commonly used genotyping methods include gel electrophoresis-based techniques, such as polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism analysis, multiplex PCR, and allele-specific amplification. Fluorescent dye-based high-throughput genotyping procedures are increasing in popularity, including oligonucleotide ligation assay, direct heterozygote sequencing, and TaqMan (Perkin Elmer, Foster City, CA) allelic discrimination. High-density chip array and mass spectrometry technologies are the newest advances in the genotyping field, but their wide application is yet to be developed. Novel mutations/polymorphisms also can be identified by conformation-based mutation screening and direct high-throughput heterozygote sequencing.

CONCLUSIONS:

Rapid and accurate detection of genetic polymorphisms has great potential for application to drug development, animal toxicity studies, improvement of human clinical trials, and postmarket monitoring surveillance for drug efficacy and toxicity.

PMID:
10671645
DOI:
10.154/MODI00400343
[Indexed for MEDLINE]
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