title: Enabling large-scale pharmacogenetic studies by high-throughput mutation detection and genotyping technologies.
abstract: BACKGROUND
  Pharmacogenetics is a scientific discipline that examines the genetic basis for individual variations in response to therapeutics. Pharmacogenetics promises to develop individualized medicines tailored to patients' genotypes. However, identifying and genotyping a vast number of genetic polymorphisms in large populations also pose a great challenge.
  
  
  METHODS
  This article reviews the recent technology development in mutation detection and genotyping with a focus on genotyping of single nucleotide polymorphisms (SNPs).
  
  
  BACKGROUND
  Novel mutations/polymorphisms are commonly identified by conformation-based mutation screening and direct high-throughput heterozygote sequencing. With a large amount of public sequence information available, in silico SNP mapping has also emerged as a cost-efficient way for new polymorphism identification. Gel electrophoresis-based genotyping methods for known polymorphisms include PCR coupled with restriction fragment length polymorphism analysis, multiplex PCR, oligonucleotide ligation assay, and minisequencing. Fluorescent dye-based genotyping technologies are emerging as high-throughput genotyping platforms, including oligonucleotide ligation assay, pyrosequencing, single-base extension with fluorescence detection, homogeneous solution hybridization such as TaqMan, and molecular beacon genotyping. Rolling circle amplification and Invader assays are able to genotype directly from genomic DNA without PCR amplification. DNA chip-based microarray and mass spectrometry genotyping technologies are the latest development in the genotyping arena.
  
  
  CONCLUSIONS
  Large-scale genotyping is crucial to the identification of the genetic make-ups that underlie the onset of diseases and individual variations in drug responses. Enabling technologies to identify genetic polymorphisms rapidly, accurately, and cost effectively will dramatically impact future drug and development processes.
authors.affiliation: Department of Applied Genomics, Genometrix Inc., The Woodlands, TX 77381, USA. mshi@genometrix.com
authors.forename: M M
authors.initials: MM
authors.lastname: Shi
mesh_terms: D005838:Genotype; D006801:Humans; D013058:Mass Spectrometry; D009154:Mutation; D009690:Nucleic Acid Conformation; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics / Q000379:methods*; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods