Pharmacogenetics: technologies to detect copy number variations.

Abstract

The human genome is characterized by structural variations, in addition to having expansive areas of tandem repeat sequences and SNPs. Copy number variations (CNVs) in the human genome are the result of insertions, deletions, duplications and complex multisite variants, affecting approximately 10 to 12% of the genome and covering a higher number of nucleotides than SNPs. Several methods are used for the detection of CNVs, including approaches based on hybridization, such as arrays, PCR amplification, FRET and sequencing. These methods can identify microscopic structural variations (> or = 3 Mb in size), as well as submicroscopic structural variations (approximately 1 kb to 3 Mb in size). CNVs can affect drug metabolism and disease susceptibility. Therefore, the effect of variations in the copies of genes on the efficacy and toxicity of therapeutic agents needs to be well established at both pharmacokinetic and pharmacodynamic levels prior to the use of these agents clinically. This review evaluates the techniques for detecting the CNVs available at the time of publication, citing examples from the application of CNVs in clinical pharmacogenetics.