Haplotype phasing ofCYP2D6: an allelic ratio method using Agena MassARRAY data

Abstract

Pharmacogenomics aims to use the genetic information of an individual to personalize drug prescribing. There is evidence that pharmacogenomic testing before prescription may prevent adverse drug reactions, increase efficacy, and reduce cost of treatment.CYP2D6is a key pharmacogene of relevance to multiple therapeutic areas. Indeed, there are prescribing guidelines available for medications based on CYP2D6 enzyme activity as deduced fromCYP2D6genetic data. The Agena MassARRAY system is a cost-effective method of detecting genetic variation that has been clinically applied to other genes. However, its clinical application toCYP2D6has to date been limited by weaknesses such as the inability to determine which haplotype was present in more than one copy for individuals with more than two copies of theCYP2D6gene. We report application of a new protocol forCYP2D6haplotype phasing of data generated from the Agena MassARRAY system. For samples with more than two copies of theCYP2D6gene for which the prior consensus data specified which one was present in more than one copy, our protocol was able to conductCYP2D6haplotype phasing resulting in 100% concordance with the prior data. In addition, for three reference samples known to have more than two copies ofCYP2D6but for which the exact number ofCYP2D6genes was unknown, our protocol was able to resolve the number for two out of the three of these, and estimate the likely number for the third.

Haplotype phasing of CYP2D6: an allelic ratio method using Agena MassARRAY data

“…For CNV calls, the automated reports provide a functional CNV call (denoting the total number of functional CYP2D6 haplotypes), as well as an overall CNV call (denoting the total number of CYP2D6 copies). Using a method we developed [47], we conducted haplotype phasing by calculating the ratios of the peak heights of variant to reference alleles per SNP.…”