| Publication Abstract Display | | Type: Published Manuscript | | Title: SNP genotyping using TaqManH
technology: the CYP2D6*17 assay
conundrum. | | Authors: Gaedigk A, Freeman N, Hartshorne T, Riffel AK, Irwin D,
Bishop JR, Stein MA, Newcorn JH, LKM Jaime, Cherner M, Leeder JS | | Year: 2015 | | Publication: Scientific Reports | | Volume: March Issue: Pages: | | Abstract:CYP2D6 contributes to the metabolism of many clinically used drugs and is increasingly tested to
individualize drug therapy. The CYP2D6 gene is challenging to genotype due to the highly complex nature
of its gene locus. TaqManH technology is widely used in the clinical and research settings for genotype
analysis due to assay reliability, low cost, and the availability of commercially available assays. The assay
identifying 1023C.T (rs28371706) defining a reduced function (CYP2D6*17) and several nonfunctional
alleles, produced a small number of unexpected diplotype calls in three independent sets of samples, i.e. calls
suggested the presence of a CYP2D6*4 subvariant containing 1023C.T. Gene resequencing did not reveal
any unknown SNPs in the primer or probe binding sites in any of the samples, but all affected samples
featured a trio of SNPs on their CYP2D6*4 allele between one of the PCR primer and probe binding sites.
While the phenomenon was ultimately overcome by an alternate assay utilizing a PCR primer excluding the
SNP trio, the mechanism causing this phenomenon remains elusive. This rare and unexpected event
underscores the importance of assay validation in samples representing a variety of genotypes, but also
vigilance of assay performance in highly polymorphic genes such as CYP2D6. |
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