SNP genotyping using TaqMan technology: the CYP2D6*17 assay conundrum

Scientific Reports
Andrea GaedigkJ S Leeder

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. TaqMan 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 o...Continue Reading

References

Jun 26, 2003·Nucleic Acids Research·Michael Zuker
Nov 18, 2003·Naunyn-Schmiedeberg's Archives of Pharmacology·Ulrich M ZangerMichel Eichelbaum
Jan 22, 2004·The Pharmacogenomics Journal·T E Klein, R B Altman
Jan 30, 2007·Clinical Pharmacology and Therapeutics·A GaedigkJ Steven Leeder
Aug 13, 2008·Analytical and Bioanalytical Chemistry·Ulrich M ZangerMatthias Schwab
Oct 13, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Nov 12, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Dec 22, 2009·Biosensors & Bioelectronics·Dasheng LeeGwo-Bin Lee
Apr 16, 2011·Pharmacology·Wojciech Leppert
Dec 22, 2011·Drug Metabolism and Pharmacokinetics·Lay Kek Teh, Leif Bertilsson
Mar 15, 2013·Clinical Pharmacology and Therapeutics·J K HicksUNKNOWN Clinical Pharmacogenetics Implementation Consortium
Oct 25, 2013·International Review of Psychiatry·Andrea Gaedigk
Jan 25, 2014·Clinical Pharmacology and Therapeutics·K R CrewsUNKNOWN Clinical Pharmacogenetics Implementation Consortium
Jul 6, 2014·Best Practice & Research. Clinical Anaesthesiology·Andrea M Trescot
Oct 21, 2014·PloS One·Deise C FriedrichMara H Hutz

❮ Previous
Next ❯

Citations

Jan 23, 2016·Frontiers in Pharmacology·Amanda K RiffelAndrea Gaedigk
Apr 5, 2013·PloS One·Anastasia FedickNathan R Treff
Jun 2, 2015·PloS One·Ricardo Usategui-MartínRogelio González Sarmiento
Jul 12, 2018·Pharmacogenomics·Monpat ChamnanphonChonlaphat Sukasem
Jul 19, 2018·Pharmacogenomics·Charity Nofziger, Markus Paulmichl
Sep 6, 2017·Omics : a Journal of Integrative Biology·Fernando de AndrésAdrián LLerena
Sep 24, 2019·Clinical Pharmacology and Therapeutics·Charity NofzigerAndrea Gaedigk
Sep 19, 2018·Analytical Chemistry·Kenny Malpartida-CardenasPantelis Georgiou

❮ Previous
Next ❯

Datasets Mentioned

BETA
AY545216
M33388

Methods Mentioned

BETA
genotyping
PCR
electrophoresis

Software Mentioned

Mfold
TaqMan®
SDS2
SeqScape

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.