Correction: Methodology for clinical genotyping of CYP2D6 and CYP2C19

Henriques, Beatriz Carvalho; Buchner, Amanda; Hu, Xiuying; Wang, Yabing; Yavorskyy, Vasyl; Wallace, Keanna; Dong, Rachael; Martens, Kristina; Carr, Michael S.; Asl, Bahareh Behroozi; Hague, Joshua; Sivapalan, Sudhakar; Maier, Wolfgang; Dernovšek, Mojca Zvezdana; Henigsberg, Neven; Twarowska-Hauser, Joanna; Souery, Daniel; Cattaneo, Annamaria; Mors, Ole; Rietschel, Marcella; Pfeffer, Gerald; Hume, Stacey; Aitchison, Katherine J.

doi:10.1038/s41398-022-01845-w

Cited by 2 publications

(11 citation statements)

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“…DNA samples used were from the Genome-based therapeutic drugs for depression (GENDEP) study, comprising patients of European ancestry. 24 The majority of these had prior data using the AmpliChip CYP450 Test (Roche Molecular Systems, Pleasanton, USA), as mentioned, a previously available assay for CYP2D6 and CYP2C19 variants. 24 In addition, positive controls from the Genetic Testing Reference Material Program (GeT-RM) 31 were used: NA02016 (previously genotyped using the AmpliChip CYP450 Test as CYP2D6*17/*2XN), NA17221 (consensus CYP2D6*1XN/*2), and NA17439 (previously genotyped using the AmpliChip CYP450 Test as CYP2D6*4XN/*41).…”

Section: Samplesmentioning

confidence: 99%

“…There is one assay that was previously available and able to conduct haplotype phasing for a number of CYP2D6XNs (duplications/multiplications, specifically *1, *2, *4, *10, *17, *35, and *41), the AmpliChip CYP450 Test. 24 Although this assay had this capability, it had weaknesses (as we and others have shown 24 ), and was therefore withdrawn.…”

Section: Pharmacogenomics Aims To Use the Genetic Information Of An I...mentioning

confidence: 99%

“…24 The majority of these had prior data using the AmpliChip CYP450 Test (Roche Molecular Systems, Pleasanton, USA). 24 In addition, positive controls from the Genetic Testing Reference Material Program (GeT-RM) 31 were used: NA02016 (previously genotyped using the AmpliChip CYP450 Test as CYP2D6*17/*2XN), NA17221 (consensus CYP2D6*1XN/*2), and NA17439 (previously genotyped using the AmpliChip CYP450 Test as CYP2D6*4XN/*41).…”

Section: Samplesmentioning

confidence: 99%

“…These include TaqMan Single Nucleotide Polymorphism (SNP) and Copy Number Variant (CNV) assays for CYP2D6, the Luminex xTAG CYP2D6 v3 kit, the Ion Ampliseq Pharmacogenomics Panel, PharmacoScan Solution, Agena Bioscience assays such as the Veridose Core Panel, and digital PCR. [24][25][26][27][28][29][30] However, none of these at present claims to be able to conduct haplotype phasing for CYP2D6. There is one assay that was previously available and able to conduct haplotype phasing for a number of CYP2D6XNs (duplications/multiplications, specifically *1, *2, *4, *10, *17, *35, and *41), the AmpliChip CYP450 Test.…”

Section: Pharmacogenomics Aims To Use the Genetic Information Of An I...mentioning

confidence: 99%

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

Thamilselvan

Mather

Wang

et al. 2023

Preprint

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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.

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Section: Samplesmentioning

confidence: 99%

Section: Pharmacogenomics Aims To Use the Genetic Information Of An I...mentioning

confidence: 99%

Section: Samplesmentioning

confidence: 99%

Section: Pharmacogenomics Aims To Use the Genetic Information Of An I...mentioning

confidence: 99%

See 2 more Smart Citations

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

Thamilselvan

Mather

Wang

et al. 2023

Preprint

Self Cite

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show abstract

“…For example, the AmpliChip CYP450 Test did not cover hybrid haplotypes, and hence none of the 19 patients subsequently identified as having hybrid haplotypes had previously had these found, with 2 having been genotyped as CYP2D6*1/*1 (wild-type) and 4 as 'no call' 43 . We have previously reported the use of methods including Sanger sequencing to characterize hybrid haplotypes [43][44][45] . However, Sanger sequencing poses limitations for haplotype phasing (determining which combination of variants lies on which allele) and discriminating whether sequence is derived from CYP2D6 or CYP2D7 46 .…”

Section: Introductionmentioning

confidence: 99%

Single molecule long-read real-time amplicon-based sequencing ofCYP2D6: a proof-of-concept with hybrid haplotypes

Dong

Thamilselvan

et al. 2022

Preprint

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CYP2D6 is a widely expressed human xenobiotic metabolizing enzyme, best known for its role in the hepatic phase I metabolism of up to 25% of prescribed medications, which is also expressed in other organs including the brain, where its potential role in physiology and mental health traits and disorders is under further investigation. Owing to the presence of homologous pseudogenes in the CYP2D locus and transposable repeat elements in the intergenic regions, the gene encoding the CYP2D6 enzyme, CYP2D6, is one of the most hypervariable known human genes - with more than 140 core haplotypes. Haplotypes include structural variants, with a subtype of these known as fusion genes comprising part of CYP2D6 and part of its adjacent pseudogene, CYP2D7. The fusion genes are particularly challenging to identify. The CYP2D6 enzyme activity corresponding to some of these fusion genes is known, while for others it is unknown. The most recent (high fidelity, or HiFi) version of single molecule real-time (SMRT) long-read sequencing can cover whole CYP2D6 haplotypes in a single continuous sequence read, ideal for structural variant detection. In addition, the accuracy of base calling has increased to a level sufficient for accurate characterization of single nucleotide variants. As new CYP2D6 haplotypes are continuously being discovered, and likely many more remain to be identified in populations that are relatively understudied to date, a method of characterization that employs sequencing with at least this degree of accuracy is required. The aim of the work reported herein was to develop an efficient and accurate HiFi SMRT amplicon-based method capable of detecting the full range of CYP2D6 haplotypes including fusion genes. We report proof-of-concept for 20 amplicons, aligned to fusion gene haplotypes, with prior cross-validation data. Amplicons with CYP2D6-D7 fusion genes aligned to *36, *63, *68, and *4 (*4-like; *4N, or *4.013) hybrid haplotypes. Amplicons with CYP2D7-D6 fusion genes aligned to the *13 subhaplotypes predicted (e.g., *13F, *13A2). Data analysis was efficient, and further method development indicates that this technique could suffice for the characterization of the full range of CYP2D6 haplotypes. Although included in drug labelling by regulatory bodies (the U.S. Food and Drug Administration, the European Medicines Agency, the Pharmaceuticals and Medical Devices Agency) and prescribing recommendations by consortia (Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group), the identification of CYP2D6 variants is not yet routine in clinical practice. The HiFi sequencing method reported herein is suitable for high throughput, efficient, identification of the full range of known CYP2D6 haplotypes and novel haplotypes, and can be completed in a week or less. Moreover, the method that we have developed could be extended to other complex loci and to other species in a multiplexed high throughput assay.

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Correction: Methodology for clinical genotyping of CYP2D6 and CYP2C19

Cited by 2 publications

References 0 publications

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

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

Single molecule long-read real-time amplicon-based sequencing ofCYP2D6: a proof-of-concept with hybrid haplotypes

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