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The CYP2D6 VCF Translator

The Pharmacogenomics Journal volume 17, pages 301–303 (2017)Cite this article

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The cytochrome P450-2D6 (CYP2D6) hepatic oxidase is directly involved in the metabolism of ~25% of all commonly used drugs,1, 2, 3 making it one of the most well-studied genes in the field of pharmacogenetics. As is likely well known by the readership of The Pharmacogenomics Journal, the CYP2D6 gene is highly polymorphic, with over 100 variant star (*) alleles currently cataloged by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee.4 This committee was formed in 1999 to manage CYP450 allele nomenclature using established sequence variation guidelines and to provide a summary of curated star (*) alleles and their effects when known;5 however, the field of pharmacogenetics has been transformed by the recent advances in high-throughput sequencing technologies. Although next-generation sequencing has greatly facilitated pharmacogenomic discovery,6, 7, 8 one of the resultant challenges is now reconciling the historical star (*) allele nomenclature with current genome reference assemblies and a more informed understanding of the extent of variation in the human genome.9

Interrogating CYP2D6 by short-read sequencing technologies is challenging due to pseudogene sequence homology and the existence of copy number variant CYP2D6 alleles.10 In addition, one of the most cumbersome informatics issues is converting identified CYP2D6 sequence variants from the genome assembly used for sequence analysis (for example, GRCh37/hg19) to the M33388.1 or AY545216.1 GenBank reference sequences used to define CYP2D6 star (*) alleles (http://www.cypalleles.ki.se/cyp2d6.htm). This tedious but necessary process typically is accomplished by manual curation, but recently assisted by the CYP2D6 haplotype tables available at PharmGKB (https://www.pharmgkb.org).

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Acknowledgements

This research was supported in part by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) through grant K23 GM104401 (SAS), and the computational resources and staff expertise provided by the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai.

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Authors and Affiliations

  1. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    W Qiao, J Wang, R Chen, Y Yang & S A Scott

  2. Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA,

    J Wang & R Chen

  3. Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA

    B S Pullman

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  1. W Qiao
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Correspondence to S A Scott.

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Qiao, W., Wang, J., Pullman, B. et al. The CYP2D6 VCF Translator. Pharmacogenomics J 17, 301–303 (2017). https://doi.org/10.1038/tpj.2016.14

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