Sequencing the CYP2D6 gene: from variant allele discovery to clinical pharmacogenetic testing
Yao Yang, Mariana R Botton, Erick R Scott, Stuart A Scott, Yao Yang, Mariana R Botton, Erick R Scott, Stuart A Scott
Abstract
CYP2D6 is one of the most studied enzymes in the field of pharmacogenetics. The CYP2D6 gene is highly polymorphic with over 100 catalogued star (*) alleles, and clinical CYP2D6 testing is increasingly accessible and supported by practice guidelines. However, the degree of variation at the CYP2D6 locus and homology with its pseudogenes make interrogating CYP2D6 by short-read sequencing challenging. Moreover, accurate prediction of CYP2D6 metabolizer status necessitates analysis of duplicated alleles when an increased copy number is detected. These challenges have recently been overcome by long-read CYP2D6 sequencing; however, such platforms are not widely available. This review highlights the genomic complexities of CYP2D6, current sequencing methods and the evolution of CYP2D6 from allele discovery to clinical pharmacogenetic testing.
Keywords: CYP2D6; CYP450-2D6; Sanger sequencing; genotyping; long-read sequencing; pharmacogenetics; pharmacogenomics; short-read sequencing.
Conflict of interest statement
Financial and competing interests disclosure
This work was supported in part by the National Institute of General Medical Sciences (NIGMS) of the NIH, through grant K23GM104401 (SA Scott). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
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Source: PubMed