CYP2D6基因测序：从变异等位基因发现到临床药物遗传学检测
Sequencing the CYP2D6 gene: from variant allele discovery to clinical pharmacogenetic testing.
作者信息
Yang Yao, Botton Mariana R, Scott Erick R, Scott Stuart A
机构信息
Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Icahn Institute for Genomics & Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
出版信息
Pharmacogenomics. 2017 May;18(7):673-685. doi: 10.2217/pgs-2017-0033. Epub 2017 May 4.
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.
细胞色素P450 2D6（CYP2D6）是药物遗传学领域中研究最多的酶之一。CYP2D6基因具有高度多态性，有超过100个已编目的星号（*）等位基因，并且临床CYP2D6检测越来越容易获得，并有实践指南的支持。然而，CYP2D6基因座的变异程度及其与假基因的同源性使得通过短读长测序来分析CYP2D6具有挑战性。此外，当检测到拷贝数增加时，准确预测CYP2D6代谢酶状态需要分析重复的等位基因。这些挑战最近已通过长读长CYP2D6测序得以克服；然而，此类平台尚未广泛应用。本综述重点介绍了CYP2D6的基因组复杂性、当前的测序方法以及CYP2D6从等位基因发现到临床药物遗传学检测的发展历程。
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