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• W2121253054 abstract "Cytochrome P450 2D6 (<i>CYP2D6</i>) is highly polymorphic. <i>CYP2D6-2D7</i> hybrid genes can be present in samples containing <i>CYP2D6</i>*<i>4</i> and <i>CYP2D6</i>*<i>10</i> alleles. <i>CYP2D7-2D6</i> hybrid genes can be present in samples with duplication signals and in samples with homozygous genotyping results. The frequency of hybrid genes in clinical samples is unknown. We evaluated 1390 samples for undetected hybrid genes by polymerase chain reaction (PCR) amplification, PCR fragment analysis, TaqMan copy number assays, DNA sequencing, and allele-specific primer extension assay. Of 508 <i>CYP2D6</i>*<i>4</i>-containing samples, 109 (21.5%) harbored <i>CYP2D6</i>*<i>68</i> + *<i>4</i>-like, whereas 9 (1.8%) harbored <i>CYP2D6</i>*<i>4N</i> + *<i>4</i>-like. Of 209 <i>CYP2D6</i>*<i>10</i>-containing samples, 44 (21.1%) were found to have <i>CYP2D6</i>*<i>36</i> + *<i>10</i>. Of 332 homozygous samples, 4 (1.2%) harbored a single <i>CYP2D7-2D6</i> hybrid, and of 341 samples with duplication signals, 25 (7.3%) harbored an undetected <i>CYP2D7-2D6</i> hybrid. Phenotype before and after accurate genotyping was predicted using a method in clinical use. The presence of hybrid genes had no effect on the phenotype prediction of <i>CYP2D6</i>*<i>4</i>- and <i>CYP2D6</i>*<i>10</i>-containing samples. Four of four (100%) homozygous samples containing a <i>CYP2D7-2D6</i> gene had a change in predicted phenotype, and 23 of 25 (92%) samples with a duplication signal and a <i>CYP2D7-2D6</i> gene had a change in predicted phenotype. Four novel genes were identified (<i>CYP2D6</i>*<i>13A1 variants 1</i> and <i>2</i>, <i>CYP2D6</i>*<i>13G1</i>, and <i>CYP2D6</i>*<i>13G2</i>), and two novel hybrid tandem structures consisting of <i>CYP2D6</i>*<i>13B</i> + *<i>68</i>×<i>2</i> + *<i>4</i>-like and <i>CYP2D6</i>*<i>13A1 variant 2</i> + *<i>1</i>×<i>N</i> were observed." @default.
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• W2121253054 date "2011-10-17" @default.
• W2121253054 modified "2023-10-06" @default.
• W2121253054 title "Frequency of Undetected <i>CYP2D6</i> Hybrid Genes in Clinical Samples: Impact on Phenotype Prediction" @default.
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• W2121253054 doi "https://doi.org/10.1124/dmd.111.040832" @default.
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