Open AccessResolving discordant CYP2D6 genotyping results in Thai subjects: platform limitations and novel haplotypes.
Author(s) -
Yaowaluck Hongkaew,
Wendy Y. Wang,
Roger Gaedigk,
Chonlaphat Sukasem,
Andrea Gaedigk
Publication year - 2021
Publication title -
pharmacogenomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.541
H-Index - 91
eISSN - 1744-8042
pISSN - 1462-2416
DOI - 10.2217/pgs-2021-0013
Subject(s) - genotyping , haplotype , sanger sequencing , biology , genotype , locus (genetics) , genetics , cyp2d6 , computational biology , dna sequencing , gene
Aim: Several CYP2D6 Luminex xTAG genotype calls were identified as inconsistent or suspicious among Thai subjects and further characterized to identify the root causes. Material & methods: Forty-eight subjects were followed-up with long-range-PCR, quantitative copy number assays and/or Sanger sequencing. Results: Most of the Luminex-duplication calls were either negative or had hybrid structures involving CYP2D6*36 in various configurations. Ten samples were inaccurately called as CYP2D6*2, *29 or *35 alleles. Sequencing revealed three novel haplotypes, CYP2D6*142, *143 and *144 of which two are nonfunctional. Conclusion: The Luminex platform produced a relatively high number of false genotype calls for Thai subjects. Our findings underscore the need for the systematic characterization of the CYP2D6 locus in diverse populations and rigorous platform validation.