International Journal of Legal Medicine

, Volume 132, Issue 4, pp 1007–1024 | Cite as

Full-gene haplotypes refine CYP2D6 metabolizer phenotype inferences

  • Frank R. Wendt
  • Antti Sajantila
  • Rodrigo S. Moura-Neto
  • August E. Woerner
  • Bruce Budowle
Original Article


CYP2D6 is a critical pharmacogenetic target, and polymorphisms in the gene region are commonly used to infer enzyme activity score and predict resulting metabolizer phenotype: poor, intermediate, extensive/normal, or ultrarapid which can be useful in determining cause and/or manner of death in some autopsies. Current genotyping approaches are incapable of identifying novel and/or rare variants, so CYP2D6 star allele definitions are limited to polymorphisms known a priori. While useful for most predictions, recent studies using massively parallel sequencing data have identified additional polymorphisms in CYP2D6 that are predicted to alter enzyme function but are not considered in current star allele nomenclature. The 1000 Genomes Project data were used to produce full-gene haplotypes, describe their distribution in super-populations, and predict enzyme activity scores. Full-gene haplotypes generated lower activity scores than current approaches due to inclusion of additional damaging polymorphisms in the star allele. These findings are critical for clinical implementation of metabolizer phenotype prediction because a fraction of the population may be incorrectly considered normal metabolizers but actually may be poor or intermediate metabolizers.


CYP2D6 Full-gene haplotypes Metabolizer phenotype Massively parallel sequencing 

Supplementary material

414_2017_1709_MOESM1_ESM.docx (225 kb)
ESM 1 (DOCX 225 kb)
414_2017_1709_MOESM2_ESM.xlsx (18.4 mb)
ESM 2 (XLSX 18845 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Frank R. Wendt
    • 1
    • 2
  • Antti Sajantila
    • 3
  • Rodrigo S. Moura-Neto
    • 4
  • August E. Woerner
    • 1
    • 2
  • Bruce Budowle
    • 1
    • 2
    • 5
  1. 1.Center for Human IdentificationUniversity of North Texas Health Science CenterFort WorthUSA
  2. 2.Graduate School of Biomedical SciencesUniversity of North Texas Health Science CenterFort WorthUSA
  3. 3.Laboratory of Forensic Biology, Department of Forensic MedicineUniversity of HelsinkiHelsinkiFinland
  4. 4.Instituto de BiologiaUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  5. 5.Center of Excellence in Genomic Medicine (CEGMR)King Abdulaziz UniversityJeddahSaudi Arabia

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