title: Characterization of 137 Genomic DNA Reference Materials for 28 Pharmacogenetic Genes: A GeT-RM Collaborative Project.
abstract: Pharmacogenetic testing is increasingly available from clinical laboratories. However, only a limited number of quality control and other reference materials are currently available to support clinical testing. To address this need, the Centers for Disease Control and Prevention-based Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing community and the Coriell Cell Repositories, has characterized 137 genomic DNA samples for 28 genes commonly genotyped by pharmacogenetic testing assays (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP4F2, DPYD, GSTM1, GSTP1, GSTT1, NAT1, NAT2, SLC15A2, SLC22A2, SLCO1B1, SLCO2B1, TPMT, UGT1A1, UGT2B7, UGT2B15, UGT2B17, and VKORC1). One hundred thirty-seven Coriell cell lines were selected based on ethnic diversity and partial genotype characterization from earlier testing. DNA samples were coded and distributed to volunteer testing laboratories for targeted genotyping using a number of commercially available and laboratory developed tests. Through consensus verification, we confirmed the presence of at least 108 variant pharmacogenetic alleles. These samples are also being characterized by other pharmacogenetic assays, including next-generation sequencing, which will be reported separately. Genotyping results were consistent among laboratories, with most differences in allele assignments attributed to assay design and variability in reported allele nomenclature, particularly for CYP2D6, UGT1A1, and VKORC1. These publicly available samples will help ensure the accuracy of pharmacogenetic testing.
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Pratt
authors.affiliation: Agena Bioscience, San Diego, California.
authors.forename: Robin E
authors.initials: RE
authors.lastname: Everts
authors.affiliation: Section of Genomic Pediatrics, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Praful
authors.initials: P
authors.lastname: Aggarwal
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Beyer
authors.affiliation: Section of Genomic Pediatrics, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Broeckel
authors.affiliation: Department of TechSupport, Autogenomics Inc., Vista, California.
authors.forename: Ruth
authors.initials: R
authors.lastname: Epstein-Baak
authors.affiliation: Department of Research & Development, Autogenomics Inc., Vista, California.
authors.forename: Paul
authors.initials: P
authors.lastname: Hujsak
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Ruth
authors.initials: R
authors.lastname: Kornreich
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jun
authors.initials: J
authors.lastname: Liao
authors.affiliation: Section of Genomic Pediatrics, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Rachel
authors.initials: R
authors.lastname: Lorier
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Scott
authors.affiliation: Department of Research & Development, Autogenomics Inc., Vista, California.
authors.forename: Chingying Huang
authors.initials: CH
authors.lastname: Smith
authors.affiliation: Coriell Cell Repositories, Coriell Institute for Medical Research, Camden, New Jersey.
authors.forename: Lorraine H
authors.initials: LH
authors.lastname: Toji
authors.affiliation: Section of Genomic Pediatrics, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Amy
authors.initials: A
authors.lastname: Turner
authors.affiliation: Division of Laboratory Systems, Centers for Disease Control and Prevention, Atlanta, Georgia. Electronic address: lkalman@cdc.gov.
authors.forename: Lisa V
authors.initials: LV
authors.lastname: Kalman
mesh_terms: D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D060005:Genotyping Techniques; D014453:Glucuronosyltransferase / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D014481:United States
chemical_list: D002352:Carrier Proteins; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase