Faculty Collaboration Database

Characterization of 137 Genomic DNA Reference Materials for 28 Pharmacogenetic Genes: A GeT-RM Collaborative Project. J Mol Diagn 2016 Jan;18(1):109-23

Date

12/02/2015

Pubmed ID

26621101

Pubmed Central ID

PMC4695224

DOI

10.1016/j.jmoldx.2015.08.005

Scopus ID

2-s2.0-84954064957 (requires institutional sign-in at Scopus site)   132 Citations

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.

Author List

Pratt VM, Everts RE, Aggarwal P, Beyer BN, Broeckel U, Epstein-Baak R, Hujsak P, Kornreich R, Liao J, Lorier R, Scott SA, Smith CH, Toji LH, Turner A, Kalman LV

Authors

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin
Amy Turner Research Scientist I in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Base Sequence
Carrier Proteins
Cell Line
Cytochrome P-450 Enzyme System
Drug-Related Side Effects and Adverse Reactions
Genetic Testing
Genotype
Genotyping Techniques
Glucuronosyltransferase
Glutathione Transferase
High-Throughput Nucleotide Sequencing
Humans
Pharmacogenetics
Polymorphism, Single Nucleotide
Sequence Analysis, DNA
United States