title: Comprehensive assessment of metabolic enzyme and transporter genes using the Affymetrix Targeted Genotyping System.
abstract: The combined effects of multiple polymorphisms in several drug-metabolizing enzyme and transporter genes can contribute to considerable interindividual variation in drug disposition and response. Therefore, it has been of increasing interest to generate scalable, flexible and cost-effective technologies for large-scale genotyping of the drug-metabolizing enzyme and transporter genes. However, the number of drug-metabolizing enzyme and transporter gene variants exceeds the capacity of current technologies to comprehensively assess multiple polymorphisms in a single, multiplexed assay. The Targeted Genotyping System (Affymetrix, CA, USA) provides a solution to this challenge, by combining molecular inversion probe technology with universal microarrays to provide a method that is capable of analyzing thousands of variants in a single reaction, while remaining relatively insensitive to cross-reactivity between reaction components. This review will focus on the Targeted Genotyping System and how this technology was adapted to enable comprehensive analysis of drug-metabolizing enzyme and transporter gene polymorphisms.
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Dumaual
authors.forename: Xin
authors.initials: X
authors.lastname: Miao
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Daly
authors.forename: Carsten
authors.initials: C
authors.lastname: Bruckner
authors.forename: Reuben
authors.initials: R
authors.lastname: Njau
authors.forename: Dong-Jing
authors.initials: DJ
authors.lastname: Fu
authors.forename: Sandra
authors.initials: S
authors.lastname: Close-Kirkwood
authors.forename: Nancy
authors.initials: N
authors.lastname: Bauer
authors.forename: Nancy
authors.initials: N
authors.lastname: Watanabe
authors.forename: Paul
authors.initials: P
authors.lastname: Hardenbol
authors.forename: Richard D
authors.initials: RD
authors.lastname: Hockett
mesh_terms: D018390:Gene Targeting / Q000379:methods* / Q000639:trends; D005821:Genetic Techniques / Q000639:trends; D005838:Genotype; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D010597:Pharmacogenetics / Q000379:methods / Q000639:trends; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins