Comprehensive assessment of metabolic enzyme and transporter genes using the Affymetrix Targeted Genotyping System.
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.
Dumaual
Carmen
C
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Miao
Xin
X
Daly
Thomas M
TM
Bruckner
Carsten
C
Njau
Reuben
R
Fu
Dong-Jing
DJ
Close-Kirkwood
Sandra
S
Bauer
Nancy
N
Watanabe
Nancy
N
Hardenbol
Paul
P
Hockett
Richard D
RD
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
D026901:Membrane Transport Proteins