Undergraduate Summer Student Job Details
Elucidation of complex drug metabolizing enzyme genetic variants
Dr Katherine J Aitchison
Katz 5-020, Katz Group Center for Pharmacy and Health Research
Pharmacogenomics is a type of personalized medicine in which genomic factors predicting treatment efficacy and adverse effects are identified. Such genetic factors include variants in drug metabolizing enzymes, such as CYP2D6. This enzyme has four levels of activity, corresponding to poor metabolizers (no active enzyme), normal metabolizers (normal enzyme activity), intermediate metabolizers (reduced enzyme activity), or ultrarapid metabolizers (increased enzyme activity). Ultrarapid metabolizers usually have more than one active copy of CYP2D6 (e.g., CYP2D6*1XN) in tandem on the chromosome. Other individuals have variants comprising part of the CYP2D6 gene and part of its adjacent pseudogene. Historically it has been challenging to detect these complex types of variants efficiently. The lab is currently piloting novel methodology for this, including long-range PCR with various platforms for subsequent identification of specific variants in the amplicons thereby generated. Such characterization will facilitate more in-depth association analysis with clinical variables.