Pharmacogenomics, Identity Testing, and Related Molecular Applications
Pharmacogenomics
Know the core genes and their clinical implications: CYP2D6, CYP2C19, CYP2C9, TPMT/NUDT15, DPYD, HLA-B57:01, HLA-B15:02, and VKORC1. Understand star allele nomenclature, phenotype categories (poor, intermediate, normal, rapid/ultrarapid metabolizer), and how copy number and structural variation affect CYP2D6. Be able to translate genotype to phenotype to drug recommendation using CPIC/DPWG guidance.
Identity testing
Understand STR profiling (loci, allele calling, kinship vs forensic), the difference between a match probability and a random match probability, and the role of chimerism testing after transplant. Know the concepts of sample identity, contamination, and the need for a reference sample.
Traps
Items conflate genotype with phenotype (a genotype does not always equal a metabolizer status because of unknown alleles or drug interactions), ignore phenoconversion (inhibitors converting a normal metabolizer to poor), or misinterpret HLA allele screening (low-resolution vs high-resolution typing). For identity testing, watch for questions about the number of loci required and about maternal cell contamination.
Rule of thumb
Report pharmacogenomic results as genotype plus predicted phenotype plus therapeutic implication, and flag when phenoconversion or an untested allele could alter the prediction. For identity, require a reference and document the loci and match criteria.
Worked example
A patient is CYP2D6 *1/*4 (one no-function allele): predicted intermediate metabolizer. If the patient is also on a strong CYP2D6 inhibitor, phenoconversion to poor metabolizer status should be considered when interpreting drug response.