Typing Human Cytochrome P450 Genes Using DNA Chips

We will develop DNA chips capable of detecting and characterizing mutations in the human CYP2D6 (cyP450 2D6) gene. These chips will be used to correlate drug metabolism phenotype with specific mutatinaturally in the human population. CYP2D6 mutations result in dramatic differences in drug efficacyof the Caucasian population and 2% of Asian populations. In Phase I will (1) design and synthesize Dcomplementary to exons 1-9 and intron/exon splice sites of the CYP2D6 gene (1567 coding bp and 180 idevelop a PCR amplification strategy using multiplex PCR for the genomic form of the gene, and (3) dhybridization protocol that will test the sequence calling performance of the DNA chips. During Phasknown CYP2D6 mutations will be used as model targets to test heterozygous and homozygous mutant detethey will test the DNA chips for their mutation detection performance in characterized and uncharactsamples obtained from phenotyped patients.