omation mbers - Society for Laboratory Automation and Screening
omation mbers - Society for Laboratory Automation and Screening
omation mbers - Society for Laboratory Automation and Screening
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
2:00 pm Thursday, February 5 Clinical – Pharmacogenomics Room C1<br />
Carl Yamashiro<br />
Amersham Biosciences<br />
3200 W. Germann Road<br />
Ch<strong>and</strong>ler, Arizona 85248<br />
carl.yamashiro@amersham.com<br />
120<br />
Co-Author(s)<br />
Buena Chui, M. Roxane Bonner, Michael Gaskin,<br />
Penny Gwynne, Jeffrey Winick, Arkadiy Silbergleit<br />
Amersham Biosciences<br />
Annalee Ledesma<br />
University of Cali<strong>for</strong>nia, San Diego<br />
Population Studies Using Enhanced Version of the CodeLink P450 SNP Bioarrays Yield<br />
New <strong>and</strong> Novel Genotype <strong>and</strong> Haplotype Frequency Data<br />
A significant part of variation in drug efficacy <strong>and</strong> safety is of a hereditary nature, <strong>and</strong> <strong>for</strong> many instances can<br />
be traced down to polymorphisms in genes involved in drug metabolism. Establishing correlations between<br />
drug metabolizing phenotypes <strong>and</strong> P450 genotypes <strong>and</strong> haplotypes will facilitate the drug discovery process,<br />
make clinical trials safer, <strong>and</strong> provide the next step to personalized medicine. CodeLink SNP bioarrays from<br />
Amersham Biosciences are robust tools <strong>for</strong> broad-based single nucleotide polymorphism (SNP) genotyping, which<br />
can be used in linkage mapping or c<strong>and</strong>idate gene profiling. The assay is simple, straight<strong>for</strong>ward, <strong>and</strong> highly<br />
efficient assay with high throughput capabilities. For SNP detection, CodeLink plat<strong>for</strong>m uses enzymatic allele<br />
specific extension (ASE) of oligonucleotide probes. Templates <strong>for</strong> ASE are generated by highly specific long-range<br />
multiplex PCR, despite high DNA homology within the P450 gene subfamilies, followed by amplicon purification<br />
<strong>and</strong> fragmentation. The genotyping assay has been streamlined <strong>and</strong> simplified <strong>for</strong> facile h<strong>and</strong>ling <strong>and</strong> more rapid<br />
time to results. CodeLink SNP P450 bioarrays allow <strong>for</strong> genotyping of 110 SNPs in nine genes: CYP1A1, CYP1A2,<br />
CYP1B1, CYP2C19, CYP2C9, CYP2D6, CYP2E, CYP3A4, <strong>and</strong> CYP3A5. We sequenced 46 samples from three<br />
major populations at all of these loci to calculate assay accuracy. From Coriell Human Diversity panels, 230<br />
samples were genotyped <strong>and</strong> population-specific allele <strong>and</strong> inferred haplotype frequencies have been determined.<br />
There are several interesting haplotypes within a few of the P450 genes <strong>for</strong> certain populations that have potential<br />
clinical ramifications with respect to pharmacogenetic outcomes.
Change language