Andersson, T

Aspegren, A

Bjorquist, P

Hilgendorf, C

Mills, T

Nicholls, G

P, [Unknown]

Pilling, M.

Sartiby, [Unknown]

We have conducted a pilot study to assess the robustness of SNP genotyping by the Affymetrix DMET™plus platform in the hands of Beckman Coulter Genomics , to develop data handling, statistical analysis and modelling methods and to characterise six pre-clinical cell lines &amp; tissues and 72 samples from a healthy volunteer study. The Affymetrix DMET™ Plus Panel represents 1936 genetic variants (1931 SNPs or In-Dels and five copy number region markers) in 225 genes of importance to ADME. These include the 32 core genes of importance to the PharmADME consortium of academic &amp; pharmaceutical researchers. One hundred and sixty-nine of these variants are located in genes that are currently classified as known valid biomarkers according to the FDA (http://www.fda.gov). The six human pre-clinical samples consisted of HepaRG, Caco2, two cryopreserved hepatocytes and two embryonic stem cell lines. A further six control samples representing blinded triplicates were included for QC purposes. Thorough QC has shown that the quality of the data generated was very high; successful genotype data (for over 98% of the SNPs on the panel) in 82 of the 84 samples tested was generated. Two samples (both cell-lines) fell below this threshold even after repeat analysis. In addition, 98% of SNPs analysed produced genotype calls for &gt;95% of the 84 samples. Genotype concordance &gt;99.9% was observed from two control samples triplicated and 100% genotype concordance was observed in 20 SNPs genotyped by Taqman. Hardy-Weinberg Equilibrium testing of the 72 healthy volunteer samples further suggested that there were no gross genotyping errors. Approximately 65% of the variants of the DMET™ Plus Panel are reported to have a minor allele frequency of less than 5% and this was reflected in our observation that 41.2% of the SNPs were polymorphic in the 72 Caucasian volunteer samples. Data will be presented describing the information obtained for these cell lines

The University of Manchester - Institutional Repository

Affymetrix DMET™Plus Genotyping Technology: Evaluation of Cell Lines and Healthy Volunteer Samples

Affymetrix DMET™Plus Genotyping Technology: Evaluation of Cell Lines and Healthy Volunteer Samples

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The University of Manchester - Institutional Repository