The comparative expression analysis of liver samples from 36 animals of different geographic origin resulted in the identification of over 700 genes with highly variable expression while the majority of the transcriptome showed relatively stable expression with low inter-animal variation. Interestingly enough, considerable inter-individual as well as inter-species variability was found in gene expression levels of a number of drug safety and response related genes. Variation in gene expression among individuals can be critical for the interpretation of drug safety data and genome-wide gene expression profiling can now be used to improve drug safety studies and discover the mode of action of novel drugs in a relevant animal model.
"The flexibility and accuracy of the NimbleGen expression microarray platform allowed us to develop a novel microarray based on our genome sequencing effort. For the first time, gene expression can be monitored with high-specificity in this animal model to answer mechanistic or safety related questions based on transcriptional responses. Furthermore, we plan to design additional arrays for copy-number-variation and SNP analysis on the NimbleGen array platform. These combined efforts will hopefully improve the translational value of non-human primate experiments for humans. As in humans, it might become possible in the future to discover polymorphisms in drug-response genes that differentiate poor and good metabolizers for instance" explained Prof. Ulrich Certa, principle lead of the project.
"The knowledge we obtained from the cynomolgus genome and gene expression profiling using NimbleGen microarrays is an important contribution towards the better use of this species as a drug safety model for the assessment of novel human drugs. In particular, the publishe
|SOURCE Roche Diagnostics GmbH|
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