Genome-based analysis of the nonhuman primate Macaca fascicularis as a model for drug safety assessment
- Martin Ebeling1,
- Erich Küng2,
- Angela See3,
- Clemens Broger4,
- Guido Steiner1,
- Marco Berrera1,
- Tobias Heckel2,
- Leonardo Iniguez3,
- Thomas Albert3,
- Roland Schmucki1,
- Hermann Biller4,
- Thomas Singer2 and
- Ulrich Certa2,5
- 1Translational Research Sciences, F. Hoffmann-La Roche AG, Pharmaceutical Research and Early Development (pRED), 4070 Basel, Switzerland;
- 2Global Non-clinical Safety, F. Hoffmann-La Roche AG, Pharmaceutical Research and Early Development (pRED), 4070 Basel, Switzerland;
- 3Roche NimbleGen, Inc., Madison, Wisconsin 53719, USA;
- 4Research Informatics, F. Hoffmann-La Roche AG, Pharmaceutical Research and Early Development (pRED), 4070 Basel, Switzerland
Abstract
The long-tailed macaque, also referred to as cynomolgus monkey (Macaca fascicularis), is one of the most important nonhuman primate animal models in basic and applied biomedical research. To improve the predictive power of primate experiments for humans, we determined the genome sequence of a Macaca fascicularis female of Mauritian origin using a whole-genome shotgun sequencing approach. We applied a template switch strategy that uses either the rhesus or the human genome to assemble sequence reads. The sixfold sequence coverage of the draft genome sequence enabled discovery of about 2.1 million potential single-nucleotide polymorphisms based on occurrence of a dimorphic nucleotide at a given position in the genome sequence. Homology-based annotation allowed us to identify 17,387 orthologs of human protein-coding genes in the M. fascicularis draft genome, and the predicted transcripts enabled the design of a M. fascicularis–specific gene expression microarray. Using liver samples from 36 individuals of different geographic origin we identified 718 genes with highly variable expression in liver, whereas the majority of the transcriptome shows relatively stable and comparable expression. Knowledge of the M. fascicularis draft genome is an important contribution to both the use of this animal in disease models and the safety assessment of drugs and their metabolites. In particular, this information allows high-resolution genotyping and microarray-based gene-expression profiling for animal stratification, thereby allowing the use of well-characterized animals for safety testing. Finally, the genome sequence presented here is a significant contribution to the global “3R” animal welfare initiative, which has the goal to reduce, refine, and replace animal experiments.
Footnotes
-
↵5 Corresponding author.
E-mail ulrich.certa{at}roche.com.
-
[Supplemental material is available for this article.]
-
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.123117.111
- Received March 9, 2011.
- Accepted July 11, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
Freely available online through the Genome Research Open Access option.
