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Transcriptome profiling in five vitally important tissues of Cynomolgus monkeys using customized NimbleGen microarrays

ABSTRACT: Cynomolgus monkeys are well-established translational models for biomedical research and drug testing. To evaluate organ transcriptomes and gene expression variability in Cynomolgus monkeys, we used Customized NimbleGen Microarrays (Design ID: 120419_Cynomolgus_v5_TH_exp_HX12) for genome-wide gene expression profiling on 5 different tissues (heart, kidney, liver, lung, spleen) from 21 Cynomolgus monkeys. Cynomolgus monkey samples were derived from breeding centers located in the Philippines (3 females and 3 males), in Vietnam (2 females and 2 males), in China for animals from Mainland Southeast Asia (3 females), or in Mauritius (4 females and 4 males). Furthermore, genome-wide copy number variation was analyzed in tissue samples from the same animals using a custom NimbleGen 4.2 million probes comparative genomic hybridization (CGH) array to associate CNV genotypes with expression changes of proximal genes.

ORGANISM(S): Macaca fascicularis

PROVIDER: GSE76560 | GEO | 2016/02/24

SECONDARY ACCESSION(S): PRJNA307978

REPOSITORIES: GEO

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Project description:The long-tailed macaque, also referred to as cynomolgus monkey (Macaca fascicularis), is one of the most important non-human 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 which employs either the rhesus or the human genome to assemble sequence reads. The 6-fold 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. A 36-microarray study using total RNA recovered from liver samples of untreated Cynomolgus monkeys of good laboratory practice (GLP) drug safety studies. The monkeys were from the Philippines, a Chinese colony, and Mauritius. Each microarray measures the expression level of 16,896 genes using 20,047 probe sets with six 60-mer probes (PM) per probe set. Each probe set is represented once on the array. The Cynomolgus monkey gene expression results analyzed in this study are further described in Ebeling et al. (2011) (PMID 21862625).

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Transcriptome profiling in five vitally important tissues of Cynomolgus monkeys using customized NimbleGen microarrays

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