Genome-wide copy number variation profiling in Cynomolgus monkeys using customized NimbleGen CGH microarrays

Cynomolgus monkeys are well-established translational models for biomedical research and drug testing. Cynomolgus monkeys are outbred species and exhibit substantial levels of genetic variation which can affect the outcome and interpretation of biomedical studies. Copy number variations (CNVs) are a significant source of genetic diversity and a comprehensive understanding of the genomic impact of CNVs on phenotypic traits is limited. A custom 4.2 million probes comparative genomic hybridization (CGH) array (Design-ID: 120405_Cynomolgus5_CGH_UX1) has been designed on the basis of the Cynomolgus monkey genome (Ebeling et al. (2011) Genome Research; PMID: 21862625) to assess genome-wide copy number variation among Cynomolgus monkeys. Using Cynomolgus monkey specific NimbleGen CGH Microarrays we profiled the genomes of 21 Cynomolgus monkeys. Germline DNA from 21 Cynomolgus monkeys with different origin was tested against a Cynomolgus monkey reference. Cynomolus monkey samples were derived from breeding centers located in the Philippines (3 females and 3 males), in Vietnam (2 males and 2 females), in China for animals from Mainland Southeast Asia (3 females), or in Mauritius (4 females and 4 males). Furthermore genome-wide expression profiles were analyzed in 5 vitally important tissue samples (heart, kidney, liver, lung, spleen) from the same animals using a custom Cynomolgus monkey specific NimbleGen gene expression microarray (design ID: 120419_Cynomolgus_v5_TH_exp_HX12) to associate CNV genotypes with expression changes of proximal genes using a cis expression quantitative trait loci (cis-eQTL) mapping approach. Expression data have been deposited at the NCBI Gene Expression Omnibus (GEO) under accession numbers GSE76560. The array CGH results analyzed in this study are further described in Gschwind A.R. et al. (2016) "Diversity and regulatory impact of copy number variation in the primate Macaca fascicularis". under submission A NimbleGen customized 4.2M Whole-Genome Tiling CGH Array [design ID: 120405_Cynomolgus5_CGH_UX1] study using genomic DNA recovered from tissues of drug-naive Cynomolgus monkeys. The CGH microarray measures the fluorescence intensity ratio of dye-labeled DNA fragments from test samples relative to a reference across 4.2 million 50-75mer probes spanning the Cynomolgus monkey genome with a median spacing of 598 bp. Germline DNA from 21 Cynomolgus monkeys with different origin was tested against a Cynomolgus monkey reference. The reference was made of DNA from blood samples taken from Cynomolgus monkeys from centers located in Mauritius (25 males). The design includes Labeling Hybridization Control (LHC) probes for the estimation of copy number amplifications and deletions of spike-in 7 kb plasmid DNAs.