Abstract
BackgroundMacaca fascicularis (cynomolgus or longtail macaques) is the most commonly used non-human primate in biomedical research. Little is known about the genomic variation in cynomolgus macaques or how the sequence variants compare to those of the well-studied related species, Macaca mulatta (rhesus macaque). Previously we identified single nucleotide polymorphisms (SNPs) in portions of 94 rhesus macaque genes and reported that Indian and Chinese rhesus had largely different SNPs. Here we identify SNPs from some of the same genomic regions of cynomolgus macaques (from Indochina, Indonesia, Mauritius and the Philippines) and compare them to the SNPs found in rhesus.ResultsWe sequenced a portion of 10 genes in 20 cynomolgus macaques. We identified 69 SNPs in these regions, compared with 71 SNPs found in the same genomic regions of 20 Indian and Chinese rhesus macaques. Thirty six (52%) of the M. fascicularis SNPs were overlapping in both species. The majority (70%) of the SNPs found in both Chinese and Indian rhesus macaque populations were also present in M. fascicularis. Of the SNPs previously found in a single rhesus population, 38% (Indian) and 44% (Chinese) were also identified in cynomolgus macaques. In an alternative approach, we genotyped 100 cynomolgus DNAs using a rhesus macaque SNP array representing 53 genes and found that 51% (29/57) of the rhesus SNPs were present in M. fascicularis. Comparisons of SNP profiles from cynomolgus macaques imported from breeding centers in China (where M. fascicularis are not native) showed they were similar to those from Indochina.ConclusionThis study demonstrates a surprisingly high conservation of SNPs between M. fascicularis and M. mulatta, suggesting that the relationship of these two species is closer than that suggested by morphological and mitochondrial DNA analysis alone. These findings indicate that SNP discovery efforts in either species will generate useful resources for both macaque species. Identification of SNPs that are unique to regional populations of cynomolgus macaques indicates that location-specific SNPs could be used to distinguish monkeys of uncertain origin. As an example, cynomolgus macaques obtained from 2 different breeding centers in China were shown to have Indochinese ancestry.
Highlights
Macaca fascicularis is the most commonly used nonhuman primate in biomedical research
There were a total of 69 single nucleotide polymorphisms (SNPs) in the cynomolgus macaque DNAs, with individual genes having between 2 and 13 polymorphisms (Figure 2a)
We found nearly the same number of SNPs associated with the Chinese rhesus macaques in both Indochinese and Indonesian populations, 19 and 20, respectively (Table 1)
Summary
Macaca fascicularis (cynomolgus or longtail macaques) is the most commonly used nonhuman primate in biomedical research. The M. fascicularis genome sequence, gene expression arrays and a SNP map are not yet available to advance complex trait analysis in cynomolgus macaques. An isolated population of cynomolgus macaques inhabits the island of Mauritius This population is widely considered to have descended from a small number of animals that arrived by trading ships 400–500 years ago [18,19]. This conclusion is supported by analysis of the major histocompatibility complex (MHC) allele distribution in the Mauritian animals, which carry a very limited number of alleles and haplotypes relative to other macaque populations [3,20,21]. Cynomolgus macaques are not native to China, and are descendants of animals imported from elsewhere
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