Genetic substructure in cynomolgus macaques (Macaca fascicularis) on the island of Mauritius

Abstract

BackgroundNonhuman primates are commonly used in biomedical research as animal models of human disease and behavior. Compared to common rodent models, nonhuman primates are genetically, physiologically, behaviorally and neurologically more similar to humans owing to more recent shared ancestry and therefore provide the advantage of greater translational validity in preclinical studies. The cynomolgus macaque (Macaca fascicularis) is one of the most commonly used nonhuman primates in academic and industry settings, yet population genetic research has revealed significant substructure throughout the species distribution that may confound studies. Cynomolgus monkeys introduced to Mauritius specifically have previously been thought to maintain the least genetic heterogeneity of all cynomolgus monkeys, although recent work, including work from our lab, suggests macaques from Mauritius too may harbor cryptic substructure.ResultsTo evaluate putative substructure in Mauritian cynomolgus macaques, we designed a panel of 96 single nucleotide polymorphisms based on preliminary findings from previous work to screen 246 of cynomolgus monkeys from two primary suppliers. Results from this study support substructure in Mauritian macaques and suggest a minimum of two populations and maybe three on Mauritius, with moderate admixture.ConclusionThese findings inform the natural history of these monkeys suggesting either a previously unrecognized physical or ecological barrier to gene flow on Mauritius and/or the breakdown of historic substructure resulting from the history of macaque introduction to the island. These findings are relevant to ongoing research using these models in part because of increased appreciation of segregating common variation with functional effects and may be used to better inform animal selection in preclinical research.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-748) contains supplementary material, which is available to authorized users.

Favipiravir Pharmacokinetics in Nonhuman Primates and Insights for Future Efficacy Studies of Hemorrhagic Fever Viruses

“…There are no data to our knowledge on the aldehyde oxidase phenotypes across macaque populations. However, it is known that Mauritian and Southeast Asian cynomolgus macaque populations have a genetic gap (28,29), and therefore, it is possible that this genetic difference explains the discrepancy in PK between the two species. Yet, and in spite of efforts to standardize the protocol studies and animal handling, the experiments were performed in two different laboratories, and thus, one cannot rule out that the differences found between the two species are due to confounding factors.…”

Genetic characterization of South American infectious bursal disease virus reveals the existence of a distinct worldwide-spread genetic lineage

“…We explore the independence of this distinct lineage using DAPC, a novel-specific multivariate method that identifies and describes clusters of genetically related entities maximizing the separation between groups and minimizing withingroup variation (Jombart et al, 2010). This method has been extensively applied in viruses, bacteria, eukaryotic unicellular parasites and metazoans to reveal population structuring using different genetic markers (Jombart et al, 2010;Ramírez et al, 2012;Ogawa & Vallender, 2014;Vernière et al, 2014). The analysis resolves five clusters corresponding to the four traditional IBDV strains plus the group of dIBDVs (Figure 3).…”

Biologic Data of Cynomolgus Monkeys Maintained under Laboratory Conditions

“…Non-human Primates (NHP) are the closest phylogenic relatives to man which makes them a suitable and sometimes indispensable model in many fields of biomedical research [ 1 – 4 ]. Macaca fascicularis (commonly called cynomolgus monkey) is a well-known NHP species widely used in various types of studies in pharmaceutical (toxicological, pharmacological, metabolic, physiological and psychological) research and development [ 5 – 9 ]. At present, the use of animals in biomedical research is limited to pre-screening tests, initial drug development phases, or when there is the supplementary aim of giving indications of the species to use in research projects on animals [ 10 – 12 ].…”

“…Evaluation of laboratory data should take into account possible differences in baseline values due to different animal sources and to the different analytical methods used in individual laboratories [ 6 – 9 , 19 ]. Physiological responses to stress conditions and induced reactions based on husbandry practice may also induce changes in clinical pathology parameters.…”