Development and validation of a SNP-based assay for inferring the genetic ancestry of rhesus macaques (Macaca mulatta)

Abstract

Rhesus macaques (Macaca mulatta) are an important primate model species in several areas of biomedical research. The wide geographic distribution of this species has led to significant genetic differentiation among local and regional populations. These regional differences can be important factors in the selection of the most appropriate subjects for particular research studies, as animals from different populations can respond differently to the same experimental treatment. Consequently, it is valuable to confirm the ancestry of individual rhesus monkeys from geographically distinct populations. Using DNA samples obtained from rhesus macaques from six National Primate Research Centers, we tested a set of 384 potential ancestry informative single nucleotide polymorphisms (SNPs) and identified a final panel of 91 SNPs that can reliably distinguish Indian-origin from Chinese-origin rhesus monkeys. This genetic test can be used to determine the ancestral origin of animals and to detect individuals that are hybrids between these two regional populations. To demonstrate use of the SNP panel, we investigated the ancestry of 480 animals from the Yerkes NPRC (YNPRC) for which the colony records were insufficient to clearly establish ancestry. Three of the YNPRC animals tested were determined to be hybrids. This SNP ancestry tool will be useful to researchers, colony managers, and others who wish to evaluate the ancestral origin of individual rhesus macaques, and therefore will facilitate more effective and efficient use of these animals in biomedical research.

Keywords: ancestry; genetic management; rhesus.

Fig. 1

The fractional genetic ancestry (Q) of each individual rhesus macaque (represented by a vertical bar) derived from the calculated Chinese (light grey) and Indian (dark grey) clusters, as estimated by STRUCTURE. Thirteen individuals predicted to have greater than 15% hybrid ancestry are indicated with an ‘h’. An additional three offspring/parent pairs (‘1/2’, ‘3/4’, ‘5/6’) with predicted hybrid ancestry are shown. A Chinese rhesus that was misclassified as an Indian rhesus and a 75% Indian animal that was misclassified as a 25% Indian rhesus are indicated with an ‘m’.

Fig. 2

The first two PCA axes differentiating pure Chinese, Indian and hybrid rhesus macaques explain approximately 75% and 15% of the variation respectively.

Fig. 3

The probability of assignment or fractional ancestry (Q) of each individual rhesus macaque in the retest panel (represented by a vertical bar) derived from the putative Chinese (dark grey) and putative Indian (light grey) samples, as estimated by STRUCTURE. Eight individuals are labeled with ‘h’ to indicate that they have greater than 15% hybrid ancestry. A 75% Indian animal that was misclassified as a 25% Indian rhesus in Figure 1 is indicated with an ‘m’ in this figure.

Fig. 4

With the exception of three individuals, all animals among the YNPRC sample were assigned to 85% or greater Indian ancestry and were considered pure Indian ancestry.