Genetic characterization of specific pathogen-free rhesus macaque (Macaca mulatta) populations at the California National Primate Research Center (CNPRC)

Abstract

A study based on 14 STRs was conducted to understand intergenerational genetic changes that have occurred within the California National Primate Research Center's (CNPRC) regular specific pathogen-free (SPF) and super-SPF captive rhesus macaque populations relative to their conventional founders. Intergenerational genetic drift has caused age cohorts of each study population, especially within the conventional population, to become increasingly differentiated from each other and from their founders. Although there is still only minimal stratification between the conventional population and either of the two SPF populations, separate derivation of the regular and super-SPF animals from their conventional founders has caused the two SPF populations to remain marginally different from each other. The regular SPF and, especially, the super-SPF populations have been influenced by the effects of differential ancestry, sampling, and lost rare alleles, causing a substantial degree of genetic divergence between these subpopulations. The country of origin of founders is the principal determinant of the MHC haplotype composition of the SPF stocks at the CNPRC. Selection of SPF colony breeders bearing desired genotypes of Mamu-A*01 or -B*01 has not affected the overall genetic heterogeneity of the conventional and the SPF research stocks.Because misclassifying the ancestry of research stocks can undermine experimental outcomes by excluding animals with regional-specific genotypes or phenotypes of importance, understanding founder/descendent genetic relationships is crucial for investigating candidate genes with distinct geographic origins. Together with demographic management, population genetic assessments of SPF colonies can curtail excessive phenotypic variation among the study stocks and facilitate successful production goals.

Fig. 1

Proportions of Indian and Chinese ancestry assigned by STRUCTURE to rhesus macaques in each of the study populations (N = 737). Note the predominance of full blood Chinese, Chinese-Indian hybrid and full blood Indian animals in the conventional, regular SPF and Indian super-SPF populations, respectively. All Chinese super-SPF animals were assigned as full-blood Chinese rhesus macaques.

Fig. 2

Graph displays the frequency of Mamu-A*01 and –B*01 positive animals by birth cohort in the Indian and Chinese super-SPF subpopulations from 2003 to 2008.