Nonhuman primate models in the genomic era: a paradigm shift

Because of their strong similarities to humans across physiologic, developmental, behavioral, immunologic, and genetic levels, nonhuman primates are essential models for a wide spectrum of biomedical research. But unlike other animal models, nonhuman primates possess substantial outbred genetic variation, reducing statistical power and potentially confounding interpretation of results in research studies. Although unknown genetic variation is a hindrance in studies that allocate animals randomly, taking genetic variation into account in study design affords an opportunity to transform the way that nonhuman primates are used in biomedical research. New understandings of how the function of individual genes in rhesus macaques mimics that seen in humans are greatly advancing the rhesus macaques utility as research models, but epistatic interaction, epigenetic regulatory mechanisms, and the intricacies of gene networks limit model development. We are now entering a new era of nonhuman primate research, brought on by the proliferation and rapid expansion of genomic data. Already the cost of a rhesus macaque genome is dwarfed by its purchase and husbandry costs, and complete genomic datasets will inevitably encompass each rhesus macaque used in biomedical research. Advancing this outcome is paramount. It represents an opportunity to transform the way animals are assigned and used in biomedical research and to develop new models of human disease. The genetic and genomic revolution brings with it a paradigm shift for nonhuman primates and new mandates on how nonhuman primates are used in biomedical research.