Progress in Genetics and Genomics of Nonhuman Primates

The papers in this issue of the ILAR Journal discuss the current understanding of the genetics and genomics of apes (particularly the chimpanzee), and old world monkeys, such as macaques, baboons, and vervets. These species provide highly relevant models for many aspects of human physiology, behavior, and disease. They also enhance the understanding of evolutionary biology. These animals have been used widely for many aspects of discovery science. As directly related to translational research, monkeys, in particular, are used extensively to test the efficacy of vaccines, therapies for human disease, and for examining the toxicity of drug candidates. Classic examples of the importance of nonhuman primates (NHPs) used for translational research are the development of vaccines for polio (Sabin 1985; Salk and Salk 1984), hepatitis A (Purcell and Emerson 2001), and hepatitis B (Chisari 2000). Nonhuman primates' (NHPs) utility for both discovery and translational science stems primarily from three factors. First, NHPs are closely related to humans in terms of evolutionary history. Therefore, humans and NHPs share many common features of physiology, behavior, and genetics. Rodents are the mammals most commonly used for basic, testable discoveries that can potentially correlate with human physiology. For many types of studies, use of NHPs, rodents, and other model organisms are synergistic. There is often no single animal that models a human condition perfectly. However, there are many instances in which rodents are simply too different from humans to answer certain questions. For example, rodents have only limited utility for studies in the field of neurobiology because they do not have the requisite complexity of brain structures, social organization, or cognitive abilities to adequately model certain human conditions (Bauman et al. 2013; Capitanio and Emborg 2008; Vallender and Miller 2013). A second reason to use NHPs in research is the ability to control environment and diet. For example, this feature has facilitated studies of caloric restriction(definition) on aging (Colman et al. 2009; Mattison et al. 2012) and the effects of maternal diet on fetal development (Antonow-Schlorke et al. 2011; Sullivan and Grove 2010). Finally, for more than 50 years, the US National Institutes of Health (NIH) and other agencies have funded centralized primate research centers, which house well characterized, disease-free colonies of NHPs for research. They also provide resources and intellectual know-how for investigators performing research on NHPs. In addition to the United States, countries in Africa, Asia, and Europe have developed primate centers that fulfill these functions. Centralized facilities have reduced the cost of performing experiments using NHPs, and have substantially increased the quality of animals, including monkeys free of specific pathogens and genetically characterized animals. As an example, the eight United States National Primate Research Centers house approximately 26,000 NHPs and support at least 1000 different investigations per year. The funding for these efforts comes from the NIH, other United States governmental agencies, foundations, and commercial entities. These investigations cover research into a wide range of organ systems and diseases. Detailed knowledge of an experimental organism's genome, particularly its sequence, greatly enhances the utility of that animal model for both discovery and translational research. Sequencing of the human genome (Gonzaga-Jauregui 2012) is correctly viewed as a fundamental achievement of modern biological investigation. The availability of a human genome sequence has facilitated many additional studies that have provided information about human genomic diversity, including genetic loci involved in control of gene expression. It has catalyzed the development of new technologies, including genetic mapping, using single nucleotide polymorphisms and rapid sequencing of exomes to elucidate the genetic basis of both complex and single-gene disorders. Sequencing the mouse genome (Mouse Genome Sequencing Consortium 2002), combined with developments in recombinant DNA technology and reproductive biology, has made it possible to create genetically modified animals that can be used to show the function of specific genes. As for humans and rodents, detailed genomic and genetic knowledge of NHPs is required for optimal use when explaining the causes of disease and for pre-clinical testing of therapies. An additional, unique use of genetic analysis in NHPs is the role it plays in colony management and in the selection of animals for specific experiments. Regarding colony management, it is important to maintain genetic diversity, since the size of breeding colonies is limited. This is particularly true for Indian origin rhesus macaques, which are a major type of NHP used for studies of HIV/AIDs, and cannot be imported from India. Therefore, it is difficult to add new genetic variants to the Indian rhesus colonies and correspondingly important not to lose diversity. Genetic testing is essential for the management of Indian rhesus colonies. Regarding experimental design, NHPs are expensive relative to rodents and should be used in relatively small numbers for any given investigation. It can be important to account for specific types of genetic variation when using NHPs in experiments. For example, specific alleles of the rhesus major histocompatibility complex (MHC) have variable effects on immune responses, which can influence the results of vaccine challenges or transplantation experiments (Shen et al. 2013; Wiseman et al. 2013). Significant progress has been made in NHP genomics and genetics in the past several years. A partial list is presented here to provide a sense of the diversity of information available. This topic is amplified in the various articles in this issue of the ILAR Journal. Some key advances are: derivation of the draft genome sequences of the