Baboons as a Model to Study Genetics and Epigenetics of Human Disease

Abstract

A major challenge for understanding susceptibility to common human diseases is determining genetic and environmental factors that influence mechanisms underlying variation in disease-related traits. The most common diseases afflicting the US population are complex diseases that develop as a result of defects in multiple genetically controlled systems in response to environmental challenges. Unraveling the etiology of these diseases is exceedingly difficult because of the many genetic and environmental factors involved. Studies of complex disease genetics in humans are challenging because it is not possible to control pedigree structure and often not practical to control environmental conditions over an extended period of time. Furthermore, access to tissues relevant to many diseases from healthy individuals is quite limited. The baboon is a well-established research model for the study of a wide array of common complex diseases, including dyslipidemia, hypertension, obesity, and osteoporosis. It is possible to acquire tissues from healthy, genetically characterized baboons that have been exposed to defined environmental stimuli. In this review, we describe the genetic and physiologic similarity of baboons with humans, the ability and usefulness of controlling environment and breeding, and current genetic and genomic resources. We discuss studies on genetics of heart disease, obesity, diabetes, metabolic syndrome, hypertension, osteoporosis, osteoarthritis, and intrauterine growth restriction using the baboon as a model for human disease. We also summarize new studies and resources under development, providing examples of potential translational studies for targeted interventions and therapies for human disease.

The baboon (Papio sp.) as a model for female reproduction studies

“…Baboons have already been used on a wide variety of reproductive studies, including pregnancy [40, 41, 42, 43,] fetal development [44, 45,] pharmacokinetics of compounds in pregnancy [46, 47,] abortifactant drugs [48,]nutrient restriction and the maternal/fetal relationship [49,] genetics [50,] endometriosis [51, 52,] hormonal [14, 16, 21, 53, 54, 55, 56,] temporary contraception [57, 58,] embryonic stem cells and ART [13,] pathology [59, 60,] and permanent contraception [18.] Their temperament and similarities to human anatomy warrant their continued use for reproductive studies.…”

Cross-species analyses unravel the complexity of H3K27me3 and H4K20me3 in the context of neural stem progenitor cells

“…As epigenetic landscapes are vulnerable to culture artifact and obtaining endogenous cells freshly from healthy human brain is ethically unacceptable, we purified in vivo NSPCs from baboon brain for genome-wide approach to identify putative targets of H3K27me3 and H4K20me3. Given the extensive correlation of brain structure (Rogers et al, 2010; Kochunov et al, 2010) and genomic similarity between baboon and human (Cox et al, 2013), findings regarding epigenetic regulation in baboon models may hold significant relevance to healthy and neuropathological conditions in human. Therefore, we utilized a previously described technique to purify subpopulations of in vivo SVZ cells from baboon brain (Sandstrom et al, 2014) for genome-wide analyses including chromatin immunoprecipitation followed by sequencing (ChIP-Seq) and RNA-Seq.…”

Advantages of nonhuman primates as preclinical models for evaluating stem cell-based therapies for Parkinson's disease

“…The baboon was the first NHP for which a detailed genetic linkage map was generated (Cox et al, 2013), and the baboon genome is now largely complete and available (https://www.hgsc.bcm.edu/baboongenome-project-0). The Southwest National Primate Research Center currently houses baboons with well documented pedigrees spanning eight or more generations, with genotyping data and banked biomaterials that represent a unique resource for tracing heritable contributions to disease progression.…”