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.

Keywords: cardiovascular disease; diabetes; genomics resources; hypertension; intrauterine growth restriction; metabolic syndrome; obesity; osteoporosis.

Figure 1

An example of the structure of one of the sub-pedigrees (a sire family) within the seven-generation pedigree that has been used extensively in complex disease genetics research at the Southwest National Primate Research Center to date. The sire (identified by the arrow) is located near the middle of generation 3 of this pedigree. Square symbols represent males; circles represent females; symbols bisected by diagonal lines indicate a dead animal. Lines drawn upward from solid dots (nodes) identify mated pairs. Lines descending from nodes identify offspring of mated pairs. The sub-pedigree displayed in this figure has been cropped for display purposes; it is considerably larger and more complex than shown. Within each of the major sub-pedigrees in the seven-generation, single-pedigree configuration, there are many moderately sized large full sibships (5–7 members) nested within large half sibships (up to 100 members).

Figure 2

Papio hamadryas anubis (Olive baboon)

Figure 3

Comparison of human and baboon chromosomes. (A) Conservation of microsatellite marker order for orthologs human 12 and baboon 11. (B) Chromosome inversion between orthologs human 4 and baboon 5. The y-axis indicates chromosome length in centimorgans. Microsatellite markers identified in human have identification numbers that begin with “D,” and microsatellite markers identified in baboon have identification numbers that begin swith “Pha”.