SOUTHWEST FOUNDATION FOR BIOMEDICAL RESEARCH
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Genetics of Osteoporosis-related Phenotypes in Baboons

 Osteoporosis involves progressive structural deterioration of bone tissue, leading to bone fragility and increased risk of bone fracture. According to the National Osteoporosis Foundation, the well-being of 43.6 million people in the United States alone is currently endangered by low bone mass and skeletal fragility. The individual suffering and public health costs resulting from osteoporotic fractures are driving a great deal of research to identify the factors contributing to this painful and debilitating condition.

Our research uses pedigreed baboons to study the effects of genes and environment on bone maintenance and turnover. Nonhuman primate models are very important in bone studies. The baboon shares physiological and developmental characteristics with humans (including a relatively long lifespan, similar skeletal anatomy, bone loss with advancing age, and similar reproductive physiology and endocrinology) that make them particularly well-suited to studies of bone biology.

Osteoporosis is a complex disease resulting from a number of genetic and environmental factors affecting bone mass and architecture. Our research is concentrated on osteoporosis-related phenotypes that have been linked to osteoporosis risk in humans, including bone mineral density, serum measures of bone formation, and microscopic bone remodeling processes. After measuring these phenotypes, we use maximum-likelihood-based variance decomposition methods to assess heritability, to test for pleiotropic effects on two or more related phenotypes, and to test for genotype-by-“environment” interaction. In this case, “environment” may refer to the individual’s age, sex, or other covariate (e.g. reproductive history). We then conduct genome-wide linkage analyses to localize genetic effects to chromosomal regions. Once chromosomal regions have been located, we can identify positional candidate genes, or search for as yet unidentified genes, and test to see which are responsible for the observed effects.

The ultimate goal of this research is to improve our understanding of factors contributing to variation in the maintenance and repair of bone at the microstructural level and, by extension, susceptibility to osteoporosis and other age-related pathologies in bone.

Funded in part by:
The National Institute of Arthritis, Musculoskeletal, & Skin Diseases, National Institutes of Health
Department of Genetics, SFBR
A collaborative research contact with AxyS Pharmaceuticals, Inc. (formerly Sequana Therapeutics, Inc.), The San Antonio Area Foundation, The Southwest Foundation Forum, and the SFBR Founder's Council