By Debbie Strickland

Sometimes the best place to begin looking for human genes is in baboons. At least that's true in the case of complex diseases like osteoporosis, in which both environmental and genetic factors are at play.

A research collaboration comprising a biotech firm, a big pharma company and a non-profit academic institute has mapped the baboon genome — including regions with genes linked to bone density — by studying an environmentally controlled colony of 700 baboons, whose multigenerational pedigrees stretch back to the early 1960s.

The collaborative partners are Sequana Therapeutics Inc., of La Jolla, Calif.; Boehringer Mannheim Group, of Amsterdam; and the Southwest Foundation for Biomedical Research (SFBR), the non-profit San Antonio institution that developed the colony.

With baboons, whose genome parallels closely that of humans, it's possible to breed and maintain four generations of test subjects who don't smoke, eat poorly or develop couch-potato habits — all non-genetic links to low bone density in humans that make the genetic component tough to isolate.

Now armed with a map of the Papio hamadryas (baboon) genome, including the bone-density determining segments, researchers at Sequana are attempting to identify rapidly the corresponding segments and genes in humans.

"If you find a region in the baboon genome that seems to contain a gene that controls bone density, it's very straightforward to go immediately to the corresponding region in the human genome and test to see if you get a signal for a bone density gene in that region of the human genome, and that's exactly what Sequana is doing," said Jeffrey Rogers, associate scientist in SFBR's department of genetics.

"The fact that they overlap, that some of the regions in the baboon overlap with the human regions is interesting," said Tim Harris, senior vice president of research and development and chief technical officer at Sequana. "It may be chance, but it's unlikely to be chance. It probably means there are real genes in these regions controlling bone density. That's what we're expecting and now we're chasing after them."

Sequana and SFBR's collaborative study of the baboon genome marks the first genetic use of baboons as a model organism for skeletal pathology, as well as the first comprehensive search in primates — human or non-human — for genes that contribute to osteoporosis.

Harris was "not at liberty" to discuss specific human gene candidates, but said, "It's all looking very interesting . . . We'll be mapping the regions, doing further studies to refine the regions, and finding the genes in the regions."

Over half the baboons in SFBR's colony live 20 years, roughly equivalent to age 60 in humans, and a few live as long as 25. Longer life spans lead to some of the same symptoms observed in elderly humans.

"They definitely get the same post-menopausal bone loss problems that humans do," said Harris. "They have the classical kyphosis, which is the curvature of the spine which you get in [elderly women]. It's exactly the same situation in baboons, they get bent like that."

The collaboration between Sequana and SFBR began in 1993, shortly after SFBR had independently launched an inquiry into the genetics of bone density.

Two years later, Sequana inked an osteoporosis gene-discovery deal with Boehringer Mannheim worth up to $50 million, plus royalties, on the sale of therapeutic and diagnostic products. Boehringer Mannheim has exclusive rights to develop and commercialize therapeutic and diagnostic products based on genes discovered as a result of the collaboration. *