The Olive Branch: Researchers Harness Expertise To Study Granddaughter’s Rare Bone Condition

Story by Jennifer Gauntt, VMBS Marketing & Communications

October 7, 2025

A pair of VMBS scientists have been working to bring hope to families everywhere by dedicating their efforts to understanding a rare genetic disorder.

As a toddler, Olive walked in a way that her grandmother, Dr. Dana Gaddy, described as an exaggerated “waddle.” 

But this wasn’t the “waddle” of an infant learning to walk — Olive’s “waddle” was the result of a bowing in her legs caused by a flare at the end of her bones, which “made her joints work a little bit differently,” said Gaddy, a professor in the Texas A&M College of Veterinary Medicine & Biomedical Sciences (VMBS).

When Olive’s parents realized something was wrong, they took her to specialists to determine the cause, to no avail. In the meantime, Olive’s issues persisted. One day, she was sitting at her grandparents’ house eating a grape when her tooth fell out, root and all.

“By the time she started having her secondary teeth come in, she was 8 years old, and she’d already lost all of her incisors, all of her canines, and two molars,” Gaddy said. “She was pretty snaggle-toothed for a long time.” 

One day, Gaddy and husband Dr. Larry Suva — both musculoskeletal researchers who were working at the University of Arkansas for Medical Sciences at the time — attended a conference session on hypophosphatasia (HPP), a rare genetic disorder in which the enzyme alkaline phosphatase is mutated. HPP is characterized by the abnormal development of bones and teeth caused by defective mineralization in the body. 

“A really good friend of ours, who is one of the world’s clinician experts in the disease, showed a picture of a tooth from a child with hypophosphatasia; the tooth had come out, root and all,” Suva said. “It was only a month after our granddaughter lost her tooth while eating a grape at our house. We both thought, ‘That looks just like Olive’s tooth! Olive has that disease!’”

The couple called a clinical geneticist colleague, who sequenced Olive’s alkaline phosphatase gene; the results revealed that not only were her levels extremely low, but she also had two mutations in the same gene.

With a name to a problem, Gaddy and Suva began to investigate. They learned that HPP can be quite debilitating in humans, and it is also extremely rare, with severe forms affecting approximately 1 in 100,000 to 300,000 people and milder forms affecting as many as 1 in 6,300 adults, according to the Cleveland Clinic.

The pair decided to harness their knowledge and take matters into their own hands, starting a project that not only brought them to the VMBS but also held transformative potential for a disease about which very little is known.

Taking Research Personally

To better understand HPP, Suva and Gaddy turned to the VMBS’ Dr. Charles Long and the late Dr. Mark Westhusin, genetic engineering experts, for a possible collaboration in developing a large animal model that would allow them to better understand HPP’s progression — a crucial step in developing treatments for any disease. 

After visiting Texas A&M, the two, instead, decided to join the VMBS faculty — Suva in the Department of Veterinary Physiology & Pharmacology and Gaddy in the Department of Veterinary Integrative Biosciences.

At Texas A&M, the pair used CRISPR-Cas9 technology to replicate the genetic mutations that cause HPP and create the exact same phenotype that affects their granddaughter in what they now call “The Olive Sheep.” These sheep, which exhibit identical HPP symptoms as their granddaughter, have allowed the duo to make tremendous progress in developing a more complete understanding of HPP in patients as they age. 

“We’ve been able to see what happens when they’re 2 or 3 years old and how that is impacting them when they’re 6 or 7,” Suva said.

Starting the project in late 2016, they quickly saw signs of success, publishing papers and even receiving federal funding from agencies like the National Institutes of Health’s (NIH) National Institute of Dental and Craniofacial Research and the Soft Bones Foundation to support their endeavors. 

More recently, Gaddy also received funding from the NIH’s National Heart, Lung, and Blood Institute to study the connections between HPP, lung function, and respiratory distress. 

This, too, has come from watching their granddaughter, now 15, as she grows and then comparing her experience against the experience of sheep born with HPP. 

“We noticed that the animals seemed to get tired quickly. So does Olive,” Suva said. “If there’s a cold going around school, Olive’s going to get it, and while everyone else feels better in three days, Olive’s going to take a week — or longer. It’s a fact now; that anecdotal thing Dana had noted in the sheep, we noted it in Olive.”

‘Community’ Science

Ever the true scientists, Gaddy and Suva recognize that as anecdotal evidence, Olive is a single example. But as the couple began comparing notes with their clinical counterparts and other researchers, that one has become many, many more.  

“We began asking our clinician colleagues; they’ve got 30 patients and 20 of them have the same problem. Suddenly, our sheep have become a predictor of what will happen to Olive — because she is still our primary interest; our Olive is the reason we do this,” Suva said. “We’ve learned that it’s not just Olive’s HPP; it’s everybody’s HPP — our Olive sheep have been way more constructive and predictive than I had imagined.” 

More recently, Gaddy and Suva have become active with the non-profit patient advocacy group Soft Bones, Inc., and regularly invite families affected by HPP to Texas A&M both to meet other HPP families in the region and to learn more about the work they’re doing — and the disease itself. 

At one meeting for HPP families from the south central region, the pair shared the effects of what’s become known as “the lazy phenotype” — a milder form of HPP that appears in early adolescents and is sometimes seen in individuals who carry a single variant (an allele) of the HPP gene; this can lead to a severe lack of endurance in affected individuals.  

“We shared that in families with more than one child, their other children may also have an HPP mutation, but perhaps only one allele is affected,” Gaddy said. “So that child may appear to not be affected by HPP, but they may carry ‘the lazy phenotype.’ This has helped those parents understand why that child won’t go for a walk or may start something but can’t finish it; it’s not because they don’t want to but because they physically don’t have the stamina to last through the whole event.”

Suva and Gaddy originally noticed the phenomenon in their sheep and then contacted their clinical colleagues to verify that this observation was also being observed in human patients. 

This kind of “symbiotic” relationship — between the researcher, the medical community, and the families affected by HPP — has led to increased interest in HPP, which, in turn, has led to a deeper understanding of the disease and the recognition that HPP is “way more” prevalent than people realize, according to Gaddy. 

“We’ve learned that women who carry only one allele will start losing their teeth at menopause,” she said. “These are women who have had great dental hygiene, no cavities. They’ve taken care of their teeth, and then, suddenly, their teeth loosen and these post-menopausal women start having periodontal disease.” 

In fact, today, more than 400 HPP mutations are recognized. These kinds of findings — along with their own — are part of what drive Gaddy and Suva in their mission to learn as much as possible about HPP and, hopefully, be a part of new treatment solutions.  

“All of this has come from the last 10 years of researching this disorder, and we’re going to fix it; we’re going to find a way,” Suva said. “Even if we don’t fix it for Olive, we’re going to fix it, because if she ever has children, HPP could be a problem for them, too.

“As researchers, we have always done things to try to improve people’s lives. This project got a bit closer to the bone.”

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on Facebook, Instagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of VMBS Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences, jgauntt@cvm.tamu.edu, 979-862-4216

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