MU College of Veterinary Medicine research determines genetic mutations cause rare genetic disorder

MU College of Veterinary Medicine finds a gene mutation responsible for causing Chédiak-Higashi syndrome.

A recent discovery by Leslie Lyons and Reuben Buckley of the College of Veterinary Medicine determined a specific mutation. It started with a collaboration with the Cincinnati Zoo, in which Lyons worked with a 16-year-old male cat named Smokey.

Smokey was the last biomedical cat model for the Chédiak-Higashi syndrome before passing away. Lyons and Buckley created a DNA map of Smokey with the syndrome. Through in vitro fertilization, a formerly extinct feline disease model was excavated.

According to the MU News Bureau website, Chédiak-Higashi syndrome is a rare condition in which the immune system is weakened and leaves the body more vulnerable to infections. It is a section of the genetic code that has been copied and pasted right next to it, which causes the frames to shift so the proteins do not work normally.

“I thought along the way ‘we should try to find the DNA mutation because that’s one of the reasons why other researchers didn’t pick up the project because you need to know what the DNA mutation is,’” Lyons said.

According to the MU News Bureau website, identifying genetic diseases caused by DNA gives researchers and clinicians ideas on how to treat diseases.

While reproduction specialists at the Cincinnati Zoo were resurrecting Smokey by assisted reproduction, Lyons and Buckley were searching for the gene. They both did genome sequencing, and Buckley knew what specific gene to look for and how to bind the mutation using a computer.

“We were able to genotype the cats and prove they were carriers of the mutation, which is what we would expect from Smokey,” Lyons said.

Smokey was a carrier of the disease, and all of his offspring was expected to also be a carrier of the mutation. They were still able to resurrect new cats that had mutation and have stored their embryos.

The team realized this experiment would be a perfect story to show how cryopreservation is important for animal models in that one doesn’t necessarily have to keep all of the cats in a cat colony. Cryopreservation is process of preserving organelles, tissues and cells by cooling them to extreme temperatures. They are able to bring back the colonies when they want or can expand and diversify them when needed also.

The goal of a researcher is the three R’s: refine, reduce, replace. If the team is able to preserve the cats with the mutation, they do not have to have the cat colonies sitting around in cages and are able to be more efficient.

Lyons said the most interesting aspect of the research was the complexity of the DNA variant the team found. They were able to get 11 offspring from Smokey and found three of which carried the mutation.

When Buckley stitched together the mutation, the team knew where to look because of years of prior experiments. Buckley said it was quite easy to notice a large section of the DNA had been manipulated.

“The fact that [it was] a successful experiment and how the team knew it was successful because we were first able to identify the mutation once we knew what we were looking at was the most rewarding thing out of this,” Buckley said.

Edited by Alex Fulton |

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