Cat Genomics Littered with Disease Identification Opportunities

Findings from a new study could help feline preservationists implement breeding strategies in captivity for rare and endangered species such as the African black-footed cat (pictured above). [WikiCommons]

Cats and the internet go together like PB&J, so when researchers at the University of Missouri decided to use some of the latest cutting-edge genomic methods to study feline genetic variation and improve health among the animals, the decision seemed like a no-brainer. Now, the 99 Lives Cat Genome Sequencing Consortium at the University of Missouri is using whole-genome sequencing (WGS) to identify genetic variants that cause rare diseases, such as progressive retinal atrophy and Niemann-Pick type 1, a fatal disorder in domestic cats. Findings from the new study—published recently in Scientific Reports in an article entitled “Early-Onset Progressive Retinal Atrophy Associated with an IQCB1 Variant in African Black-Footed Cats (Felis nigripes)”—may help feline preservationists implement breeding strategies in captivity for rare and endangered species such as the African black-footed cat.

In the current study, the University of Missouri researchers and 99 Lives Consortium were able to identify a genetic mutation that causes blindness in the African black-footed cat, an endangered species often found in U.S. zoos. Using WGS methods, the investigators sequenced the DNA of three cats—two unaffected parents and an affected offspring—to determine if the mutation was inherited or spontaneous. The genetic mutation identified was located the IQCB1 gene and is associated with progressive retinal atrophy, an inherited degenerative retinal disorder that leads to blindness. The affected cat had two copies of the genetic mutation, indicating that it was an inherited disorder.

“African black-footed cats are closely related to domestic cats, so it was a good opportunity to use the 99 Lives database,” explained senior study investigator Leslie Lyons, Ph.D., professor of comparative medicine, veterinary medicine, and surgery at the University of Missouri. “When sequencing DNA, we are looking for the high-priority variants or genetic mutations that result in disease. Variants in the IQCB1 gene are known to cause retinal degeneration in humans. We evaluated each gene of the African black-footed cat, one at a time, to look for the genetic mutation that is associated with vision loss.”

In an additional study, representing the first time precision medicine has been applied to feline health, Dr. Lyons and her team used WGS and the 99 Lives Consortium to identify a lysosomal disorder in a 36-week-old silver tabby kitten. The kitten was found to have two copies of a mutation in the NPC1 gene, which causes Niemman-Pick type 1, a fatal disorder. The NCP1 gene identified is not a known variant in humans—it is a rare mutation to the feline population.

The results of this study were published recently in the Journal of Veterinary Internal Medicine in an article entitled “Precision Medicine in Cats: Novel Niemann-Pick Type C1 Diagnosed by Whole-Genome Sequencing.”

Identification of both the IQCB1 gene in the African black-footed cat and the NCP1 gene in the silver tabby will help to diagnose other cats and allow them to receive appropriate treatment. Using results of the black-footed cat study, zookeepers will be implementing species survival plans to help manage the cats in captivity in North America.

“Genetics of the patient is a critical aspect of an individual's health care for some diseases,” Dr. Lyons concluded. “Continued collaboration with geneticists and veterinarians could lead to the rapid discovery of undiagnosed genetic conditions in cats. The goal of genetic testing is to identify disease early so that effective and proactive treatment can be administered to patients.”