Can cat genes explain their nine lives?

Move over human genomic medicine – scientists are now getting closer to gene therapy for felines, thanks to an Abyssinian cat called Cinnamon. Her DNA sequence was used for the first-high quality version of the cat genome, described in the journal PLOS Genetics.

Using it as a reference, researchers compared it to a database of published genes from 54 cats gathered by the 99 Lives Cat Genome Project to find mutations that could help solve the mystery of heritable diseases in felines.

A key finding was a new mutation likely responsible for feline dwarfism, according to lead author Reuben Buckley, who did the work at the University of Missouri, US. The mutation, a “structural variant”, was found in the UGDH gene which has not previously been associated with dwarfism in any species.

This could shed light on human dwarfism, says Buckley. “Ultimately, this result indicates how genomics in non-human animals can help deepen our understanding of gene functions in humans.”

The domestic cat (Felis catus) is prone to many of the same diseases as its human companions. Cat lovers may be happy to know that genomics might help vets detect and treat diseases.

So far, researchers have found mutations that could be responsible for bobbed tails, ear curl and inherited blindness in Bengal and Persian cats. The genomes of cats with eye diseases gave insights into the cause and possible treatments for similar conditions in humans.

Other diseases researchers are studying with a possible genetic link include diabetes, cancer and heart disease.

Recent advances in DNA sequencing have made it more affordable for scientists working on species other than humans and mice to develop high-quality reference genomes using a technology called long sequencing.

This is important, says Buckley, because it could help scientists separate benign from pathogenic mutations.

Collecting DNA from their furry volunteer Cinnamon, his team used long-read technologies to put her genome together. They produced 10-times more fragments than previous technologies, improving the accuracy of the sequence.

“For example, imagine solving a jigsaw puzzle of 100 large pieces and a jigsaw puzzle of 1000 small pieces,” Buckley explains. “The assembled jigsaw puzzle made of 100 pieces is far less likely to contain assembly errors than the puzzle made of 1000 very small pieces.”

The study revealed that cat gene mutations accumulate in a similar manner to variants in human genes, suggesting genetic information can help inform impacts of mutations across species.

They also found that an individual cat genome carries millions more variants than a human genome and was also markedly higher than those found in studies of other mammals including dogs, rats, horses and rhesus monkeys.

Could this help explain why cats seem to have nine lives? It might help them tolerate this increased mutation burden, says Buckley, although it’s doubtful because most of them occur outside gene regions and are benign.

It might have something to do with the fact that cats were originally “self” domesticated, the authors suggest, continuing some of their ancestors’ behaviours such as hunting.

This characteristic independence doesn’t stop people loving them; according to Buckley’s mentor and co-author Leslie Lyons, “Cats rule, dogs drool!”. Not him, though, he says. “I prefer genomes.”

The Royal Institution of Australia has an Education resource based on this article. You can access it here.

Related reading: In cat breeds, behaviour is inherited