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How the cat got his blotches

As any cat lover knows, distinct patterns of dark and light hair color are apparent not only in housecats but also in their wild relatives, from cheetahs to tigers to snow leopards. Researchers at the HudsonAlpha Institute for Biotechnology and Stanford University, along with colleagues around the world, today reported new genetic findings that help to understand the molecular basis of these patterns in all felines.

A so-called "mackerel tabby" cat has dark tiger stripes, which coalesce into swirls and blotches in a "classic tabby" cat. Like other periodic natural patterns such as stripes on a zebra or spinal bones and vertebra, the origin of these repetitive structures is an unsolved mystery. "Until now, there's been no obvious biological explanation for cheetah spots or the stripes on tigers, zebras or even the ordinary house cat," said Gregory Barsh, M.D., Ph.D., faculty investigator at HudsonAlpha and emeritus professor of genetics at Stanford University, one of the senior authors of the study.

When comparing sequence differences between striped and blotched domestic cats, the researchers saw the evidence pointed to a gene that they named Taqpep. Blotched cats had specific mutations in both copies of this gene, while striped cats did not. Remarkably, the rare "king cheetah," once thought to be a unique species because of an unusual striped pattern rather than regular spots, also carried a mutation in Taqpep.

The team then went on to ask how spots, stripes or blotches form in the first place. "Somehow, cells in the black stripes know they are in a black stripe and remember that fact throughout the organism's life," said Barsh. "We were curious about what's happening at the boundary between light and dark stripes and spots. How do these spots know to grow with an animal?"

Their examination of genes expressed in dark versus light hair cells revealed that patterned markings are due to variations in another gene, Edn3, being expressed at high levels in the darkly colored hair cells. The researchers thus suggest that the Taqpep gene helps to establish either a periodic pattern for stripes or a spotted or blotched pattern, by determining the level of Edn3 expressed in each skin area at an early stage of the cat's development.

According to Barsh, discovery of new genetic pathways and mechanisms is the foundation for understanding the blueprint encoded in any genome, including humans. Studies with fruit flies and roundworms have revealed principles that govern how cancer cells live and die, he noted. "Uncovering new biologic principles in animals that are more closely related to humans, like cats, dogs and laboratory mice, may reveal unexpected insights with far-reaching implications for human biology and disease," he added.

Next up for the group: figuring out the exact mechanism by which Taqpep and Edn3 function, and looking at why some animals like lions, cougars, and the Abyssinian breed of domestic cat, don't have noticeable patterns regardless of their Taqpep status. "We know there's a mutation that suppresses pattern formation in some cats," said Barsh. "We'd like to investigate that mechanism as well."

Contact: Holly Ralston or Chris Gunter
HudsonAlpha Institute for Biotechnology

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