A horse is a horse, of course, but gray horses have long held special status. Think Shadowfax of the Lord of the Rings or the Lone Ranger's Silver. New research has pinpointed the mutation that causes this prized coloring, a genetic change that may also explain why the animals sometimes die before their darker counterparts.
Gray horses, a broad term that includes animals with white or gray speckled coats, begin their lives a dark gray color and turn pale gray or white by age eight. The color is genetically dominant, meaning horses only need one copy of a hypothetical "gray gene" to become gray, yet the gene itself has remained elusive. Previous research suggested that it might lie in a specific region of chromosome 25. (Horses have 64 chromosomes.)
So a team of Swedish scientists compared the region with the same one in the DNA of nongray horses. In all, the researchers analyzed 727 gray horses and 131 nongrays. They found a duplication of about 4600 base pairs in one gene, called STX17, in all of the gray horses but none of the nongrays, leading them to conclude that the duplication is behind the gray color. The gene has no known function, but the mutation’s presence in all gray horses indicates that the animals had a common ancestor--one that humans probably chose for breeding because of its unique color.
The scientists then turned their attention to life span. By age 15, 70% to 80% of gray horses develop melanoma, a potentially fatal cancer of pigmentation cells in their skin. The team analyzed DNA from gray horse tumors and discovered that STX17--along with a gene located nearby--was more active in the melanoma cells than in the normal gray horse tissue. This difference suggests that the STX17 duplication is involved in both graying and melanoma, though the exact mechanism is unclear, the researchers report online this week in Nature Genetics. Geneticist and team leader Leif Andersson of the University of Uppsala in Sweden speculates that the duplication could cause an overproduction of melanocytes, the cells that are responsible for pigmentation.
Veterinary biologist Bhanu Chowdhary of Texas A&M University in College Station says that more research is needed to understand how the duplication triggers graying and melanoma. But he calls its identification an "important breakthrough," an assessment echoed by horse geneticist D. Philip Sponenberg of Virginia Polytechnic Institute and State University in Blacksburg. The finding is also relevant for human cancers, he says, because the genes expressed in gray horse melanomas are different from those in human tumors. So researchers should not use horse melanoma as a model for the human disease, as some have done, says Sponenberg.
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