A Cornell veterinary immunologist and one of his research mares are at the center of the sequenced horse genome, which may turn out to be the most important breakthrough for horses since the advent of the horseshoe some 2,000 years ago. Twilight -- who was bred, born and raised at Cornell's McConville Barn -- was the sole DNA donor for the entire horse genome, which was fully sequenced in 2006 by the Horse Genome Project. The 2.7 billion DNA base pair sequence is analyzed in the Nov. 6 issue of the journal Science.

Doug Antczak, the Dorothy Havemeyer McConville Professor of Equine Medicine in the Veterinary College's Baker Institute for Animal Health, is an author on this landmark equine research paper. Antczak has been a prominent participant in the international, multidisciplinary Horse Genome Project team since its inception in 1995. Twilight is a member of a small herd of horses bred specifically for the makeup of their histocompatibility genes. These genes are under study in the Antczak laboratory for their role in protection against infectious disease and in maternal tolerance to the developing fetus in pregnancy.

The new Science article documents that the arrangement of genes on individual chromosomes is very similar in horses and humans, a pattern that will assist researchers in using insights from one species to illuminate the other. The study's authors note that horse population history has led to important genetic similarities across horse breeds, increasing the feasibility of across-breed mapping as well.

"The horse genome sequence is changing equine research and clinical medicine fundamentally and completely," said Antczak, who noted that it also promises insights for human medicine. "Researchers in many areas are rapidly adopting this technology, and those who are not using it may soon find themselves behind the times."

Genome mapping has already enabled the development of genetic tests for about 10 simple inherited genetic diseases, including severe combined immunodeficiency disease of Arabian horses, lethal white of paint horses, and hereditary equine regional dermal asthenia and hyperkalemic periodic paralysis in quarter horses. Genetic testing for these single-gene disorders, some of them fatal, is becoming standard practice for certain horse breeds and may soon eradicate these conditions, Antczak said.

Another highly promising application of the horse genome is the development of miniature devices (expression arrays) that contain probes for all of the 20,000-plus genes of the horse on chips that can be used to profile gene activity across the genome, illuminating unknown functions and mechanisms of normal physiology and disease. Such profiling may one day produce breakthroughs in areas as diverse as lameness, lung disease, reproduction and immunology, Antczak noted.

For example, at the College of Veterinary Medicine, Alan Nixon, professor of large animal surgery and director of the Comparative Orthopedics Laboratory, is using equine expression arrays to investigate osteochondritis dissecans, a common and debilitating cartilage disease in growing animals and children. Dorothy Ainsworth, professor of large animal medicine, is utilizing the technology to study equine chronic lung disease. And Tracy Stokol, assistant professor of clinical pathology, plans to apply the expression array developed in Antczak's laboratory to study aspects of equine herpes virus disease.

Dan Gurvich, a special assistant to the dean for strategic initiatives in the College of Veterinary Medicine, is a contributing writer for college publications.