The Equine Genome: What it Means for the Future of Horse Health
The National Human Genome Research Institute announced the first
assembly of the completed horse DNA sequence on Feb. 7, 2007. Why would
a human health agency perform DNA sequencing on a horse? The answer is
that the genetic structure and function of all mammals are similar. The
best way for scientists to understand human DNA sequences is to compare
the genome sequence from 24 different mammals to see what DNA sequences
are so important as to be present in all species.
Fortunately, from the perspective of the equine industry, the horse was
chosen as the representative from Perissodactyla, a small order of
hoofed mammals constituting three families-Equidae, Tapiridae and
Rhinocerotidae. This was no small matter. Some biologists had very good
reasons to advocate sequencing other members of the order, such as
rhinos, tapirs and zebras. But we have a large community of scientists
interested in using the horse genome sequence for improving the health
and welfare of horses.
Genome is a new word. What does it mean? /Genetics/ is the study of one
gene at a time. Horses and other mammals have roughly 20,000 to 25,000
genes. When we consider /all/ genes, we call that set a /genome/ and its
study /genomics/. Since genome organization is similar among all
mammals, information from human medical studies helps us to better
understand horse diseases. We have long used humans as a model for
equine diseases, so this approach is nothing new. Nevertheless, genomics
will benefit equine health research as profoundly as vaccines,
antibiotics and radiographs.
Some horsemen may worry that once the horse genome is sequenced, all the
mystery and magic will be gone from horse breeding and ownership.
Colorful characters around a racetrack may be replaced by colorless
scientists with computer printouts and test tubes. Fear not! The study
of the horse genome is more like studying the weather than inventing a
sports car. Consider the following. All of the research on weather has
shown we can experience a sunny day in Florida, knowing that a hurricane
will arrive in two days, but we cannot change the hurricane. Still the
knowledge allows us to make choices; when the hurricane approaches, we
can abandon our town or we can shore up its foundations. Successful use
of genomic tools will help horse breeders, veterinarians and horse
owners do what they already do even better ... anticipate problems,
predict outcomes and enjoy the unique interaction between horses and people.
Even before the horse genome was sequenced, DNA tests had been developed
for inherited diseases of horses as well as many coat color patterns. So
far, breeders can test horses and determine the chances of transmitting
genes for the following disease traits to their offspring: hyperkalemic
periodic paralysis of Quarter Horses (HYPP), severe combined
immunodeficiency disease of Arabian horses (SCID), overo lethal white
foal disease of paint horses (OLWFD), junctional epidermolysis bullosa
of Belgian horses (JEB), glycogen branching enzyme deficiency of draft
horses (GBED), and hereditary equine regional dermal asthenia of Quarter
Horses (HERDA). In the near future, we may have the genes for other
simple hereditary diseases identified.
Color genetics also has improved from the availability of these new
tools. Genetic tests are available for black/chestnut (MC1R), bay/black
(ASIP), cream dilution (MATP), Frame overo (OLWFD), sabino 1 (KIT) and
tobiano (KIT). The acronyms in parentheses refer to the actual genes
involved in these conditions. Although the gene has not yet been
identified for these particular colors, mapping studies have localized
the genes for gray, Appaloosa, dominant white and roan.
As athletic working animals, horses have been selected for health and
performance over thousands of years. Consequently, horses have few
purely genetic diseases. The real benefit of genomics for horses will be
to understand complex diseases that have frustrated horse owners and
veterinarians since the time of domestication. These conditions affect
the musculoskeletal system (osteoarthritis, tying up, contracted foals,
osteochondrosis, navicular disease, laminitis, congenital limb
deformity), allergic diseases, respiratory diseases (recurrent airway
obstruction, heaves, exercise-induced pulmonary hemorrhage) and
infectious diseases (vaccine development for viruses and bacteria).
Why do these problems exist for a species highly selected for health and
performance? We don't know. It may be related to the complex interplay
of genes and our social needs. Sometimes it can be inadvertent. For
example, hyperkalemic periodic paralysis in Quarter Horses is caused by
a single change in a DNA molecule that disrupts potassium metabolism in
muscle cells. The muscles undergo spontaneous and aberrant contractions,
similar to isometric exercises, resulting in a muscular appearance.
Unfortunately, such horses may collapse under the stress of muscular
exertion. We expect that selection for large muscling in Quarter Horses
led to selection for the HYPP gene. Likewise, selection for small size
in miniature horses may inadvertently lead to selection for genes
causing dwarfism. The point is to understand the interplay of genes and
management, then allow breeders and horse owners to continue doing what
they have always done, while making informed choices.
The horse genome sequence is going to accelerate research and save
hundreds of thousands of research dollars. Before now, many scientists
would begin projects by spending months cloning and sequencing DNA for
the gene of interest. When the horse gene was entirely unknown,
scientists would use information from humans, mice or rats to provide a
"best guess" starting point. Now, with the whole genome sequence, anyone
with access to the Internet can circumvent this tedious spadework. The
availability of this information means that one does not need to be a
molecular geneticist to use the information. We anticipate successful
research projects and solutions for the most important diseases of
horses during the next couple of years using the tools derived from this
work.
Breeders and horse owners always want to know how to get the most
enjoyment out of their horses. This information will allow us to fashion
management practices and veterinary care to keep these horses healthy
and performing. The horse genome sequence is going to have an impact on
health as significant as the discovery of radiographs, antibiotics and
vaccines in previous centuries.
Several foundations and universities have initiated equine genetic
research. The Morris Animal Foundation is sponsoring an Equine
Consortium for Genetic Research grant, involving 32 collaborating
researchers from 18 academic institutions. The sequenced horse genome
will be used by the researchers to study and identify those genes and
mutations that contribute to heritable diseases, such as musculoskeletal
disease, laminitis, recurrent airway obstruction and bone disease. Other
funded research by the American Quarter Horse Foundation and
Grayson-Jockey Club Research Foundation support grants for a variety of
investigations into gene response to disease.
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