Genomics is probably a lot like the invention of airplanes. My grandfather was born before the invention of manned flight and died years after the moon landings. I once asked what he thought of flight, and he told me flying was just a great way to get from one place to another. Clearly he took it for granted. If we had discussed genomics, I suspect he would have asked, "What's it good for?"
Genomics (the study of all the genetic material within an organism) has revolutionized genetics for horses. I am impressed, but my students have another perspective. My first-year students were born after the beginning of the human genome project (1990) and were toddlers when we began the Equine Gene Mapping workshop (1995). Rather than having awe for genomics, my students consider DNA tests for coat colors and hereditary diseases to be just plain sensible. No big deal! What's next? Certainly we have more tests to develop. But frankly, coat color tests are to genomics what wing-walking was to early flight--trivial expressions of an amazing technology.
Dr. Balasuriya and student Yun Young Go (above) are helping wed virology, genetics, and genomics.
We do not usually think of genetics and genomics in connection with infectious diseases; however, one of the greatest applications of horse genomics will be for preventing equine infectious diseases. Until now, most infectious disease research focused on the pathogen. There can be no question but that isolating and identifying the pathogen was, and is, of primary importance: When pathogens are found to stimulate the immune system, vaccines might be developed. With the pathogen in hand, scientists can investigate susceptibility to antibiotics or other chemical
therapeutics. However, the key piece of information needed to help horses fight disease is to know how horses respond to the pathogen. Until the advent of genomics, we could not effectively investigate horses' complex response to infection or the tricks pathogens use to evade that response.
Vaccination protects our horses from several serious infectious diseases; however, we have been unable to produce effective vaccines for many diseases. For example, our equine herpesvirus vaccines only produce short-term immunity; equine herpesviruses have evolved a way to block development of long-term protective immunity. Influenza viruses use another strategy. Vaccines for influenza are effective, but only for the strain used to make the vaccine; influenza viruses evade the immune system by rapidly evolving a new genetic and antigenic (producing new virus strains) profile unrelated to that vaccine.
Likewise, antibiotics are a special tool for fighting bacterial infections, but bacteria are becoming resistant to many antibiotics. Despite antibiotics' ability to kill billions of bacteria, the few that are genetically resistant have replaced the susceptible, rendering antibiotic treatment equivocal in some cases.
Genomics will provide new strategies to fight infectious disease that don't rely on vaccines or antibiotic treatments. The goal will be to discover the tricks pathogens use to evade the immune system. Recently, Udeni Balasuriya (BVSc, MS, PhD) and graduate student Yun Young Go, at the University of Kentucky's Gluck Equine Research Center, were the first to wed equine virology, genetics, and genomics in a study about equine arteritis virus (EAV), which causes respiratory disease, abortion in mares, and can establish a persistent infection in the male reproductive tract. These stallions become natural sources of EAV and continue to shed the virus in their semen. Go and Balasuriya discovered that EAV infected a subpopulation of white blood cells in some horses but not others. This difference also appeared to play a role in disease severity. They used genomics to demonstrate that the trait was hereditary and identified the chromosome location of genes responsible for disease severity and development of the carrier state. This work will lead to new EAV prevention and treatment approaches.
Genomic studies are under way for other equine infectious diseases. In some cases we will uncover ways to enhance horses' ability to fight infection, including ways to improve vaccinations. In other cases we will uncover and foil pathogens' molecular tricks. Genomics is in its infancy, and we have a lot to learn. But have no doubt, its impact on equine infectious diseases will be as great as that of vaccination and antibiotics.
Ernest Baily, PhD, specializes in immunogenetics and genomics at the University of Kentucky's Gluck Equine Research Center in Lexington.