"COMPLETE RIDER" YOUR #1 HORSE DESTINATION
The Genetics of Allergy in the Horse
By Dr. Johanna WatsonRepublished with permission from Udavis
Many people are familiar with genetics in "simple" terms where there are two types of genes: dominant and recessive. This is known as the classical Mendelian inheritance patterns. There are many good examples of Mendelian inheritance in our own lives and in the lives of our horses. When we talk about eye color in people, we say that blue eye color is recessive to brown eye color. When we talk about coat color in horses, we say that black coat color is recessive to bay coat color. There are also two good examples of "simple" Mendelian inheritance of disease in horses: hyperkalemic periodic paralysis (HYPP) in Quarter Horses and combined immunodeficiency (CID) in Arabians. These diseases are caused by recessive genes, where one copy of the gene produces a normal appearing carrier of the trait (heterozygous), and two copies produce a diseased individual (homozygous).
Many diseases in humans and horses are not under the simple control of one gene. Instead, they are influenced by a complex group of genes, and do not follow the classical Mendelian inheritance patterns. How many of us know someone who has high blood pressure or heart disease and also has a family history of the disease? Yet, no single gene has been found that can explain the inheritance pattern of high blood pressure or heart disease in these families. One of the major medical challenges of the 21st century is discovering which genes in a complex genetic disease will most likely lead to improved therapies and improved breeding practices in animals.
In humans, allergy is a good example of a complex genetic disorder that is probably caused by the interactions of multiple genes. The idea that allergic disorders have a genetic component dates back to 1916. Two geneticists, Cooke and Van der Veer, found that 50 percent of allergic patients had a positive family history of allergy while in the non-allergic patients, less than 15 percent had a positive family history of allergy. For many years, conflicting studies found allergy to be inherited either as a dominant gene or as a recessive gene. In the 1960s, however, the concept of complex genetics was introduced and allergy was accepted as an example where multiple genes play a role in its development.
If allergy is caused by the interactions of multiple genes, then how do we ever find all the specific genes? Researchers use two types of studies to develop lists of involved genes. The first approach is to analyze the entire genetic code in very large numbers of people (called genome-wide scans) to identify connections or linkages between sections of chromosomes or loci, and the development of allergic asthma. The second approach (candidate gene approach) involves selecting a gene that is likely to be involved (an educated guess) and then studying people or animals with and without disease to support that gene's involvement. What is truly exciting is that the two types of studies, conducted independently, have come up with remarkably similar "laundry lists" of genes. Now, it is important to start looking at each of the candidate genes to discover just how much influence each gene has on the development of allergy. Once researchers learn about the genetic events that contribute to the development of allergies and asthma, then they will have a better understanding of the diseases and their treatment.
How does this all get back to the horse? Most likely, the disease process of allergy in humans is very similar to that in the horse. Therefore, we can use the same "laundry list" of candidate genes to begin our own studies of the genetic control of allergic disease in the horse. While allergic disease is certainly under the control of many genes, there is one gene that has at least three known "types" or alleles in humans, and these alleles appear more commonly in allergic people. This gene, the interleukin-4 receptor, is a cell surface receptor for a major cell message called interleukin-4. Interleukin-4 is released from cells to tell other cells in the neighborhood about an invader or foreign protein. This signal is released in the face of a parasitic infection. The signal binds to the interleukin-4 receptor on local cells and brings about important changes in the local cells to combat parasites. Cells receive messages through receptors. You can think of the receptor as a telephone -- if the telephone is broken, the cell doesn't get the message; if the phone rings all the time, the cell may over-react.
The interleukin-4 receptor (IL4r) gene may play a major role in the development of allergic disease in humans, horses and other species. To investigate the role of IL4r in the horse, researchers need four tools: 1) interleukin-4 from the horse, 2) the IL4r gene's sequence in the horse and a test to detect it, 3) a cell type from the horse that has the IL4r on its surface, and 4) an indicator of IL4r function that can be measured. With funding from the Southern California Equine Foundation, our laboratory now has all these tools available.
Dr. David Horohov from Louisiana State University kindly provided our laboratory with a source of equine IL4 that he developed. Using a test based on the IL4r's DNA sequence, we found that equine macrophages are a good cell type to test for IL4r function. Macrophages, meaning "big-eaters," are large cells responsible to defend the body from invaders. These cells can be obtained in large numbers from living horses. Using a test based on the DNA sequence of CD23, a protein produced in response to IL4, we found that macrophages signaled by IL4 made large amounts of CD23.
We suspect that there are a number of equine diseases caused by allergy, including two respiratory diseases of performance horses: inflammatory airway disease and chronic obstructive pulmonary disease (COPD). Historically, veterinarians have used two types of testing on horses to diagnose allergic disease: skin testing for reactions to specific allergens and blood testing for circulating immunoglobulins (IgE) against specific allergens. Both of these tests are difficult to interpret when run on animals who are not showing signs of allergic disease at the time because all horses, even normal horses, show some positive reactions on both test types. Additionally, neither of these tests is specific for respiratory allergy. We anticipate that our studies of equine CD23, a cellular marker of interleukin-4 activity, will yield a test for the early detection of respiratory allergy in the horse.
If veterinarians could identify horses affected by respiratory allergy early on, they could provide the horse owner with information he/she could use to determine whether to invest the costs of training in those horses with respiratory allergy. Therapeutic intervention could be attempted earlier in the course of the disease, perhaps preventing permanent lung damage. The next logical step to prevent economic losses due to allergic disease is to develop a genetic test for the condition. While allergic disease is certainly under the control of many genes, we believe that the interleukin-4 receptor is a promising candidate gene. We anticipate that ongoing studies of this candidate gene in the horse will potentially lead to the development of a test to screen horses for the predisposition to allergic disease.
>>Archives
Dr. Johanna Watson
E-Mail info@completerider.com
Features|Health|Nutrition|Horse Power|Horse Sport|Horseman|Canadian Thoroughbred|Horse News|
TV Show|Horse Play|Learning Center|Sale Horses|HorsE-Shop|Contact Us| Advertise|
designed for grasslands entertainment group by webSlave Mara all rights reserved
