Breaking The Code Of Dog & Human Genetics

| October 22, 2014 | 0 Comments
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Disheartening as it may be when a dog is diagnosed with a genetic disease, particularly one that also occurs in people, knowledge about the disease may help advance understanding. Here is a glimpse of studies that may one day help reduce canine histiocytic sarcoma, calcium oxalate stones and atopic dermatitis. Cancers that occur in people and in dogs often capture the attention of scientists at the National Human Genome Research Institute (NHGRI) in Bethesda, Maryland. Such is the case with histiocytic sarcoma, a rare, highly aggressive cancer in people that is often seen in Flat-Coated Retrievers and Bernese Mountain Dogs. “The high frequency in Flat Coats and Bernese Mountain Dogs provides an unparalleled model for studying the human cancer,” says Heidi G. Parker, an NHGRI scientist who is leading the research. “Our findings about affected genes and pathways in dogs will provide valuable information to human oncology.” Histiocytes are leukocytes, or white blood cells, that have an immune function role to protect the body. When the cells become cancerous, they invade and destroy surrounding tissues. Histiocytic sarcoma frequently metastasizes to multiple organs, such as the spleen, lymph nodes, lung, bone marrow, and skin. In people, histiocytic sarcoma is diagnosed in children nearly as often as it is found in adults, with survival ranging from two to 10 months. In dogs, the average age of onset is 6 to 8 years, though diagnoses have been made in dogs as young as 1 year old. The cancer is difficult to detect at early stages because of the ambiguity of the signs, which include anorexia, weight loss and decreased energy. To learn about what causes the cancer, the NHGRI scientists conducted a genome-wide association study of samples from 204 Flat-Coated Retrievers and 466 Bernese Mountain Dogs, comparing those diagnosed with histiocytic sarcoma to older cancer-free dogs. “Our hypothesis is that there are two distinct subtypes of histiocytic sarcoma in dogs,” Parker says. “We believe our work will lead to more effective therapies for both people and dogs, and a genetic test to identify dogs that carry the mutations leading to cancer.” Owners of Flat-Coated Retrievers and Bernese Mountain Dogs diagnosed with histiocytic sarcoma, as well as cancer-free dogs age 10 and older, may submit blood samples for the NHGRI study. For information contact Erica Chapman, samples manager, at erica.chapman@nih.gov or 301-451-9390.

Zinc & Calcium Oxalate Stones The possibility that a gene involved in zinc transport causes calcium oxalate (CaOx) stones in dogs may lead to new treatments for the most common type of canine urinary stone. Scientists at the Univer­sity of Minnesota College of Veterinary Medicine in St. Paul believe that mutations in the gene increase the risk and thus contribute to the prevalence of CaOx stones in certain breeds. “Calcium oxalate stone disease is complex,” says Eva Furrow, V.M.D., Ph.D., DACVIM, assistant professor. “Multiple genetic and environmental factors influence the risk of developing stones.” A painful, recurring condition, calcium oxalate stones are highly prevalent in the Miniature Schnauzer, Bichon Frise and Shih Tzu breeds among others. Miniature Schnauzers have 12 to 22 times the risk of a mixed-breed dog for developing stones. Furrow and her colleagues conducted a genome-wide association study to compare the genetic profiles of 62 CaOx stone-forming Schnauzers with 41 stone-free Schnauzers. They identified on canine chromosome 37 variations in the SLC39A10 gene that is involved in zinc transport. “We found variants in a renally and intestinally expressed transmembrane solute carrier in the stone-forming dogs,” Furrow says. “It could be that abnormal processing of zinc in the body directly increases the risk for stones or that the abnormal zinc transport indirectly alters calcium transport.” The scientists recently began studying the genetics of the disease in the Bichon Frise and Shih Tzu. Owners of Miniature Schnauzers, Bichon Frise and Shih Tzu with a history of forming calcium oxalate stones may contribute blood samples or cheek swabs to support the genetic research at the University of Minnesota. For information, contact Furrow at furro004@ umn.edu. For more information about the research, visit: http://cvm.umn.edu/vgs/faculty/Mickelson/lab/CalciumOxalate/html.html

A Candidate Gene for Dermatitis Atopic dermatitis is a miserable, incurable disease that occurs in dogs and people. A genetics study by scientists at Uppsala University in Sweden has begun the search for mutations that increase the risk for the skin disorder in German Shepherd Dogs. “Genetic and environmental factors contribute to this disease,” says Katarina Tengvall, MSc, a doctorate student in genetics at Uppsala University. “We have found that affected German Shepherds have lower blood immunoglobulin A (IgA) levels. Low levels of IgA are often accompanied by recurrent infections and autoimmune and allergic diseases just as in humans with IgA deficiency.” The connection between low IgA levels and affected German Shepherd Dogs may be unique to the breed because in some other breeds there is no correlation between atopic dermatitis and low IgA levels. “In German Shepherds, the correlation is pronounced,” Tengvall says. Although the study focuses on German Shepherd Dogs in Sweden, the American breed also develops atopic dermatitis. Differences may vary between subpopulations within a breed, as was found in the Swedish German Shepherd Dogs, where subtypes of the breed show differences in prevalence rates. Despite not being a fatal disease, atopic dermatitis is a lifelong condition that requires veterinary care and owner compliance. The Uppsala scientists conducted a genome-wide association study of 91 affected German Shepherds and 88 control dogs and found an association between the disease and canine chromosome 27 in the plakophilin 2 gene, which is important for skin structure. “We are following up on these findings in multiple breeds,” Tengvall says. “We have an excellent novel candidate gene for atopic derma­titis in dogs and humans. In the future, we hope to provide guidance to dog breeders on both breeding and health care.”

Purina: A Leading Sponsor Much of the information in this article is from talks presented last fall in Boston at two global genetic conferences, both of which Purina has sponsored since their beginnings. The seventh biennial International Conference on Advances in Canine and Feline Genomics and Inherited Diseases was attended by geneticists, and the sixth Tufts’ Canine & Feline Breeding & Genetics conference was open to dog and cat breeders as well as geneticists.

Breeding with a Vision Successful breeders have a plan. They can tell you today which dogs they plan to breed together to produce their next two or three litters. “Breeding requires a vision,” says Anita Oberbauer, Ph.D., professor and chair of the Department of Animal Science at the University of California-Davis. “You must define your objectives and goals, and determine the ‘must haves’ and the acceptable ‘trade-offs.’ The hallmark of a good breeder is making progress toward the overall objectives and minimizing the negative impact of the trade-offs.” Breeders generally select breeding partners based on how individual dogs are likely to contribute to their goals. “You should select for the most important traits. The more traits that are undergoing selection, the less selective pressure that can be applied to any single trait,” explains genetic counselor Jerold Bell, D.V.M., clinical associate professor of veterinary genetics at Cummings School of Veterinary Medicine at Tufts University. It is estimated that less than 5 to 20 percent of a breed produces the next generation. Selection for quality and maintaining different bloodlines are important to preserve breed health and genetic diversity. The ability to balance positive traits and deleterious genes is fundamental to breeding. Healthy bloodlines, and healthy breeds, start with a vision to see how to accomplish these goals.

Mix Up Your Breeding Genetic experts advise dog breeders to always strive to produce quality, healthy dogs. Using different types of mating tools will help mix breeding lines and maintain genetic diversity. For example, consistently relying on outbreeding removes the differences between dogs and thus reduces the ability to select for individual traits. Here are mating tools that can help you achieve genetic diversity.

  • Outbreeding is a mating between dogs less related than the average for the breed. It should be used to bring in traits that a particular dog does not have.
  • Linebreeding is a mating between dogs more related than the average for the breed. It should be used to solidify the traits in your bloodline.

Smart Breeding

  • Healthy and diverse breed gene pools have expanding or large stable populations with many outbred clusters as well as different linebred families.
  • Avoid the overuse of popular sires, the single most influential factor in restricting breed gene pool diversity.
  • Parent clubs should regularly conduct breed health and reproduction surveys to assess breed health.
  • Select against recessive disease genes by breeding quality carrier dogs to a tested normal mate. Replace the carrier parent with a quality tested normal offspring for breeding. This eliminates the defective gene, while maintaining the quality genes of the line.

Category : Health

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Purina® Pro Club® has hundreds of articles in their ever-expanding library on dog and cat nutrition, genetics, health and training, covering breeds from Afghans to Wirehairs and everything in between.

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