Chronic intestinal disease that is associated with the loss of protein into the gut, termed protein losing enteropathy (PLE), is a severe, life threatening condition that affects many dog breeds, including Yorkshire Terrier, Soft-coated Wheaten Terrier, Basenji, Norwegian Lundehund, and Chinese Shar-pei. The syndrome of PLE is most common in Yorkshire Terriers (4.2-10 fold relative risk) and affected dogs frequently suffer from severe weight loss, accumulation of fluid within tissues and body cavities, diarrhea, low levels of circulating proteins, increased risk for abnormal clotting, and derangements in vitamin and mineral homeostasis. The microscopic appearance of the small intestine of Yorkshire Terriers with PLE (YT-PLE) is distinct from PLE in other breeds, suggesting that it is caused by a breed-specific genetic abnormality. Despite aggressive treatment remission is variably achieved, and relapse is common. Long-term survival is infrequent, with recent studies indicating treatment failure in @50% of Yorkshire Terriers with PLE. The high morbidity and mortality of YT-PLE indicates the need to eradicate this disease through informed breeding. It is against this background that we are seeking to identify genetic regions and genes associated with YT-PLE to enable prevention of this disease, provide insights into the development of PLE across-species, and facilitate the discovery of more specific and effective therapies. Preliminary studies in our laboratory have linked several genetic regions to YT-PLE but additional genotyping of DNA samples from YT with and without PLE is required to enable definitive identification of causal abnormalities.