Prediction of inherited portosystemic shunts in Irish wolfhounds on the basis of pedigree analysis

Objective-To test validity of prediction for inherited portosystemic shunts (PSS) in Irish Wolfhounds, using nonselective clinical findings and a comp uterized database containing 5-generation pedigrees. Animals-613 dogs in the first and 396 dogs in the second cohort. Procedure-Preprandial venous ammonia concentration was measured at 6 to 8 w eeks in all pups born between Jan 1, 1988 and Jan 1, 1997. Portosystemic sh unts were confirmed in hyperammonemic pups, using radioisotope shunt index measurement, and diagnosis of shunting was confirmed at abdominal surgery o r necropsy. Findings in dogs of the first cohort (born before Jan 1, 1992) were used to predict shunting in their offspring of the second cohort. Comm on ancestors of first-cohort dogs with shunts were tested for positive asso ciations with the disease. Risk for a shunt in all second-cohort dogs was p redicted on the basis of relatedness with founders and was compared with ou tcome of clinical screening. Results-Prevalence of shunts in first and second cohorts was 3.1 and 2.3%, respectively. Fifteen highly related associated founders could be identifie d. Second-cohort dogs were classified into 6 groups of increasing predicted risk. Mean number of dogs per class was 60; number of clinically diagnosed cases ranged from 0 in the class with the lowest risk to 4 in the highest risk class. Conclusions-Genetic risk for reproducing a PSS in Irish Wolfhounds was accu rate, using the described method. Clinical Relevance-Risk estimation provides a tool for genetic counseling, does not require knowledge of the mode of inheritance, and may be valid for any inherited disease.