Inheritance of gluten-sensitive enteropathy in Irish Setters

OBJECTIVE: To establish a model for inheritance of gluten-sensitive enteropathy (GSE) in Irish Setters. ANIMALS: 44 dogs of a 6-generation family of Irish Setters with GSE and 7 healthy Irish Setters. PROCEDURE: Phenotype of each dog was determined after oral administration of gluten in the weaning diet, using morphometric evaluation of jejunal biopsies (all generations) and measurement of small intestinal permeability by use of a lactulose-rhamnose permeation test (generations 1, 2, and 3). Overall probability for each of 4 genetic models of inheritance (autosomal recessive, autosomal dominant, sex-linked recessive, and sex-linked dominant) accounting for segregation of partial villus atrophy within the entire family was calculated. RESULTS: The autosomal recessive model was most tenable and was 56,250 times more likely to account for segregation of partial villus atrophy than the autosomal dominant model, assuming disease prevalence of 0.8%. Both sex-linked models were untenable. These conclusions were robust to the error attached to estimation of disease prevalence. High intestinal permeability without morphometric jejunal abnormalities in 4 of 20 dogs in the 3 youngest generations suggested heterogeneity of lesions associated with GSE. CONCLUSIONS: Genetic transmission of GSE is under the control of a single major autosomal recessive locus.