Inheritance of gluten-sensitive enteropathy in Irish setters

Objective-To establish a model for inheritance of gluten-sensitive enteropa thy (GSE) in Irish Setters. Animals-44 dogs of a 6-generation family of Irish Setters with GSE and 7 he althy Irish Setters. Procedure-Phenotype of each dog was determined after oral administration of gluten in the weaning diet, using morphometric evaluation of jejunal biops ies (all generations) and measurement of small intestinal permeability by u se of a lactulose-rhamnose permeation test (generations 1, 2, and 3). Overa ll probability for each of 4 genetic models of inheritance (autosomal reces sive, autosomal dominant, sex-linked recessive, and sex-linked dominant) ac counting 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-lin ked models were untenable. These conclusions were robust to the error attac hed to estimation of disease prevalence. High intestinal permeability witho ut morphometric jejunal abnormalities in 4 of 20 dogs in the 3 youngest gen erations suggested heterogeneity of lesions associated with GSE. Conclusions-Genetic transmission of GSE is under the control of a single ma jor autosomal recessive locus.