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
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. (Am J Vet Res 2000;61:462–468)