Cleft Lip and/or Palate With Monogenic Autosomal Recessive Transmission in Pyrenees Shepherd Dogs

Objective: To document the genetic background of Pyrenees shepherd dogs as it relates to the incidence of cleft lip and/or cleft palate, to describe the phenotype, and to determine possible candidate genes. Design: Pedigree analysis was performed and blood samples were taken from five affected pups, their siblings, and parents. Seven candidate genes were selected and linkage analysis was performed. Further methods used included sequencing and histology. Results: In 37 litters consisting of 163 pups, we found 47 affected pups in a total population of 2104. The male:female ratio was 1:0.96. Affected pups showed isolated cleft lip and/or cleft palate; no attendant disorders have been reported. Despite a high degree of relationship, two affected pups displayed a cleft palate (- H S H -) and a cleft lip with or without cleft palate (L A -) cleft formation. Histology of affected pups showed that the medial edge epithelium remained intact and did not undergo an epithelial-mesenchymal transformation. There was no evidence for linkage between the trait and TGFb3 or Msx1. Subsequent sequencing excluded the coding sequence of Fst as well. Conclusion: Pedigree analysis showed that cleft palate is not genetically distinct from cleft lip with or without cleft palate but is inherited in this breed as a monogenic autosomal recessive trait. Linkage analysis and sequencing excluded TGFb3, Msx1, and Fst as candidate genes. Histology of affected pups showed that the medial edge epithelium is still intact.