Description: Cleft palate (CP) is one of the most common craniofacial birth defects in humans. The Nova Scotia Duck Tolling Retriever (NSDTR) dog breed with a naturally occurring cleft palate was used as a model system in the study. The clefts of the hard and soft palate are a hole in the palate created during the development of the puppy. Puppies are born with a cleft palate. A cleft lip is a split in the lip and can occur on one or both sides of the mouth. Other craniofacial abnormalities include uneven alignment of the upper jaw and lower jaw, missing or poorly developed nasal septum, abnormal angle of the mandibular head of the condylar process, or general asymmetry of the entire craniofacial complex. We refer to this phenotype in NSDTR as CP1. A genome-wide association study (GWAS) revealed a region of candidate genes (DLX5 and DLX6) and subsequent sequencing identified a 2.1 kb LINE-1 insertion in DLX6 in NSDTR dogs with cleft. LINE-1 insertion is predicted to result in a premature stop codon in the DLX6 homeodomain.

Not all cases of cleft palate were attributable to LINE-1 insertion in DLX6, indicating not only phenotypic but also molecular heterogeneity. Subsequent GWAS found that the NSDTR breed has several genetic causes of cleft palate.

Syndactyly, which is a fusion of the middle two toes, occurs along with the cleft palate. Recently, a mutation in the ADAMTS20 gene has been identified that causes a second form of cleft lip and palate called CLPS.


Inheritance: autosomal recessive


Mutation:  2.1 kb LINE-1 insertion in DLX6


Sample: EDTA whole blood (1.0 ml) or 2 buccal brushes


The analysis is suitable for the following breeds: Nova Scotia Duck Tolling Retriever (NSDTR)


Notes: The analysis is only for NSDTR breed. Another mutation c.1360_1361delAA (p.Lys453Ilefs*3) in ADAMTS20 gene cleft palate, see CLPS.