OMIA 001919-9615 : Cleft palate 1 in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 261800

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2014

Species-specific symbol: CP1

Mapping: From a GWAS conducted on 14 affected and 72 normal Nova Scotia Duck Tolling Retrievers, each genotyped with the Illumina CanineHD BeadChip (yielding 109,506 informative SNPs), Wolf et al. (2014) mapped this disorder in this breed to a 5.1Mb region (24.2 Mb to 29.3 Mb; CanFam2.0) on chromosome CFA14.

Molecular basis: Among the 21 positional candidate genes in the region to which this disorder was mapped (see Mapping section), Wolf et al. (2014) identified two (DLX5 and DLX6) as functional candidates (being transcription factors involved in craniofacial development; and containing causal mutations in mice). Sanger sequencing of the coding regions and conserved introns of these two genes in 1 affected and 1 unaffected Nova Scotia Duck Tolling Retriever revealed a "2056 bp [LINE-1] insertion . . . within a highly conserved region of DLX6 intron 2 at cfa14.25016716" as the most likely causal mutation. As reported by the same authors, "The LINE-1 insertion is predicted to insert a premature stop codon within the homeodomain of DLX6." Genotyping for this mutation in a range of families in which the disorder is segregating confirmed it as causal.

Clinical features: As reported by Wolf et al. (2014), this syndrome is best summarised as "relative mandibular brachygnathia and cleft palate". As detailed by the same authors, in the syndrome specified as CP1 "clefts were characterized by abnormal or missing palatine fissures, missing or small palatine processes of the maxilla, and small, missing, or abnormally shaped palatine bones . . . The nasal septum was absent or poorly developed. . . .variation from the normal angulation of the condylar process [of mandibles] was observed". These same authors also reported that "CP1 NSDTRs [Nova Scotia Duck Tolling Retrievers] had relatively shorter mandibles by an average of 5.46 mm when compared to the normal NSDTRs".

Prevalence: As reported by Wolf et al. (2014), "Within the NSDTR breed, 96 dogs were genotyped and 80 NSDTRs did not carry the insertion, while the remaining 16 NSDTRs were heterozygous for the insertion. To determine if the insertion was shared among other breeds, 35 affected dogs from 20 other breeds and 284 unaffected dogs from 69 breeds were genotyped. No carriers were identified. This is consistent with a fully penetrant autosomal recessive causative mutation that is private to the NSDTR breed."

Breed: Nova Scotia Duck Tolling retriever.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
DLX6 distal-less homeobox 6 Canis lupus familiaris 14 NC_006596.3 (22067253..22086284) DLX6 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Nova Scotia Duck Tolling retriever Cleft palate 1 DLX6 insertion, gross (>20) CanFam2.0 14 "2056 bp [LINE-1] insertion . . . within a highly conserved region of DLX6 intron 2 at cfa14.25016716 2014 24699068

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2017 Peralta, S., Fiani, N., Kan-Rohrer, K.H., Verstraete, F.J.M. :
Morphological evaluation of clefts of the lip, palate, or both in dogs. Am J Vet Res 78:926-933, 2017. Pubmed reference: 28738009. DOI: 10.2460/ajvr.78.8.926.
2014 Wolf, Z.T., Leslie, E.J., Arzi, B., Jayashankar, K., Karmi, N., Jia, Z., Rowland, D.J., Young, A., Safra, N., Sliskovic, S., Murray, J.C., Wade, C.M., Bannasch, D.L. :
A LINE-1 Insertion in DLX6 Is Responsible for Cleft Palate and Mandibular Abnormalities in a Canine Model of Pierre Robin Sequence. PLoS Genet 10:e1004257, 2014. Pubmed reference: 24699068. DOI: 10.1371/journal.pgen.1004257.

Edit History


  • Created by Frank Nicholas on 09 Apr 2014
  • Changed by Frank Nicholas on 09 Apr 2014