In other species: domestic cat , taurine cattle

Categories: Integument (skin) phene

Mendelian trait/disorder: yes

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2007

Cross-species summary: Also called dermal sinus tract; neural tube defect (NTD) resulting in failed separation of the neural tube from the skin ectoderm

Species-specific name: ridge; hair ridge; dermoid cyst

Species-specific description: Dermoid sinuses and cysts have been described in dogs from several breeds. Hillbertz and Andersson (2006) reported that in the Rhodesian ridgeback population, dogs with the autosomal dominant ridge are predisposed to dermoid sinuses. Salmon Hillbertz et al. (2007) identified the causative mutation for the autosomal dominant dorsal hair ridge in Rhodesian and Thai Ridgeback dogs and proposed that "the mutation predisposes to dermoid sinus with low penetrance in duplication heterozygotes and with high penetrance in homozygotes."

Inheritance: "[T]he ridge trait [in Rhodesian Ridgeback dogs] is inherited in a dominant fashion; thus a single copy of this duplication results in appearance of a ridge, and dogs with two copies of the duplication are indistinguishable from dogs with one copy" (Waldo and Diaz, 2015) Homozygotes for the Ridge allele are more likely to also have a dermoid sinus (Salmon Hillbertz et al., 2007). Inheritance of dermoid sinuses in other breeds is less well documented.

Mapping: In a landmark study, Karlsson et al. (2007) mapped the hair-ridge locus to a 750kb region on chromosome CFA18 via one of the first Genome-Wide Association Studies (GWAS) using 27,000 SNPs on just "9 ridgeless Rhodesian ridgebacks and 12 ridged controls".

Molecular basis: The 750kb candidate region on CFA18 identified by Karlsson et al. (2007) (see Mapping section) contains five genes, three of which are fibroblast growth factor (FGF) genes that in chickens have an integral role in embryonic development. In an accompanying paper in the same issue of Nature Genetics, Salmon Hillbertz et al. (2007) reported that the hair-ridge phenotype (which predisposes to dermoid sinus) is due to a large duplication encompassing all three FGF genes (FGF3, FGF4, FGF19) and another gene ORAOV1.

Genetic testing: Waldo and Diaz (2015) reported a useful diagnostic test for the duplication causing the ridge allele detailed above. While homozygotes and heterozygotes for the duplication (Ridge allele) have identical ridge appearance (characteristic of ridged breeds), homozygotes for the Ridge allele are more likely to also have a dermoid sinus (Salmon Hillbertz et al., 2007).

Breeds: Chow Chow (Dog) (VBO_0200361), Dachshund (Dog) (VBO_0200406), French Bulldog (Dog) (VBO_0201455), Italian Cane Corso (Dog) (VBO_0200712), Rhodesian Ridgeback (Dog) (VBO_0201135), Siberian Husky (Dog) (VBO_0201233), Thai Ridgeback (Dog) (VBO_0201348), Yorkshire Terrier (Dog) (VBO_0201448).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated genes: