The dorsal hair ridge in Rhodesian and Thai Ridgeback dogs is caused by a dominant mutation that also predisposes to the congenital developmental disorder dermoid sinus. Here we show that the causative mutation is a 133-kb duplication involving three fibroblast growth factor (FGF) genes. FGFs play a crucial role in development, suggesting that the ridge and dermoid sinus are caused by dysregulation of one or more of the three FGF genes during development.

Dogs with a characteristic dorsal hair ridge seem to have been present in both Africa and Asia long before European colonization (Fig. 1). The Rhodesian Ridgeback dog (Fig. 1a), first registered in South Africa in 1924, is most likely a blend of European dogs (brought to Africa by early colonizers) and an extinct indigenous breed of Africa, the ridged Hottentot Khoi dog1. The Thai Ridgeback (Fig. 1b) and the Vietnamese Phu Quoc dog are two Asian breeds with a dorsal hair ridge closely resembling the one found in Rhodesian Ridgeback dogs.

Histology of the skin from a ridged dog, taken strictly from the dorsal median plane, showed cross-sectioned appendages (that is, hair follicles and sebaceous glands) of normal appearance but lateral orientation (Fig. 1d). In contrast, skin from the median plane of a ridgeless dog showed caudally oriented hair follicles (Fig. 1e). Ridgeback dogs are affected by the congenital malformation dermoid sinus (Fig. 1f), which closely resembles a neural-tube defect in humans that is usually termed dermal sinus (2). In dogs, anatomical locations of dermoid sinus, anterior and posterior to the ridge, correspond with those found in humans. The dermoid sinus was characterized by a tubular indentation of the skin, with keratin and hair in the lumen; appendages such as sebaceous glands and aberrant hair follicles with multiple hair shafts were also observed (Fig. 1g). Dermoid sinus is closely associated with the ridge phenotype, and no ridgeless dogs with dermoid sinus have been reported3. Approximately 5-6% of Rhodesian Ridgebacks born in Sweden are ridgeless, and around 8-10% of ridged offspring have dermoid sinus (3,4). Both ridgeless dogs and dogs with dermoid sinus are excluded from breeding.

We assumed a genetic model in which (i) ridgeless dogs are homozygous (r/r) for the wild-type allele, (ii) ridged dogs without dermoid sinus are heterozygous or homozygous for the Ridge allele (R/r or R/R) and (iii) ridged dogs with dermoid sinus are homozygous R/R. We were able to assign the Ridge locus to a 750-kb region on chromosome 18 using only nine ridgeless and 12 ridged dogs, of which 11 had dermoid sinus, in a genome-wide association analysis5. The results indicated that 10 of 11 dogs with dermoid sinus were homozygous for a haplotype not present among ridgeless dogs. Notably, all Rhodesian ridgebacks with dermoid sinus were heterozygous for a SNP (SNP_51,399,353) within the 750-kb region associated with the phenotype. Further analysis showed that 43 of 45 ridged Rhodesian Ridgebacks were heterozygous for this SNP. This significant deviation (P o 0.001) from Hardy-Weinberg proportions suggested that the SNP is part of...