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Duplication of FGF3, FGF4, FGF19 and ORAOV1 causes hair ridge and predisposition to dermoid sinus in Ridgeback dogs


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.

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Figure 1: Phenotypes of Rhodesian and Thai Ridgeback dogs.
Figure 2: Duplication in Ridgeback dogs.


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We thank C. Knudsen for access to dorsal skin samples from Rhodesian Ridgebacks, L. Gaffney for help with illustrations, D. Wright for statistical analysis, L. Spångberg for technical assistance and the Broad Institute of MIT and Harvard Genetic analysis Platform for SNP array genotyping. The work was supported by the Foundation for Strategic Research, the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, the Swedish Research Council, the Swedish Kennel Club, the Thure F and Karin Forsbergs Foundation, the American Kennel Club/Canine Health Foundation (grant 373) and EU FP6 IP MolTools.

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N.H.C.S.H. was responsible for collection of field material, histopathological confirmation of dermoid sinus and autopsies together with E.H., phenotypic characterization of the field material, break-point analyses together with M.I., and real-time PCR analyses; M.I. and M.N. were responsible for the MLGA analyses; E.K.K. carried out the SNP association and bioinformatics analyses; E.H. carried out the histological analyses; G.R.P. did pyrosequencing, P.S. carried out the sequencing of mitochondrial DNA and performed phylogenetic analyses; C.M.W. contributed to the SNP screen, H.v.E. took part in the collection of tissue samples; U.G. provided technical assistance; Å.H. provided advice for the clinical part of the study; K.L.-T., L.A. and G.A. co-directed the study; and N.H.C.S.H., L.A., G.A., and K.L.-T. were responsible for preparation of the manuscript with input from the other authors.

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Correspondence to Leif Andersson or Göran Andersson.

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Competing interests

A patent application concerning commercial testing for the presence of the Ridge mutation in dogs has been filed. N.H.C.S.-H., G.A., L.A., K.L.-T., M.N. and M.I. are listed as inventors on a provisional application to the US Patent Office (no. 60/928240) related to this work.

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Supplementary Methods, Note, Tables 1–3, Figures 1–3 (PDF 484 kb)

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Salmon Hillbertz, N., Isaksson, M., Karlsson, E. et al. Duplication of FGF3, FGF4, FGF19 and ORAOV1 causes hair ridge and predisposition to dermoid sinus in Ridgeback dogs. Nat Genet 39, 1318–1320 (2007).

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