Two recessive mutations in FGF5 are associated with the long-hair phenotype in donkeys.
BACKGROUND
Seven donkey breeds are recognized by the French studbook. Individuals from the Pyrenean, Provence, Berry Black, Normand, Cotentin and Bourbonnais breeds are characterized by a short coat, while those from the Poitou breed (Baudet du Poitou) are characterized by a long-hair phenotype. We hypothesized that loss-of-function mutations in the FGF5 (fibroblast growth factor 5) gene, which are associated with a long-hair phenotype in several mammalian species, may account for the special coat feature of Poitou donkeys. To the best of our knowledge, mutations in FGF5 have never been described in Equidae.


METHODS
We sequenced the FGF5 gene from 35 long-haired Poitou donkeys, as well as from a panel of 67 short-haired donkeys from the six other French breeds and 131 short-haired ponies and horses.


RESULTS
We identified a recessive c.433_434delAT frameshift deletion in FGF5, present in Poitou and three other donkey breeds and a recessive nonsense c.245G > A substitution, present in Poitou and four other donkey breeds. The frameshift deletion was associated with the long-hair phenotype in Poitou donkeys when present in two copies (n = 31) or combined with the nonsense mutation (n = 4). The frameshift deletion led to a stop codon at position 159 whereas the nonsense mutation led to a stop codon at position 82 in the FGF5 protein. In silico, the two truncated FGF5 proteins were predicted to lack the critical β strands involved in the interaction between FGF5 and its receptor, a mandatory step to inhibit hair growth.


CONCLUSIONS
Our results highlight the allelic heterogeneity of the long-hair phenotype in donkeys and enlarge the panel of recessive FGF5 loss-of-function alleles described in mammals. Thanks to the DNA test developed in this study, breeders of non-Poitou breeds will have the opportunity to identify long-hair carriers in their breeding stocks.
UMR955 INRA-ENVA de Génétique Fonctionnelle et Médicale, Université Paris-Est, Institut National de la Recherche Agronomique, Ecole nationale vétérinaire d'Alfort, F-94700, Maisons-Alfort, France. romainlegrand.vet@gmail.com.
Romain
R
Legrand
UMR955 INRA-ENVA de Génétique Fonctionnelle et Médicale, Université Paris-Est, Institut National de la Recherche Agronomique, Ecole nationale vétérinaire d'Alfort, F-94700, Maisons-Alfort, France. ltiret@vet-alfort.fr.
Laurent
L
Tiret
UMR955 INRA-ENVA de Génétique Fonctionnelle et Médicale, Université Paris-Est, Institut National de la Recherche Agronomique, Ecole nationale vétérinaire d'Alfort, F-94700, Maisons-Alfort, France. m.abitbol@vet-alfort.fr.
Marie
M
Abitbol
D000483:Alleles; D000818:Animals; D018397:Equidae / Q000235:genetics*; D051521:Fibroblast Growth Factor 5 / Q000235:genetics*; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006197:Hair / Q000502:physiology*; D006736:Horses / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic
D051521:Fibroblast Growth Factor 5