title: A single-base change in the tyrosine kinase II domain of ovine FGFR3 causes hereditary chondrodysplasia in sheep.
abstract: Ovine hereditary chondrodysplasia, or spider lamb syndrome (SLS), is a genetic disorder that is characterized by severe skeletal abnormalities and has resulted in substantial economic losses for sheep producers. Here we demonstrate that a non-synonymous T>A transversion in the highly conserved tyrosine kinase II domain of a positional candidate gene, fibroblast growth factor receptor 3 (FGFR3), is responsible for SLS. We also demonstrate that the mutant FGFR3 allele has an additive effect on long-bone length, calling into question the long-standing belief that SLS is inherited as a strict monogenic, Mendelian recessive trait. Instead, we suggest that SLS manifestation is determined primarily by the presence of the mutant FGFR3 allele, but it is also influenced by an animal's genetic background. In contrast to FGFR3 mutations causing dwarfism in humans, this single-base change is the only known natural mutation of FGFR3 that results in a skeletal overgrowth phenotype in any species.
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana, IL 61801-4734, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Beever
authors.forename: M A
authors.initials: MA
authors.lastname: Smit
authors.forename: S N
authors.initials: SN
authors.lastname: Meyers
authors.forename: T S
authors.initials: TS
authors.lastname: Hadfield
authors.forename: C
authors.initials: C
authors.lastname: Bottema
authors.forename: J
authors.initials: J
authors.lastname: Albretsen
authors.forename: N E
authors.initials: NE
authors.lastname: Cockett
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005097:Exostoses, Multiple Hereditary / Q000235:genetics / Q000662:veterinary*; D005121:Extremities / Q000473:pathology; D040461:Gene Components; D040582:Inheritance Patterns / Q000235:genetics; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA / Q000662:veterinary; D012756:Sheep; D012757:Sheep Diseases / Q000235:genetics*
chemical_list: D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3