title: A missense mutation in the SERPINH1 gene in Dachshunds with osteogenesis imperfecta.
abstract: Osteogenesis imperfecta (OI) is a hereditary disease occurring in humans and dogs. It is characterized by extremely fragile bones and teeth. Most human and some canine OI cases are caused by mutations in the COL1A1 and COL1A2 genes encoding the subunits of collagen I. Recently, mutations in the CRTAP and LEPRE1 genes were found to cause some rare forms of human OI. Many OI cases exist where the causative mutation has not yet been found. We investigated Dachshunds with an autosomal recessive form of OI. Genotyping only five affected dogs on the 50 k canine SNP chip allowed us to localize the causative mutation to a 5.82 Mb interval on chromosome 21 by homozygosity mapping. Haplotype analysis of five additional carriers narrowed the interval further down to 4.74 Mb. The SERPINH1 gene is located within this interval and encodes an essential chaperone involved in the correct folding of the collagen triple helix. Therefore, we considered SERPINH1 a positional and functional candidate gene and performed mutation analysis in affected and control Dachshunds. A missense mutation (c.977C>T, p.L326P) located in an evolutionary conserved domain was perfectly associated with the OI phenotype. We thus have identified a candidate causative mutation for OI in Dachshunds and identified a fifth OI gene.
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Berne, Berne, Switzerland.
authors.forename: Cord
authors.initials: C
authors.lastname: Drögemüller
authors.forename: Doreen
authors.initials: D
authors.lastname: Becker
authors.forename: Adrian
authors.initials: A
authors.lastname: Brunner
authors.forename: Bianca
authors.initials: B
authors.lastname: Haase
authors.forename: Patrick
authors.initials: P
authors.lastname: Kircher
authors.forename: Frank
authors.initials: F
authors.lastname: Seeliger
authors.forename: Michael
authors.initials: M
authors.lastname: Fehr
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
authors.forename: Tosso
authors.initials: T
authors.lastname: Leeb
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D050958:HSP47 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D010013:Osteogenesis Imperfecta / Q000235:genetics / Q000662:veterinary*
chemical_list: D050958:HSP47 Heat-Shock Proteins