Osteogenesis imperfecta in the dachshund

Osteogenesis imperfecta in the dachshund Osteogenesis imperfecta (OI) in the Dachshund is due to a recessive mutation in the SERPINH1 gene (serpin H1, serinarginine-protease inhibitor, heat shock protein 47, collagen-binding protein 1). An alteration or loss of function of SERPINH1 results in a misfolding of collagen fibrils and consequently to an abnormal ossification. Homozygous mutant animals are nonviable and usually die shortly after birth with multiple bone fractures often already acquired during foetal development. In the present study, we analysed 591 Dachshunds for the presence of the SERPINH1 mutation and recorded the rate of stillborn puppies. The association between both parameters was recorded in male dogs with at least 15 registered litters. The allele frequency of the SERPINH1 mutation was calculated to be 8.86%. In litters of heterozygous male Dachshunds, the mortality rate was exceedingly significantly higher (p = 0.00002; n = 3299 puppies) than in dogs without this mutation (odds-ratio: 1.8). One affected homozygous Dachshund showed the typical clinic signs of OI with brittle bones, fractures, and translucent reddish teeth. In summary, we were able show that the causative OI mutation within the SERPINH1 gene in the Dachshund results in a significantly increased mortality rate among the offspring of carriers. Due to the relatively high allele frequency of the mutated allele and animal welfare issues involved, dogs that are used for breeding should be tested using the robust DNA-based assay described here. With a consistent implementation of DNA-based diagnosis, it should be possible to eliminate carriers gradually with preservation of the genetic diversity in the breeding population.