Presenter Ellen Schofield
Authors Ellen Schofield (1), Louise Pettitt (1), [Wisdom/Blue Pearl], Cathryn Mellersh (1), Oliver Forman (2)
Affiliations 1. The Canine Genetics Centre, University of Cambridge, Cambridge, United Kingdom. 2. Wisdom Panel, Mars Petcare Science and Diagnostics, Leicestershire, United Kingdom
Presentation Type Poster
Abstract
Osteogenesis imperfecta (OI), or brittle bone disease, is a genetic disorder characterised by fragile bones and loose joints due to poor collagen formation, leading to spontaneous fractures and other health issues. In humans, mutations in genes involved in the collagen synthesis pathway have been shown to cause OI and there are currently 19 recognised types. OI has been shown to have autosomal recessive, dominant and X-linked patterns of inheritance in both human and dogs.
A single adult male Miniature Schnauzer (MS) presented with clinical signs consistent with osteogenesis imperfecta (OI) to a veterinary referral centre. Other potential known genetic causes were excluded so whole genome sequencing (WGS) was undertaken by Wisdom and the data sent over to the Canine Genetics Centre (CGC) for further analysis. Due to limited case history, all possible inheritance patterns were hypothesised.
The data from the individual case were incorporated into a cross-breed joint-called dataset of 53 Kennel Club (KC) toy group breeds, including 15 additional MS. Following filtering and segregation, including comparisons with the Dog10K dataset of ~1900 samples, eight variants remained that were consistent with an autosomal-recessive mode of inheritance.
All eight identified variants are located in genes not directly implicated in the collagen synthesis pathway; however, one gene, SPARC, has previously been associated with recessive forms of human osteogenesis imperfecta (OI). The predicted high-impact single-base insertion within exon 7 of SPARC introduces a frameshift, resulting in a premature termination codon and consequent truncation of the mature protein.
A novel single nucleotide variant (SNV) associated with canine OI was identified. Further screening of MS is being undertaken to investigate the variant prevalence in the wider population.