Scientists in Scandinavia have identified one of the genetic risk factors underlying the immune-mediated disease Symmetrical lupoid onychodystrophy (SLO) that can lead to severe claw problems in dogs. The results, published in the Public Library of Science (PLoS) ONE journal, can help enhance knowledge about similar nail diseases that affect humans. EU support for the research came from the LUPA ('Unravelling the molecular basis of common complex human disorders using the dog as a model system') project, which received EUR 12 million under the Health Theme of the Seventh Framework Programme (FP7). The researchers at the Swedish University of Agricultural Sciences (SLU), Norwegian School of Veterinary Science (NVH), and Uppsala University (UU) in Sweden say the disease causes the body's immune system to react abnormally which leads to the sloughing of claws from claw beds. As the disease progresses, all claws become affected and this ultimately leads to the destruction of the underlying claw tissue and deformation of the claws. The disease is painful and affected dogs suffer greatly. While SLO affects many different dog breeds, this latest study focused on a few breeds that have a high incidence of the disease, namely Gordon Setters, Bearded Collies and Giant Schnauzers, explained PhD student Maria Wilbe from the Department of Animal Breeding and Genetics, Biomedical Centre, SLU, and first author of the report, which was the result of a collaboration between geneticists and veterinarians. The identified genetic risk factors are genes in the major histocompatibility complex (MHC) class II region that encodes proteins that control the immune response. These genes have been shown to be important genetic risk factors for different autoimmune diseases in both dogs and humans. When the immune system is activated, MHC proteins determine the molecules towards which the attack should be directed. In autoimmunity, MHC proteins will erroneously recognise the body's self molecules and trigger the destruction of the body's own tissues and organs. Such disturbances can, in certain cases, result in development of autoimmune diseases such as SLO. 'We have earlier shown that MHC class II is a genetic risk factor for some other autoimmune diseases in dogs,' said Ms Wilbe. 'In the current study, we identify both a protective MHC class II type and another one that leads to increased risk for the claw disorder.' A major increased risk for SLO development was found in Gordon Setter dogs that had inherited the MHC class II risk type from both parents. In dogs that had inherited the two variants from either parents it was found that the effect of the protective type dominated and such dogs were healthy. Concerning how the results can lead to increased knowledge about similar nail diseases that affect humans, the researchers pointed out that dogs and humans share a similar set of orthologous genes, live in the same environment and are affected by diseases of similar aetiology. Therefore, 'the dog is an excellent model for studies on genetic diseases,' they claimed, noting that 'in humans, several keratin disorders exist with similarities to SLO'. The researchers are currently pursuing additional genetic research and hope to fund continuous research to identify additional genetic risk factors for this claw disease.