Searching for "monogenic diabetes" in dogs using a candidate gene approach
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RESEARCH
Open Access
Searching for “monogenic diabetes” in dogs using a candidate gene approach Andrea D Short1*, Angela Holder2, Simon Rothwell1, Jonathan Massey1, Rachel Scholey1, Lorna J Kennedy1, Brian Catchpole2 and William ER Ollier1
Abstract Background: Canine diabetes is a common endocrine disorder with an estimated breed-related prevalence ranging from 0.005% to 1.5% in pet dogs. Increased prevalence in some breeds suggests that diabetes in dogs is influenced by genetic factors and similarities between canine and human diabetes phenotypes suggest that the same genes might be associated with disease susceptibility in both species. Between 1-5% of human diabetes cases result from mutations in a single gene, including maturity onset diabetes of the adult (MODY) and neonatal diabetes mellitus (NDM). It is not clear whether monogenic forms of diabetes exist within some dog breeds. Identification of forms of canine monogenic diabetes could help to resolve the heterogeneity of the condition and lead to development of breed-specific genetic tests for diabetes susceptibility. Results: Seventeen dog breeds were screened for single nucleotide polymorphisms (SNPs) in eighteen genes that have been associated with human MODY/NDM. Six SNP associations were found from five genes, with one gene (ZFP57) being associated in two different breeds. Conclusions: Some of the genes that have been associated with susceptibility to MODY and NDM in humans appear to also be associated with canine diabetes, although the limited number of associations identified in this study indicates canine diabetes is a heterogeneous condition and is most likely to be a polygenic trait in most dog breeds. Keywords: Diabetes mellitus, Dog breeds, Candidate genes
Lay summary Diabetes is a common condition where sugar (glucose) levels of the body are poorly regulated, due to either lack of production of the hormone insulin, made in the pancreas, or an increase in resistance of tissues in the body to the effects of insulin. Canine diabetes is similar to some forms of human diabetes; it is relatively common in dogs, and its prevalence (the proportion of dogs affected at a point in time) ranges from 0.005% to 1.5%, and is dependent on which breed is being considered. This breed-related variation in the prevalence of diabetes suggests a genetic basis in dogs. In humans, some forms of diabetes are due to mutations in just a single gene (these are called monogenic conditions). This study examined 18 genes that are known to be * Correspondence: [email protected] 1 Centre for Integrated Genomic Medical Research, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK Full list of author information is available at the end of the article
associated with human monogenic diabetes, and tested whether they are also associated with diabetes in 17 different dog breeds. Six variants from five genes were found to be associated with diabetes in some breeds. Interestingly, two different variants in the same gene (called ZFP57 - Zi
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