title: Genetics of canine anal furunculosis in the German shepherd dog.
abstract: Canine anal furunculosis (AF) is characterised by ulceration and fistulation of perianal tissue and is a disease that particularly affects German shepherd dogs (GSDs). There are some similarities between AF and perianal Crohn's disease (CD) in man. An immune-mediated aetiopathogenesis for AF has been suggested due to tissue pathology, a major histocompatibility complex (MHC) association and clinical response to ciclosporin. Genome-wide association studies (GWAS) can be conducted in dogs with fewer markers and individuals than would be required in a human study. A discovery GWAS was performed on 21 affected and 25 control GSDs from the UK. No SNPs reached genome-wide significance levels at this stage. However, 127 nominally associated SNPs were genotyped in further 76 cases and 191 controls from the UK and Finland. Sequencing of these regions was undertaken to discover novel genetic variation. Association testing of these variants in the UK and Finnish cohorts revealed nine significantly associated SNPs, six of which cause non-synonymous changes in protein sequence. The ADAMTS16 and CTNND2 gene regions were most significantly associated with disease. Members of the butyrophilin protein family, important in intestinal inflammatory regulation, were also associated with disease, but their independence from the MHC region remains to be established. The CTNND2 gene region is also interesting as this locus was implicated in human ulcerative colitis and CD, albeit at a different candidate gene: DAP. We suggest that this represents a common association between inflammatory bowel disease-related conditions in both species and believe that future studies will strengthen this link.
authors.affiliation: Centre for Integrated Genomic Medical Research (CIGMR), Institute of Population Health, Faculty of Medical and Human Sciences, University of Manchester, 2.722 Stopford Building, Oxford Road, Manchester, M13 9PT, UK, jonathan.massey@manchester.ac.uk.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Massey
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Short
authors.forename: Brian
authors.initials: B
authors.lastname: Catchpole
authors.forename: Arthur
authors.initials: A
authors.lastname: House
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Day
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
authors.forename: William E R
authors.initials: WE
authors.lastname: Ollier
authors.forename: Lorna J
authors.initials: LJ
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D001004:Anus Diseases / Q000662:veterinary*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005387:Finland; D005667:Furunculosis / Q000662:veterinary*; D055106:Genome-Wide Association Study; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D006113:United Kingdom