Evaluation of kallikrein 7 (KLK7) and serine protease inhibitor kazal-type 5 precursor (SPINK5) as candidate genes in canine atopic dermatitis in boxer and west highland white terrier

Abstract: Atopic Dermatitis is a genetically predisposed allergic skin disease that affects both humans and dogs. The disease has a complex background influenced by both genetic and environmental factors. The genetic origin is still largely unknown but genetic screens have indicated several different genes or different groups of interacting genes in the aetiology of the disease. These genes are involved, together with environmental factors, in processes that lead to the expression of the clinical phenotype. In humans the genetic background is most likely more complex than in many dog breeds due to the intense inbreeding that many dog populations have experienced. Certain dog breeds are more predisposed to develop Canine Atopic Dermatitis (CAD) than others and high-risk breeds are for instance Boxer and West Highland White Terriers (WHWT). Case and control animals from these two breeds were included in this study where two candidate genes for CAD were evaluated. The genes Kallikrein 7 (KLK7) and Serine Protease Inhibitor Kazal-type 5 precursor (SPINK5) have, based on studies that have implicated these genes in atopic diseases, been selected as candidate genes for CAD. Two different kinds of genetic markers were used in the evaluation; three microsatellites in the near vicinity of the gene were chosen for the evaluation of KLK7, and single-nucleotide polymorphisms (SNPs) were searched for in one intron of SPINK5. No informative SNPs in the SPINK5 gene were found in WHWT (except for individual mutations) but four SNP loci were found within the sequenced area of 1,500 base pairs in Boxer. These SNP alleles were connected into two haplotypes but neither of the haplotypes showed any association with the disease phenotype. However, additional test individuals as well as more polymorphic markers, which are better spread out within and around the gene, are needed for an improved evaluation of SPINK5´s involvement in the disease in these two dog breeds. In KLK7, the three microsatellite-markers were both quite polymorphic (except for one locus in WHWT) and well distributed within and around the gene, and the data conclusively show lack of association between the gene and the disease phenotype.