Abstract
BackgroundCanine atopic dermatitis (AD) is a common, heritable, chronic allergic skin condition prevalent in the West Highland White Terrier (WHWT). In canine AD, environmental allergens trigger an inflammatory response causing visible skin lesions and chronic pruritus that can lead to secondary bacterial and yeast infections. The disorder shares many of the clinical and histopathological characteristics of human AD and represents an animal model of this disorder that could be used to further elucidate genetic causes of human AD. Microsatellite markers genotyped in families of WHWTs affected with AD were used to perform a genome-wide linkage study in order to isolate chromosomal regions associated with the disorder.ResultsBlood samples and health questionnaires were collected from 108 WHWTs spanning three families. A linkage simulation using these 108 dogs showed high power to detect a highly penetrant mutation. Ninety WHWTs were genotyped using markers from the Minimal Screening Set 2 (MSS-2). Two hundred and fifty six markers were informative and were used for linkage analysis. Using a LOD score of 2.7 as a significance threshold, no chromosomal regions were identified with significant linkage to AD. LOD scores greater than 1.0 were located in a 56 cM region of chromosome 7.ConclusionsThe study was unable to detect any chromosomal regions significantly linked to canine AD. This could be a result of factors such as environmental modification of phenotype, incorrect assignment of phenotype, a mutation of low penetrance, or incomplete genome coverage. A genome-wide SNP association study in a larger cohort of WHWTs may prove more successful by providing higher density coverage and higher statistical power.
Highlights
Canine atopic dermatitis (AD) is a common, heritable, chronic allergic skin condition prevalent in the West Highland White Terrier (WHWT)
In canine AD, environmental allergens such as house dust mites [6] trigger an inflammatory response leading to the development of erythematous macules and papular lesions [7]
Clinical signs usually manifest between six months and three years of age and the chronic pruritus associated with AD leads to excessive licking, alopecia, hyperpigmentation, scaling, lichenification and secondary
Summary
Canine atopic dermatitis (AD) is a common, heritable, chronic allergic skin condition prevalent in the West Highland White Terrier (WHWT). In canine AD, environmental allergens trigger an inflammatory response causing visible skin lesions and chronic pruritus that can lead to secondary bacterial and yeast infections. Canine AD shares many of the clinical and histopathological characteristics of human AD and is a good animal model for the disease [10] that could prove useful in uncovering additional causative genes in humans. Investigation of the orthologous canine gene for FLG, located on canine chromosome 17 (CFA 17), in a cohort of WHWTs failed to show linkage to canine AD [16] raising the possibility that investigation of the cause of AD in dogs may uncover new candidate genes for the human condition. The study was unable to detect any chromosomal regions significantly linked to canine AD in WHWTs using a genome-wide family-based linkage approach
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