The genomics revolution: will canine atopic dermatitis be predictable and preventable?

Abstract

Background: Heritability studies suggest that atopic dermatitis (AD) involves multiple genes and interactions with environmental factors. Advances in genomics have given us powerful techniques to study the genetics of AD.

Objective: To review the application of these techniques to canine AD.

Results: Candidate genes can be studied using quantitative PCR and genomic techniques, but these are hypothesis-dependent techniques and may miss novel genes. Hypothesis-free techniques avoid this limitation. Microarrays quantify expression of large numbers of genes, although false-positive associations are common. In the future, expression profiling could be used to produce a complete tissue transcriptome. Genome-wide linkage studies can detect AD-associated loci if enough affected dogs and unaffected relatives are recruited. Genome-wide association studies can be used to discover AD-associated single nucleotide polymorphisms without relying on related dogs. Genomic studies in dogs have implicated numerous genes in the pathogenesis of AD, including those involved in innate and adaptive immunity, inflammation, cell cycle, apoptosis, skin barrier formation and transcription regulation. These findings, however, have been inconsistent, and problems include low case numbers, inappropriate controls, inconsistent diagnosis, incomplete genome coverage, low-penetrance mutations and environmental factors.

Conclusions: Canine AD has a complex genotype that varies between breeds and gene pools. Breeding programmes to eliminate AD are therefore unlikely to succeed, but this complexity could explain variations in clinical phenotype and response to treatment. Genotyping of affected dogs will identify novel target molecules and enable better targeting of treatment and management options. However, we must avoid misuse of genomic data.