In other species: chimpanzee , domestic cat , horse

Categories: Integument (skin) phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 603165 (trait) , 605803 (trait) , 605804 (trait) , 605805 (trait) , 605844 (trait) , 605845 (trait) , 613064 (trait) , 613518 (trait) , 613519 (trait)

Mendelian trait/disorder: unknown

Disease-related: yes

Species-specific name: Canine atopic dermatitis (CAD)

Inheritance: Shaw et al. (2004) estimated the heritability of CAD (as a binary trait) to be 0.47 in Golden and Labrador Retrievers.

Mapping: The first GWAS to be conducted on this disorder was by Wood et al. (2009), who genotyped each of 25 affected and 23 control Labrador Retrievers with the Illumina Canine SNP20 chip (yielding 22,133 SNPs for analysis). Validation across 8 breeds confirmed the GWAS results which highlighted regions on chromosomes CFA10 and 29, and less-significant regions on a range of other chromosomes. From a linkage analysis of data obtained from a genome scan with 256 microsatellites on 108 West Highland White Terriers, Salzmann et al. (2011) were not able to identify any chromosomal region linked to CAD. A GWAS conducted by Roque et al. (2012) on data from 35 CAD and 25 control West Highland White Terriers, each genotyped with the Affymetrix Canine SNP V2 (yielding around 42,800 SNPs) highlighted a 1.3Mb region on chromosome CFA17. Of the 19 genes in or near this region, one (PTPN22) was of particular interest: "Four haplotypes within this locus were differently distributed between cases and controls in this population of dogs". Tengvall et al. (2013) conducted a GWAS on 91 carefully-defined CAD cases and 88 CAD controls from the Swedish population of German Shepherd dogs, each genotyped with the Illumina 170K CanineHD BeadChip, and allowing for the all-important effect of IgA level. A 1.5Mb region on chromosome CFA27 was highlighted. Subsequent fine-mapping/resequencing reduced this candidate region to a 209kb region containing just one gene, namely the "PKP2 gene, encoding Plakophilin 2 expressed in the desmosomes and important for skin structure".

Clinical features: Clinical and other issues relating to this disorder were comprehensively covered in an extensive series of papers published in Veterinary Immunology and Immunopathology in 2001 (all included in the references below) by the ACVD task force on canine atopic dermatitis.

Prevalence: From an anlysis of "Case records (n = 23,000) from [the] University [of Sydney] Veterinary Teaching Hospital (UVTH) dogs, including 722 with CAD" compared with 13 previous studies, Mazrier et al. (2016) reported that "Eleven dog breeds with significant increased OR (≥1.0) were identified; all with breed CAD cases proportionally higher than their base hospital population. Gender risk in males from the pug dog breed (P = 0.007) was detected and the bichon frise breed had a similar trend (P = 0.05). Sixteen predisposed dog breeds were identified by systematic review. All breeds with significant increased OR in UVTH had ADRPR > 1.4; five (boxer, bulldog, Labrador retriever, pug, West Highland white terrier) were recognized as predisposed worldwide. One clade of breeds with common ancestry was highly represented in CAD cases worldwide and in Australia (81% of the significant OR cases)."

Breeds: Boxer (Dog) (VBO_0200210), Bulldog (Dog) (VBO_0200258), German Shepherd Dog (Dog) (VBO_0200577), Labrador Retriever (Dog) (VBO_0200800), Pug (Dog) (VBO_0201089), West Highland White Terrier (Dog) (VBO_0201415).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).