Heritability and complex segregation analysis of hypoadrenocorticism in the standard poodle

Abstract

The heritability of hypoadrenocorticism (Addison's disease) was evaluated in 778 standard poodles with known Addisonian phenotypes. Addisonian status was confirmed clinically by adrenocorticotropic hormone (ACTH) challenge and 8.6 per cent of the poodles enrolled in the study were classified as being Addisonian. Hypoadrenocorticism affected both sexes with equal probability (P > 0.1). The most common coat colours had a negligible effect on the incidence of hypoadrenocorticism (P > 0.09), although red coat colour had a significant impact on the disease, probably due to the relatively small numbers of dogs with that coat colour. The heritability of hypoadrenocorticism in the standard poodle was estimated to be 0.75. Complex segregation analyses suggested that hypoadrenocorticism in the breed is influenced by an autosomal recessive locus. Clarification of both the heritability and mode of inheritance of hypoadrenocorticism in the standard poodle allows for better-informed breeding decisions.

Evaluation of the genetic basis of primary hypoadrenocorticism in Standard Poodles using SNP array genotyping and whole-genome sequencing

“…Pedigree studies have estimated a relatively high heritability in these breeds, ranging from 0.49 in PWDs to 0.98 in NSDTRs (Famula et al 2003; Oberbauer et al 2006; Hughes et al 2007). Attempts to identify specific polymorphisms in dogs with AD have recently been reviewed (Boag and Catchpole 2014).…”

“…We focused on Standard Poodles because this breed has a relatively high incidence of the disease at ~8–10%, a high estimated heritability of 0.76, and a possible major causative locus with an autosomal recessive inheritance pattern (Famula et al 2003). Based upon this information, while accounting for studies in humans suggesting a complex inheritance pattern, we hypothesized that a combination of a genome-wide association study (GWAS) and whole-genome sequencing (WGS) would allow us to identify specific causative variants that lead to the development of AD in Standard Poodles.…”

Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs

“…Further studies that include a larger number of within-breed samples may be helpful in determining whether certain breeds that develop immune-mediated disease have a higher frequency of the DLA-79*001:02 allele. Nevertheless, canine immune-mediated diseases tend to cluster strongly within breeds and because non-genetic effects (e.g., environmental exposures, viruses) are likely to play a key role in the onset of these diseases, completely controlling for breed may be disadvantageous as it limits insights into disease-causing mutations that may be fixed within breeds (Famula et al 2003; Salzmann et al 2011; Piek 2011; Bogdanos et al 2012; Costenbader et al 2012; Selmi et al 2012; Catchpole et al 2013). Additionally, because of these non-genetic influences on phenotype, truly describing an animal as “unaffected” is challenging as an animal that never develops clinical disease may in fact have a predisposing genetic variant but never have come in contact with a required environmental exposure.…”

“…Many immune-mediated diseases in dogs have strong breed associations and are believed to be inherited (Famula et al 2003; Chase et al 2006; Wilbe et al 2010a; Wilbe et al 2010c; Salzmann et al 2011; Wang et al 2011; Pedersen et al 2012a; Massey et al 2014). One approach to decreasing the frequency of these diseases involves breeding programs that consider the role of predisposing genetic polymorphisms.…”

Putative candidate genes for canine hypoadrenocorticism (Addison's disease) in multiple dog breeds

“…There is, however, a reported genetic basis in a number of breeds (Shaker and others 1988, Burton and others 1997, Oberbauer and others 2002, 2006, Famula and others 2003, Chase and others 2006, Hughes and others 2007, 2009, Short and others 2013) with anecdotal reports in others (West Highland white terrier, great dane and soft coated wheaten terrier). We extended the candidate gene analyses of canine hypoadrenocorticism (Short and others 2013) to seven additional breeds: bearded collie (24 affected, 38 control), border collie (12 affected, 18 control), German shepherd dog (11 affected, 14 control), standard poodle (10 affected, 11 control), Jack Russell terrier (13 affected, 24 control), West Highland white terrier (32 affected, 90 control) and soft coated wheaten terrier (12 affected, 20 control) to further resolve the genetic heterogeneity of the condition in dogs.…”