A Lack of Association between Polymorphisms of Three Positional Candidate Genes <b><i>(CLASP2</i></b>, <b><i>UBP1,</i></b> and <b><i>FBXL2)</i></b> and Canine Disorder of Sexual Development (78,XX; <b><i>SRY</i></b>-Negative)

Abstract

A disorder of sexual development (DSD) of dogs with a female karyotype, missing SRY gene, and presence of testicles or ovotestes is quite commonly diagnosed. It is suggested that this disorder is caused by an autosomal recessive mutation; however, other models of inheritance have not been definitely ruled out. In an earlier study it was hypothesized that the mutation may reside in a pericentromeric region of canine chromosome 23 (CFA23). Three positional candidate genes (CLASP2, UBP1, and FBXL2) were selected in silico in the search for polymorphisms in 7 testicular or ovotesticular XX DSD dogs, 8 XX DSD dogs of unknown cause (SRY-negative, with enlarged clitoris and unknown histology of gonads), and 29 normal female dogs as a control group. Among the 15 molecularly studied dogs with enlarged clitoris there were 3 new cases of testicular or ovotesticular XX DSD and 4 new cases of XX DSD with unknown cause (histology of the gonads unknown). Altogether, 11 (including 10 novel) polymorphisms in 5′- and 3′-flanking regions of the studied genes were found. The distribution analysis of these polymorphisms showed no association with the DSD phenotypes. Thus, it was concluded that the presence of the causative mutation for testicular or ovotesticular XX DSD in the pericentromeric region of CFA23 is unlikely.

A Rare Case of Testicular Disorder of Sex Development in a Dog (78,XX; <b><i>SRY</i></b>-Negative) with Male External Genitalia and Detection of Copy Number Variation in the Region Upstream of the <b><i>SOX9</i></b> Gene

“…4 ). To date XX ( SRY -negative) DSD in French Bulldogs has been described in 3 reports [Campos et al, 2011;Silversides et al, 2011, Salamon et al, 2014. In all these cases an enlarged clitoris and inactive testes were observed.…”

Copy number variation in the region harboring SOX9 gene in dogs with testicular/ovotesticular disorder of sex development (78,XX; SRY-negative)

“…There have been numerous attempts to identify the causative mutation or linked genetic markers in dogs, but so far without success [reviewed by 1 16 17 ]. It has recently been claimed that some canine XX DSD cases are caused by duplication of a 577 kb region containing the SOX9 gene, as detected by array comparative genome hybridization (aCGH) and confirmed by real time qPCR.…”

Identification of ectopic ovotestis in a dog with XX ovotesticular, SRY‐negative, disorder of sexual development

“…XX ovotesticular DSD has been described in more than 30 canine breeds such as Basset Hound, Beagle, Collie, Poodles, Pug, Soft-Coated Wheaten Terriers etc. (Meyers-Wallen, 2012;Poth et al, 2010;Salamon et al, 2014).…”