Robertsonian Translocation in a Sex Reversal Dog (XX, <i>SRY </i>negative) May Indicate that the Causative Mutation for This Intersexuality Syndrome Resides on Canine Chromosome 23 (CFA23)

Abstract

A Bernese mountain dog was subjected for clinical evaluation due to the presence of ambiguous external genitalia (enlarged clitoris). Anatomical and histological studies revealed the presence of one testicle, one ovotestis and a uterus. This dog was classified as a female-to-male sex reversal, with 2 normal X chromosomes and a lack of the Y chromosome-linked genes SRY and ZFY. It is the first case of this syndrome in this breed. Apparently a Robertsonian translocation, rob(5;23), was also identified in this dog and it is again the first case of this type of chromosome abnormality in this breed, as well as the first case of co-occurrence of the sex reversal syndrome along with a centric fusion in the dog. Since on the canine chromosome 23 (CFA23) 3 genes (FOXL2,PISRT1 and CTNNB1) involved in the sex determination process are present, further cytogenetic FISH studies were carried out with the use of BAC probes specific for this chromosome. It was found that a pericentromeric fragment of CFA23 was deleted as a result of the centric fusion. We hypothesize that a cis regulatory sequence for the sex determination genes on CFA23 (e.g. proximally located CTNNB1) is present in the deleted fragment. Thus, a causative mutation responsible for this sex reversal syndrome may reside on CFA23.

Hypospadias in a Male (78,XY; <i>SRY</i>-Positive) Dog and Sex Reversal Female (78,XX; <i>SRY</i>-Negative) Dogs: Clinical, Histological and Genetic Studies

“…This intersexuality has been identified to date in more than 20 dog breeds and seems to be a widely distributed DSD in dogs [Meyers-Wallen, 2009;Switonski et al, 2011].…”

“…Genome scanning of a reference family for the sex reversal syndrome indicated that the causative mutation is located on chromosome 29 [Pujar et al, 2007], but recent studies of an intersex carrying a centric fusion chromosome mutation suggested that it may reside on chromosome 23 [Switonski et al, 2011]. Also, several a priori selected candidate genes were analyzed, but no cosegregating mutation was found [see Switonski et al, 2011]. Searching for a mutation predisposing to cryptorchidism was carried out in Siberian husky dogs.…”

Morphological analysis of testicles in cats with disorders of sex development

“…Millis et al (1992) determined the frequency of this disorder at 1.7% in the group of 1345 cats hospitalized in a ten-year period, and Yates et al (2003) reported 1.3% cases of cryptorchidism during a 4.5-year period. While the reversed sex syndrome (78, XX with the occurrence of testis or ovotestis) has been described in many breeds of dogs, such a pathology has not been observed in cats so far (Switonski et al 2011, Christensen 2012. It is suspected that the basis of this anomaly, as in humans or dogs, is a mutation that has not been clearly identified.…”

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)

“…Diagnosis of the DSD animals was performed with cytogenetic (identification of sex chromosomes), molecular (detection of the SRY and ZFY genes), and histological (analysis of gonads) techniques as described earlier by Switonski et al [2011].…”

“…In our earlier study of a DSD dog carrying a Robertsonian translocation, rob (5; 23), we suggested that the causative mutation could reside on chromosome 23 (CFA23), especially in its pericentromeric region [Switonski et al, 2011]. In silico analysis of the CFA23 sequence revealed 3 positional candidate genes in this region : CLASP2 (cytoplasmic linker associated protein 2), UBP1 (upstream binding protein 1), and FBXL2 (F-box and leucine-rich repeat protein 2) .…”