Analysis of XX SRY-Negative Sex Reversal Dogs

Abstract

Impaired fertility associated with disorders of sex development (DSDs) due to genetic causes in dogs are more and more frequently reported. Affected dogs are usually of specific breeds thus representing a cause of economic losses for breeders. The aim of this research is to report the clinical, cytogenetic and molecular genetic findings of four XX SRY-negative DSD dog cases. All the subjects showed a female aspect and the presence of an enlarged clitoris with a penis bone. Morphopathological analyses performed in three of the four cases showed the presence of testes in two cases and ovotestis in another. Conventional and R-banded cytogenetic techniques were applied showing that no chromosome abnormalities were involved in these DSDs. CGH arrays show the presence of 11 copy number variations (CNVs), one of which is a duplication of 458 Kb comprising the genomic region between base 17,503,928 and base 17,962,221 of chromosome 9 (CanFam3 genome assembly). This CNV, confirmed also by qPCR, includes the promoter region of SOX9 gene and could explain the observed phenotype.

Clinical Cytogenetics of the Dog: A Review

“…Some DSD dogs may have chromosome abnormalities (sex chromosome DSD), as described above, but the majority of cases have a normal chromosome set described as XX DSD or XY DSD. Sex chromosomes are usually identified in such cases by Giemsa staining, karyotyping of R-banded chromosomes, or FISH with chromosome-specific probes ( Figure 3 ) [ 32 , 59 , 60 , 61 ].…”

“…Since the resolution of the hybridization signals on metaphase chromosomes is not sufficient to detect SOX9 gene triplication, interphase nuclei were examined ( Figure 5 ) [ 64 ]. It should be mentioned that molecular techniques such as MLPA (Multiplex Ligation-dependent Probe Amplification) and a-CGH (array Comparative Genome Hybridization) have also been employed for the identification of this CNV [ 60 , 61 , 62 ].…”

An Unusual Case of Testicular Disorder in Sex Development of Arabian Mare (64,XX SRY-Negative)

“…Moreover, the minimum critical region associated with gonadal development, approximately a 67-kb region located 584-517 kb upstream of SOX9, was confirmed to induce SOX9 overexpression in female-to-male sex reversal [43]. Regulatory elements in the duplication region might enhance SOX9 expression through complex mechanisms [45]. It was suggested that changes in SOX9 expression, resulting from disruptions in some regions upstream of SOX9, could be important in the 46,XX testicular disorder of sexual development.…”

Disorders of sexual development: a case of XX sex reversal in a mixed breed dog negative for SRY (sex-determining region on the Y chromosome) gene

“…Presence of SRY gene results in activation of genes, including SOX9, triggering 'male' development pathway toward formation of testes with internal and external masculinization. 4 Reports of XY sex reversal in dogs are rare. 5,6 Conversely, reports of XX sex reversal in dogs are more common.…”