Analysis of XX SRY-Negative Sex Reversal Dogs

SIMPLE SUMMARY: The study of XX SRY-negative sex reversal cases is of great interest because testicular tissue develops in these subjects in the absence of SRY gene, thus allowing us to deepen the knowledge of all the other genes involved in the development of testes and the structures related to the male reproductive apparatus. This paper reports the results of the study of four new canine disorders of sex development (DSDs) XX SRY-negative cases in which 11 copy number variations (CNVs) are observed, five of which are never described. 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.