A clue to the etiology of disorders of sex development from identity-by-descent analysis in dogs with cryptic relatedness.

Disorders of sex development (DSDs) are discrepancies between sex chromosomes and phenotypical sex. Quite common forms of DSD in canine populations include testicular and ovotesticular XX DSDs with a normal set of sex chromosomes. The objective of this study was to identify genes and putative harmful variants for canine XX DSDs. I have reanalyzed data from the whole-genome sequencing of 11 XX DSD French Bulldogs and six XX DSD American Staffordshire Terriers. Identity-by-descent analysis revealed cryptic relatedness in affected French Bulldogs. Causative genes were sought in chromosomal segments shared identical-by-descent by close relatives. In French Bulldogs, the reanalysis identified 19 regions of importance with a total length of just 65.9 Mb. Variant filtering within the regions implicated AKAP2, PIWIL1, POLR3A and SH2D4B as genes that may be involved in individual cases of testicular and ovotesticular XX DSD in French Bulldogs and American Staffordshire Terriers.

Canine copper-associated hepatitis: A retrospective study of 17 clinical cases.

Background: Copper-associated hepatitis (CAH) is a well-documented chronic hepatic disease in dogs. In some breeds, the disease results from an inherited defect in copper metabolism. In others, it is unclear whether its acummulation is a primary or secondary condition. Reports of copper accumulation in dog breeds that are not genetically predisposed are increasing. Aim: To describe the epidemiology, clinical and laboratory findings, liver biopsy techniques, and treatment response in dogs with CAH. Methods: A retrospective study was performed, drawing upon medical records from CAH dogs at a Veterinary Referral Hospital in Paris, France. The diagnosis of CAH had been confirmed in these patients by positive rhodanine staining of hepatic tissue obtained through biopsy. Medical records were mined for the following data: age at presentation, sex, breed, chief presenting complaints, abdominal ultrasound (US) findings, and rhodanine staining pattern. Results: A total of 17 dogs were included in the study. Median age at presentation was 8-year old (4-11). No sex predisposition was found. Terriers (4/17) and German Shepherd Dogs (GSD, 3/17) were overrepresented. American Staffordshire Terriers and Beauceron had not previously appeared in case reports on CAH; two of each breed were identified in this study. Clinical signs of affected dogs were non-specific. An incidental identification of increased liver-enzymes was observed in 5/17 dogs. A heterogeneous, mottled liver was frequently described (5/17) on abdominal US. Liver biopsies were performed by US-guided percutaneous approach in 10/17 dogs, laparoscopy and laparotomy in 6/17 and 1/17, respectively. The rhodanine staining pattern was centrilobular (zone 3) in 8/17 dogs and periportal (zone 1) in 3/17 dogs. The pattern was considered multifocal in 6/17 dogs. Conclusion: Increased liver enzymes may be the only clinical finding in dogs with copper-associated hepatitis, reflecting the silent progression of this disease. Centrilobular pattern of rhodanine staining was observed in the majority of cases suggesting the primary condition of the disease. Results of this study are consistent with the current literature, which reports that terriers and GSD are predisposed to CAH. This is the first description of CAH in Beauceron and American Staffordshire Terrier dogs.