ICCFGG 2022
#19 Canine disorder of sex development — pathological and genomic analyses of an asymmetric hermaphroditism case in a female Labrador Retriever Haolong Wang1 , Kellye Joiner1, Wenqi Cao1, Xiao Xiong1, Lisa Parsons1, Cailtlyn Scagliarini1, Aime Johnson2, Robyn R. Wilborn2, Jamie Bellah2, and Xu Wang1,3,4,5 hzw0088@auburn.edu 1Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA, 2Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL, USA, 3Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL, USA, 4Alabama Agricultural Experiment Station, Auburn, AL, USA, 5HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA In phenotypic sex development disorders, the gonad sex agrees with sex chromosome config- uration, but external genitalia have characteristics of the opposite sex. To date, ~25 such cases have been reported, none of which are labrador retrievers. In this study, we reported a case of a hermaphrodite labrador retriever identified at 6 weeks of age in 2006. Karyotyping confirmed 78, XX (Sry-), a normal female without any apparent chromosomal abnormalities. Physical examina- tion of the puppy found an imperforate anus (Type 2 Atresia ani, 7 in 100,000 dogs), male/female external genitalia, and perianal asymmetry. The female side of the reproductive system consists of 2 normal ovaries, separate uterine horns, and cervis connected to the vagina. The male side includes a rudimentary scrotum, penis, and prepuce. The urinary system is also asymmetric with sagittal duplication of bladders: right ectopic ureter on the male side, and the right and left urinary bladders separated by a fibromuscular septum. As an adult, the dog continued to urinate from both the penis and the vulva. To identify the genetic basis of this unique hermaphroditism, we performed whole-genome resequencing in male-specific, female-specific, and somatic tissues. De novo SNP calling identified 1.7 million candidate SNPs compared to canFam3.1, of which only 0.15% differ between male and female/somatic tissues. Subsequent analysis revealed almost all SNPs are unlikely to be causal, which are also segregating in normal dogs. Functional consequence analysis did not find any damaging alleles, and targeted analysis of sex-reversal genes did not identify any candidate either. Our results indicate this unique asymmetric hermaphroditism is not genetic, presumably due to errors in early gonad developmental reprogramming.
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