Trisomy 26 in a Holstein calf with disorders of sex development

Abstract

Hypospadias occurs sporadically in male livestock and is characterized by a non-fused urethra during fetal development. In this study, perineal hypospadias, a bifid scrotum, penile hypoplasia, and bilateral abdominal cryptorchidism were diagnosed in a neonatal Holstein male calf. Septicemia was also suspected due to hypothermia, blurred conjunctivae, and loss of sucking and swallowing reflexes. Gross pathology revealed that both testicles were located intraabdominally caudally to the kidneys. Histopathological examination of the hypospadias showed a urothelium-lined mucosal fold and parts of the corpus cavernosum penis and prepuce in the subcutis. Whole genome sequencing was performed on the affected calf. Analysis of short-read coverage depth along the chromosomes identified an entire extra copy of chromosome 26. Based on the comparison of available variant calling data from the sire, the identified trisomy 26 is due to non-disjunction of homologous chromosomes during the generation of paternal gametes. We have shown for the first time an association between bovine hypospadias and trisomy 26, which adds to the understanding of variation in fetal male sexual development.