Clinical, cytogenetic and molecular genetic characterization of a tandem fusion translocation in a male Holstein cattle with congenital hypospadias and a ventricular septal defect

Hypospadias, disorder of sex development (DSD), is a sporadic congenital abnormality of the genital region in male ruminants, which is characterized by a non-fused urethra during fetal development. Detailed clinical examination classified the hypospadias phenotype of a male Holstein calf studied here as the perineal type. In combined use of cytogenetic analysis and whole genome sequencing, a non-mosaic, pseudo-monosomy 59, XY + tan(18;27) was detected. This chromosomal aberration had its origin in a tandem fusion translocation of the bovine autosomes (BTA) 18 and 27 with an accompanying loss of genomic sequences mainly in the distal end of BTA 18 and the proximal end of BTA 27. The resulting phenotype included hypospadias, growth retardation and ventricular septal defect.

尿道下裂(Hypospadias)属于性发育异常(DSD)，是雄性反刍动物散发性的生殖系统先天性畸形，以胎儿发育阶段尿道未融合为典型特征。本研究针对一头雄性荷斯坦犊牛开展，经详细临床检查将其尿道下裂表型归类为会阴型。研究联合采用细胞遗传学分析与全基因组测序技术，检出非嵌合型假单倍体核型59,XY + t(18;27)。该染色体畸变源于牛常染色体18号(BTA18)与27号(BTA27)的串联融合易位，伴随的基因组序列丢失主要发生于BTA18的远端区域及BTA27的近端区域。最终呈现的患病表型包括尿道下裂、生长迟缓与室间隔缺损。