Persistent Mullerian duct syndrome in dogs: a new insight into organization of AMH and AMHR2 genes

Abstract

Persistent Mullerian Duct Syndrome (PMDS) is a rare congenital disorder in males, characterized by the presence of Mullerian duct derivatives despite normal testes and external genitalia. This condition is typically linked to a dysfunction in the anti-Mullerian hormone (AMH) or its receptor (AMHR2), both of which are critical for the regression of the Mullerian ducts. In dogs, PMDS is particularly frequent in the Miniature Schnauzer breed, although cases have also been reported in other breeds, such as the Yorkshire Terrier. To date, a single causative variant has been identified in the AMHR2 gene, but only in Miniature Schnauzers. No deleterious variants have been found in the AMH gene; however, with the exception of one report, most studies have not sequenced the entire exon 5. This study provides novel insights into the genomic organization of canine AMH and AMHR2 genes through bioinformatics and in silico analyses of previously reported whole-genome sequencing (WGS) data from a Yorkshire Terrier affected by PMDS. The results indicate that current canine genome assemblies (ROS_Cfam_1.0; CanFam4, and CanFam6) contain a complete reference sequence for the AMH gene, unlike the earlier CanFam3.1 genome. However, next-generation sequencing technologies (WGS and RNA-seq) face challenges due to technical limitations in analyzing GC-rich repetitive elements present in exon 5 of canine AMH gene. In contrast, the genomic structure of the AMHR2 gene remains inaccurately represented in the current ROS_Cfam_1.0 genome (eight instead of eleven exons), while both CanFam4 and CanFam6 contain additional and unknown nucleotide/amino acid sequences. The CanFam3.1 genome assembly still provides the most accurate annotation for canine AMHR2 gene. Based on these findings, re-sequencing of the AMH gene in previously reported dogs affected by PMDS using the methodology proposed in recent literature is recommended. Further attention should be given to comparative analyses to assess whether the dogs genome contains accurate information about genes or proteins that correspond to human orthologs.