Prevalence of the AMHR2 mutation in Miniature Schnauzers and genetic investigation of a Belgian Malinois with persistent Müllerian duct syndrome

• Published in: Reproduction in domestic animals Vol. 53; no. 2; pp. 371 - 376
• Main Authors: Smit, MM, Ekenstedt, KJ, Minor, KM, Lim, CK, Leegwater, PAJ, Furrow, E
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01-04-2018
• Subjects: Alleles; Animals; Breeding; Cancer; Codon, Nonsense; Complications; Cryptorchidism; Deoxyribonucleic acid; Disorder of Sex Development, 46,XY - epidemiology; Disorder of Sex Development, 46,XY - genetics; Disorder of Sex Development, 46,XY - veterinary; DNA; dog; Dog Diseases - epidemiology; Dog Diseases - genetics; Dogs; Ducts; Embryos; Exons; Gene frequency; Genetic screening; Genetic Testing - veterinary; Genetics < General reproduction; Health risks; Infertility; Male; Males; Miniature Schnauzer; Muellerian duct; Mutation; Nonsense mutation; Nucleotide sequence; Persistent Mullerian duct syndrome; Prevalence; Receptors, Peptide - genetics; Receptors, Transforming Growth Factor beta - genetics; Reproductive system; Sequence Analysis, DNA; Splicing; Testicular cancer; Persistent Mullerian duct syndrome; Miniature Schnauzer; dog; Genetics < General reproduction
• ISSN: 0936-6768; 1439-0531
• DOI: 10.1111/rda.13116

Contents
Persistent Müllerian duct syndrome (PMDS) is a sex‐limited disorder in which males develop portions of the female reproductive tract. Important consequences of PMDS are cryptorchidism and its sequelae of infertility and increased risk of testicular cancer. Anti‐Müllerian hormone (AMH) and its receptor (AMHR2) induce the regression of the Müllerian ducts in male embryos. In Miniature Schnauzer dogs, the genetic basis has been identified as an autosomal recessive nonsense mutation in AMHR2, but the allele frequency of the mutation is unknown. Thus, the primary objective of this study was to estimate the prevalence of the AMHR2 mutation in North American Miniature Schnauzers, in order to ascertain the value of genetic testing in this breed. An additional objective was to determine whether mutations in AMH or AMHR2 were responsible for PMDS in a Belgian Malinois; this would aid development of a genetic test for the Belgian Malinois breed. Genomic DNA from 216 Miniature Schnauzers (including one known PMDS case) was genotyped for the AMHR2 mutation, and DNA from a single PMDS‐affected Belgian Malinois was sequenced for all coding exons of AMH and AMHR2. The Miniature Schnauzer cohort had an AMHR2 mutation allele frequency of 0.16 and a carrier genotypic frequency of 0.27. The genetic basis for PMDS in the Belgian Malinois was not determined, as no coding or splicing mutations were identified in either AMH or AMHR2. These findings support a benefit to AMHR2 mutation testing Miniature Schnauzers used for breeding or with cryptorchidism.