OMIA:001601-9615 : XY DSD (Disorder of Sexual Development), SRY-positive in Canis lupus familiaris |
In other species: horse , domestic cat
Categories: Reproductive system phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2019
Cross-species summary: Renamed from 'Sex reversal: XY female, SRY-positive' [22/10/2021]
Molecular basis: Krzeminska et al. (2019): "The entire coding sequence and flanking regions of the introns, 5′‐UTR and 3′‐UTR [of "six genes of the testosterone pathway, encoding enzymes (CYP17A1, HSD3B2, HSD17B3, SRD5A2) and transcription factors (NR5A1, AR)"] were analyzed in five DSD dogs (78,XY, SRY‐positive) with ambiguous external genitalia and in 15 control dogs. A homozygous deletion of 2 bp in exon 2 of HSD17B3 (hydroxysteroid 17‐beta dehydrogenase 3) was found in a Dachshund dog with enlarged clitoris, vulva and abdominal gonads and decreased serum testosterone level. In silico analysis revealed that this deleterious variant causes truncation of the encoded polypeptide (from 306 to 65 amino acids) and deprivation of the active site of the encoded enzyme. Genotyping of 23 control Dachshund dogs showed a normal homozygous genotype. Thus, we assumed that the 2‐bp deletion is the causative variant."
Krzeminska et al. (2021) "used droplet digital PCR with the aim of determining variability in SRY copy number and its association with DSD in dogs. Altogether 19 DSD male dogs (XY DSD) of 10 breeds and 87 control dogs of eight breeds were analyzed. … Variability of copy number was only observed in Yorkshire Terriers (two or three copies) … . An analysis of six DSD Yorkshire Terriers and 38 control males of this breed showed that 50% of the DSD dogs had two copies, while the incidence of this variant was significantly lower in the control dogs (10.5%). Searching for the copy number of the coding and 5'-flanking fragments revealed full concordance with the copy number. These fragments were also sequenced in DSD (19) and control (24) dogs, and no DNA variants were found. We conclude that, in the dog, two or three functional copies of the SRY gene are present, and a smaller number of copies showed an association with the risk of DSD phenotype in Yorkshire Terriers.”
Breeds: Dachshund, Yorkshire Terrier.
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| HSD17B3 | hydroxysteroid (17-beta) dehydrogenase 3 | Canis lupus familiaris | 1 | NC_006583.2 (73607891..73642437) | HSD17B3 | Homologene, Ensembl , NCBI gene |
Variants
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
| OMIA Variant ID | Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Source of Genetic Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Inferred EVA rsID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1095 | Dachshund | Disorder of sexual development, 78,XY, SRY-positive | HSD17B3 | deletion, small (<=20) | Naturally occurring variant | CanFam3.1 | 1 | g.70554301_70554302del | c.159_160del | p.(T54Wfs*13) | XM_003638870.2; XP_003638918.1; deletion CA | 2019 | 31476086 |
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
| 2022 | Krzeminska, P., Nowacka-Woszuk, J., Switonski, M. : |
| Copy number variation of the SRY gene showed an association with disorders of sex development in Yorkshire Terrier dogs. Anim Genet 53:152-155, 2022. Pubmed reference: 34664728 . DOI: 10.1111/age.13147. | |
| Nowacka-Woszuk, J., Stachowiak, M., Szczerbal, I., Szydlowski, M., Szabelska-Beresewicz, A., Zyprych-Walczak, J., Krzeminska, P., Nowak, T., Lukomska, A., Ligocka, Z., Biezynski, J., Dzimira, S., Nizanski, W., Switonski, M. : | |
| Whole genome sequencing identifies a missense polymorphism in PADI6 associated with testicular/ovotesticular XX disorder of sex development in dogs. Genomics 114:110389, 2022. Pubmed reference: 35597501 . DOI: 10.1016/j.ygeno.2022.110389. | |
| 2019 | Krzeminska, P., Nizanski, W., Nowacka-Woszuk, J., Switonski, M., Krzeminska, P., Nizanski, W., Nowacka-Woszuk, J., Switonski, M. : |
| Analysis of testosterone pathway genes in dogs (78,XY; SRY-positive) with ambiguous external genitalia revealed a homozygous animal for 2-bp deletion causing premature stop codon in HSD17B3. Anim Genet 50:705-711, 2019. Pubmed reference: 31476086 . DOI: 10.1111/age.12850. | |
| 2013 | Dianovský, J., Holečková, B., Hajurka, J., Šiviková, K., Cigánková, V. : |
| Disorder of sexual development in a Yorkshire terrier (78, XY; SRY-positive). J Appl Genet 54:193-9, 2013. Pubmed reference: 23378246 . DOI: 10.1007/s13353-013-0137-1. | |
| 2012 | Switonski, M., Payan-Carreira, R., Bartz, M., Nowacka-Woszuk, J., Szczerbal, I., Colaço, B., Pires, M.A., Ochota, M., Nizanski, W. : |
| Hypospadias in a male (78,XY; SRY-positive) dog and sex reversal female (78,XX; SRY-negative) dogs: clinical, histological and genetic studies. Sex Dev 6:128-34, 2012. Pubmed reference: 21893969 . DOI: 10.1159/000330921. |
Edit History
- Created by Frank Nicholas on 26 Nov 2013
- Changed by Frank Nicholas on 10 Sep 2019
- Changed by Frank Nicholas on 12 Jun 2020
- Changed by Imke Tammen2 on 22 Oct 2021