OMIA:001564-9615 : Bleeding disorder, P2RY12-related in Canis lupus familiaris (dog)

Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 609821 (trait) , 600515 (gene)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: ADP response impaired; Postoperative haemorrhage/ hemorrhage, Greater Swiss Mountain dog postoperative haemorrhage

Molecular basis: Boudreaux and Martin and (2011) reported the causal mutation as being "a 3 base-pair deletion predicted to result in elimination of a serine from the extracellular domain was identified in the gene encoding P2RY12, an ADP receptor protein located on platelet membranes". Flores et al. (2017) report a single Greater Swiss Mountain dog that was heterozygous for the P2Y12 receptor gene mutation that developed severe bleeding after surgery. The authors did not exclude compound heterozygosity (presence of a second variant in the same gene). Dogs that are heterozygous for the known P2RY12 mutation may therefore at risk of developing disease, but it remains unclear if this is due to a different mode of inheritance or the existence of a second disease causing variant in the population.

Clinical features: Flores et al. (2017) report that affected dogs have prolonged buccal mucosal bleeding time, tachycardia, pallor, decreased PCV and peritoneal effusion postoperatively. Boudreaux and Martin (2011) suggest that spontaneous haemorrhage is absent to mild in affected dogs but that excessive (and potentially fatal) bleeding can occur after surgical procedures or trauma. Diagnostic tests such as platelet counts, coagulation screening assays (PT & APTT) and von Willebrand factor antigen activity tests have returned as normal in the reported cases (Boudreaux and Martin, 2011). However, flow cytometric studies have shown that affected dogs’ platelets have a markedly reduced response to ADP (Flores et al., 2017). IT thanks DVM student Emily Pratten, who provided the basis of this contribution in May 2023.

Breed: Greater Swiss Mountain Dog (Dog) (VBO_0200631).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
P2RY12 purinergic receptor P2Y, G-protein coupled, 12 Canis lupus familiaris 23 NC_051827.1 (46581332..46535240) P2RY12 Homologene, Ensembl , NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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 Year Published PubMed ID(s) Acknowledgements
454 Greater Swiss Mountain Dog (Dog) Bleeding disorder, P2RY12-related P2RY12 deletion, small (<=20) Naturally occurring variant CanFam3.1 23 g.45909987_45909989del c.516_518del p.(S173del) NM_001003365.1; NP_001003365.1; c.516_518delCTC; "a 3 base-pair deletion predicted to result in elimination of a serine from the extracellular domain was identified in the gene encoding P2RY12" 2011 21554368

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:001564-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

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.

2023 Haginoya, S., Thomovsky, E.J., Johnson, P.A., Brooks, A.C. :
Clinical assessment of primary hemostasis: A review. Top Companion Anim Med 56-57:S1938-9736(23)00058-2:100818, 2023. Pubmed reference: 37673175. DOI: 10.1016/j.tcam.2023.100818.
Meadows, J.R.S., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., Hitte, C., Nguyen, A.K., Wang, C., Jagannathan, V., Niskanen, J.E., Frantz, L.A.F., Arumilli, M., Hundi, S., Lindblad-Toh, K., Ginja, C., Agustina, K.K., André, C., Boyko, A.R., Davis, B.W., Drögemüller, M., Feng, X.Y., Gkagkavouzis, K., Iliopoulos, G., Harris, A.C., Hytönen, M.K., Kalthoff, D.C., Liu, Y.H., Lymberakis, P., Poulakakis, N., Pires, A.E., Racimo, F., Ramos-Almodovar, F., Savolainen, P., Venetsani, S., Tammen, I., Triantafyllidis, A., vonHoldt, B., Wayne, R.K., Larson, G., Nicholas, F.W., Lohi, H., Leeb, T., Zhang, Y.P., Ostrander, E.A. :
Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 24:187, 2023. Pubmed reference: 37582787. DOI: 10.1186/s13059-023-03023-7.
Van Vertloo, L.R., Portanova, A.Z., Donnini, E.K., Hale, A.S., LeVine, D.N. :
Prophylactic use of a lyophilized platelet product for rhinoscopic diagnosis and treatment of sinonasal aspergillosis in a dog with a P2Y12 platelet receptor mutation. J Vet Emerg Crit Care (San Antonio) , 2023. Pubmed reference: 36815741. DOI: 10.1111/vec.13284.
2017 Flores, R.S., Boudreaux, M.K., Vasquez, B., Bristow, P., Aronson, L.R., Santoro-Beer, K., Callan, M.B. :
Heterozygosity for P2Y12 receptor gene mutation associated with postoperative hemorrhage in a Greater Swiss Mountain dog. Vet Clin Pathol 46:569-574, 2017. Pubmed reference: 28800150. DOI: 10.1111/vcp.12533.
2011 Boudreaux, MK., Martin, M. :
P2Y12 receptor gene mutation associated with postoperative hemorrhage in a Greater Swiss Mountain dog. Vet Clin Pathol 40:202-206, 2011. Pubmed reference: 21554368. DOI: 10.1111/j.1939-165X.2011.00318.x.

Edit History


  • Created by Frank Nicholas on 12 May 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 23 Apr 2013
  • Changed by Frank Nicholas on 17 Jun 2013
  • Changed by Frank Nicholas on 05 Mar 2017
  • Changed by Imke Tammen2 on 11 Mar 2023
  • Changed by Imke Tammen2 on 08 Jun 2023
  • Changed by Imke Tammen2 on 22 May 2024