OMIA 000809-9615 : Polycythemia in Canis lupus familiaris

In other species: domestic cat , llama , cattle

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 133100 , 263300

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2011

Molecular basis: Using the comparative candidate gene strategy (based on the same clinical signs in humans being due to mutations in the JAK2 gene), Beurlet et al. (2011) sequenced exon 14 of the canine JAK2 gene in five affected dogs (a female "crossbred", a male Maltese, a female Poodle, a female Yorkshire, and a female "Westie") and discovered a possible causal triple-mutation variant (c.1849G>T, c.1852T>C, c.1853G>T; p.V617F, p.C618L) in just one dog (the "crossbred"), the other four having only wild-type sequence. Evidence that this variant is likely to be causal was based on (a) This same variant (at the peptide level) is causal in humans; and (b) "Transfection of BaF3 cells with the triple mutant cDNA, but not with the wild-type complementary DNA, resulted in cytokine-independent growth and constitutive signal transducer and activation of transcription 5 phosphorylation". As the authors note, the fact that four of the five affected dogs do not have the likely causal variant indicates that "we cannot exclude the presence of different mutations of JAK2 or mutations of proteins upstream or downstream of JAK2. . . . alternate mutations may be found in JAK-STAT regulating pathways, such as reported in the LNK gene [in humans]". The fact that the five sequenced dogs are a cross between un-named breeds and one each of four different breeds, explains why the likely causal variant was seen in only one dog. Given the lack of knowledge of the breeds involved in the crossbred dog, and the lack of the likely causal variant in the other four dogs, it can be concluded that testing for this particular variant will not be particularly effective in any breed until further information is obtained on the distribution and effect of this variant.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
JAK2 Janus kinase 2 Canis lupus familiaris 1 NC_006583.3 (93321055..93438898) JAK2 Homologene, Ensembl, NCBI gene

Variants

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Polycythemia JAK2 complex rearrangement c.1849G>T, c.1852T>C, c.1853G> p.V617F, p.C618L a three-base change in codons 617 and 618 of JAK2 giving rise to V617F and C618L 2011 21320566

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.
2011 Beurlet, S., Krief, P., Sansonetti, A., Briend-Marchal, A., Kiladjian, JJ., Padua, RA., Chomienne, C., Cassinat, B. :
Identification of JAK2 mutations in canine primary polycythemia. Exp Hematol 39:542-5, 2011. Pubmed reference: 21320566. DOI: 10.1016/j.exphem.2011.02.003.
1998 Faissler, D., Griotwenk, M.E., Fatzer, R., Vontscharner, C., Aberlethiemann, B., Jaggy, A. :
Seizures due to polycythemia - review of literature and case report [Review] [German] Schweizer Archiv fur Tierheilkunde 140:101-109, 1998. Pubmed reference: 9528346.
1997 Vanvonderen, I.K., Meyer, H.P., Kraus, J.S., Kooistra, H.S. :
Polyuria and polydipsia and disturbed vasopressin release in 2 dogs with secondary polycythemia Journal of Veterinary Internal Medicine 11:300-303, 1997. Pubmed reference: 9348498.
1959 Donovan, E.F., Loeb, W.F. :
Polycythemia rubra vera in the dog Journal of the American Veterinary Medical Association 134:36-37, 1959. Pubmed reference: 13610760.

Edit History


  • Created by Frank Nicholas on 03 Jul 2011
  • Changed by Frank Nicholas on 28 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 28 Mar 2017