In other species: domestic cat , llama , cattle

Categories: Haematopoietic system phene

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

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Somatic mutation

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2011

Cross-species summary: also known as erythrocytosis, high concentration of red blood cells in the blood

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.

The authors suggested that the mutations were acquired as somatic mutations (genetic mosaicism) based on differences in sequencing results in DNA extracted from blood and a buccal swab.

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: