Association Analysis of Potassium-Chloride Cotransporter Variants and Sheep Erythrocyte Potassium

Sheep exhibit a dimorphism in erythrocyte potassium content with large differences between “low” and “high” potassium phenotypes, and this dimorphism shows evidence for Mendelian inheritance. In addition, the low potassium characteristic has been associated with fine wool production. While the exact basis for this dimorphism has not been completely elucidated, the phenotypes have been associated with activity level differences in erythrocytic potassium-chloride cotransporters (KCC). KCC are electrolyte transport proteins involved in regulation of cell volume. They are encoded by multiple genes, and the KCC1 and KCC3 proteins are found on sheep erythrocytes. However, no studies to date have attempted to characterize the specific mutation responsible. We hypothesized that common variants in the genes encoding KCC1 (SLC12A4) and KCC3 (SLC12A6) account for known differences in sheep erythrocytic potassium levels. We genotyped 124 Rambouillet, Polypay, and Suffolk sheep with divergent erythrocyte potassium concentrations and examined association between the SNP variants and erythrocyte potassium content while accounting for breed. To date, no significant differences in potassium concentration have been found for examined SNP variants. However, work is ongoing to identify the mutation responsible for the sheep erythrocyte potassium dimorphism.