Identification and Characterization of a Genome-wide Significant Region Associated with Red Blood Cell Phenotypes in Domestic Sheep

A genome wide association study (GWAS) investigating red blood cell (RBC) phenotypes was performed with over 500 domestic sheep (Ovis aries) from three economically important breeds in the US (Columbia, Polypay, and Rambouillet). A single nucleotide polymorphism (SNP, hereafter the discovery SNP) showed a high level of association with increased mean corpuscular hemoglobin concentration (MCHC, P =2.66x10^-12) and decreased mean corpuscular volume (MCV, P =5.59x10^-5). Changes in these phenotypes may be indicative of alterations in the morphological structure of RBCs. Additionally, erythrocytes expressing morphologically variant phenotypes often exhibit increased structural fragility, leading to higher turnover rates and increased energy expenditure. The discovery SNP lies in a region containing genes known to play an essential role in membrane organization and formation. To our knowledge, these genes  have not been shown to be involved in the development of morphologically variant RBCs. Preliminary results found additional associations between the discovery SNP and production values, such as ewe lifetime kilograms of lamb weaned (P =2x10^-4). These findings suggest that selection against the minor allele would increase ewe lifetime kilograms of lamb weaned. The minor allele of the discovery SNP was present in all 3 breeds, and is greater than 30% in at least one breed.  These results need to be validated in additional sheep populations, and they provide new candidate genes for RBC morphology in other mammalian systems.