Location: Animal Disease ResearchTitle: Identification and characterization of a genome-wide significant region associated with red blood cell phenotypes in domestic sheep Author
|Johnson, W Carl - Carl|
|Knowles, Donald - Don|
Submitted to: Annual International Plant & Animal Genome Conference
Publication Type: Abstract Only
Publication Acceptance Date: 11/13/2012
Publication Date: 12/1/2012
Citation: Gonzalez, M.V., Mousel, M.R., Reynolds, J.O., Johnson, W.C., Herrmann-Hoesing, L.M., Lewis, G.S., Knowles Jr, D.P., White, S.N. 2012. Identification and characterization of a genome-wide significant region associated with red blood cell phenotypes in domestic sheep. Annual International Plant & Animal Genome Conference. Plant & Animal Genomes Conference XXI, Abstract 0617. San Diego, CA. January 14, 2013.. Interpretive Summary: Red blood cell (RBC) traits were examined in more than 500 domestic sheep from three economically important breeds in the US using an approach to scan all sheep chromosomes for the locations of important genes. One single nucleotide polymorphism (SNP, hereafter the discovery SNP) was associated with increased concentration of hemoglobin in each RBC and decreased volume of each RBC. The discovery SNP lies in a region containing genes known to play an essential role in membrane organization and formation. To our knowledge, this is the first report of these genes playing a role in the development of RBCs of differing shape and structure. Further, the observed characteristics may be indicative of altered shape of RBCs, which often makes them more fragile. Since fragile cells require frequent replacement, this can lead to an energy drain for making replacement cells. Additional preliminary results suggest that the discovery SNP is associated with decreased sheep production, including decreased lifetime weight of lambs weaned, one of the most widely used breeding criteria in domestic sheep. This is consistent with the energy drain expected from fragile RBCs. Additional work will be needed to produce a DNA test for breeding sheep without the fragile RBCs, but such a test may improve not only the blood but also total economic output from sheep flocks.
Technical Abstract: 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.