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Title: A divergent artiodactyl MYADM-like repeat is associated with erythrocyte traits and weight of lamb weaned in domestic sheep

item GONZALEZ, MICHAEL - Washington State University
item Mousel, Michelle
item Herndon, David
item JIANG, YU - Commonwealth Scientific And Industrial Research Organisation (CSIRO)
item DALRYMPLE, BRIAN - Commonwealth Scientific And Industrial Research Organisation (CSIRO)
item Reynolds, James
item Johnson, Wendell
item HERRMANN-HOESING, LYNN - Washington State University
item White, Stephen

Submitted to: PLoS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/3/2013
Publication Date: 8/30/2013
Citation: Gonzalez, M.V., Mousel, M.R., Herndon, D.R., Jiang, Y., Dalrymple, B.P., Reynolds, J.O., Johnson, W.C., Herrmann-Hoesing, L.M., White, S.N. 2013. A divergent artiodactyl MYADM-like repeat is associated with erythrocyte traits and weight of lamb weaned in domestic sheep. PLoS One. 8(8):e74700. doi: 10.1371/journal.pone.0074700.

Interpretive Summary: Red blood cell abnormalities cause interruptions in the supply of oxygen and often impair commercial performance of livestock species. A systematic genome-wide scan for genes underlying any red blood cell abnormalities in domestic sheep identified a region on chromosome 18 associated with highly abnormal red blood cells. Strikingly, this same region had recently been shown to have been under very strong selection during the recent evolutionary history of sheep, including the period of domestication and breed formation. Within this genomic region, a copy number variant was identified that resulted in the presence or absence of one complete gene, a member of the MYADM gene family. In addition to red blood cell abnormalities, this copy number variant was also associated with sheep production traits including lifetime weight of lamb weaned, a key measure of ewe productivity and one of the most widely used traits for sheep selective breeding worldwide. These data may help to explain the documented strong historical selection pressure on this gene region. Additional validation data will be needed prior to the use of this copy number variant as a genetic marker for marker-assisted selective breeding, but this finding could result in improved sheep production if validated. Further, to our knowledge this is the first report of any gene in the MYADM family implicated in red blood cell abnormalities in any mammal, so related genes may be important in other species and in human medicine.

Technical Abstract: A genome-wide association study (GWAS) was performed to investigate seven red blood cell (RBC) phenotypes in over 500 domestic sheep (Ovis aries) from three breeds (Columbia, Polypay, and Rambouillet). A single nucleotide polymorphism (SNP) showed genome-wide significant association with increased mean corpuscular hemoglobin concentration (MCHC, P = 6.2 x 10-14) and genome-wide suggestive association with decreased mean corpuscular volume (MCV, P = 2.5 x 10-6). The ovine HapMap project found the same genomic region and the same peak SNP has been under extreme historical selective pressure, demonstrating the importance of this region for survival, reproduction, and/or artificially selected traits. We observed a large (>50 kb) variant haplotype sequence containing a full-length divergent artiodactyl MYADM-like repeat in strong linkage disequilibrium with the associated SNP. MYADM gene family members play roles in membrane organization and formation in myeloid cells. However, to our knowledge, no member of the MYADM gene family has been identified in development of morphologically variant RBCs. The specific RBC differences may be indicative of alterations in morphology. Additionally, erythrocytes with altered morphological structure often exhibit increased structural fragility, leading to increased RBC turnover and energy expenditure. The divergent artiodactyl MYADM-like repeat was also associated with increased ewe lifetime kilograms of lamb weaned (P=2 x 10-4). This suggests selection for normal RBCs might increase lamb weights, although further validation is required before implementation in marker-assisted selection. These results provide clues to explain the strong selection on the artiodactyl MYADM-like repeat locus in sheep, and suggest MYADM family members may be important for RBC morphology in other mammals.