title: A divergent Artiodactyl MYADM-like repeat is associated with erythrocyte traits and weight of lamb weaned in domestic sheep.
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 = 6.2×10(-14)) and genome-wide suggestive association with decreased mean corpuscular volume (MCV, P = 2.5×10(-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 = 2×10(-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.
authors.affiliation: Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, Washington, United States of America ; Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, United States of America.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Gonzalez
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Mousel
authors.forename: David R
authors.initials: DR
authors.lastname: Herndon
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.forename: Brian P
authors.initials: BP
authors.lastname: Dalrymple
authors.forename: James O
authors.initials: JO
authors.lastname: Reynolds
authors.forename: Wendell C
authors.initials: WC
authors.lastname: Johnson
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Herrmann-Hoesing
authors.forename: Stephen N
authors.initials: SN
authors.lastname: White
mesh_terms: D000483:Alleles; D000818:Animals; D001835:Body Weight / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics; D004909:Erythrocyte Indices / Q000235:genetics; D004912:Erythrocytes; D005787:Gene Frequency / Q000235:genetics; D016678:Genome / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D034561:Sheep, Domestic / Q000235:genetics*; D014886:Weaning
chemical_list: D006454:Hemoglobins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins
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