The Characterization of a Divergent Artiodactyl MYADM-like Repeat Associated with Erythrocyte Traits and Weight of Lamb Weaned in Domestic Sheep

The ovine HapMap project identified a small number of single nucleotide polymorphisms (SNP) under extreme historical selective pressure, demonstrating the importance of these regions for survival, reproduction, and/or artificially selected traits. A recent genome-wide association study (GWAS) identified one of these SNPs from a scantily characterized region that was highly associated with multiple red blood cell (RBC) phenotypes. This SNP was located within an expanded repeat locus containing approximately 40 MYADM-like repeats of varying length, and the overall expanded repeat locus has been observed only in the artiodactyl lineage. Within this region, we observed a large (>50 Kbp in the reference sheep genome) divergent haplotype sequence containing a single full-length divergent artiodactyl MYADM-like repeat in strong linkage disequilibrium with the associated SNP. MYADM gene family members have roles in membrane organization and formation in myeloid cells. However, to our knowledge, no member of the MYADM gene family had been linked with RBC phenotypes. The divergent artiodactyl MYADM-like repeat was also associated with increased ewe lifetime kilograms of lamb weaned (P = 2x10^-4), which may explain strong historical selection. Here, we report current progress toward characterizing this locus. We have sequenced approximately 1,300 base pairs within the alternate allele, but much of the alternate allele remains uncharacterized. A bacterial artificial chromosome (BAC) clone has been identified that appears to contain the full-length alternate allele for the region of interest. BAC sequencing is underway and should clarify the complex genetic architecture of this locus in domestic sheep.