Using sheep genomes from diverse U.S. breeds to identify missense variants in genes affecting fecundity

Abstract

<i>Background</i>: Access to sheep genome sequences significantly improves the chances of identifying genes that may influence the health, welfare, and productivity of these animals. <i>Methods</i>: A public, searchable DNA sequence resource for U.S. sheep was created with whole genome sequence (WGS) of 96 rams. The animals shared minimal pedigree relationships and represent nine popular U.S. breeds and a composite line. The genomes are viewable online with the user-friendly Integrated Genome Viewer environment, and may be used to identify and decode gene variants present in U.S. sheep. <i>Results</i>: The genomes had a combined average read depth of 16, and an average WGS genotype scoring rate and accuracy exceeding 99%. The utility of this resource was illustrated by characterizing three genes with 14 known coding variants affecting litter size in global sheep populations: growth and differentiation factor 9 ( <i>GDF9),</i> bone morphogenetic protein 15 ( <i>BMP15</i>), and bone morphogenetic protein receptor 1B ( <i>BMPR1B</i>). In the 96 U.S. rams, nine missense variants encoding 11 protein variants were identified. However, only one was previously reported to affect litter size ( <i>GDF9</i> V371M, Finnsheep). Two missense variants in <i>BMP15</i> were identified that had not previously been reported: R67Q in Dorset, and L252P in Dorper and White Dorper breeds. Also, two novel missense variants were identified in <i>BMPR1B</i>: M64I in Katahdin, and T345N in Romanov and Finnsheep breeds. Based on the strict conservation of amino acid residues across placental mammals, the four variants encoded by <i>BMP15</i> and <i>BMPR1B</i> are predicted to interfere with their function. However, preliminary analyses of litter sizes in small samples did not reveal a correlation with variants in <i>BMP15</i> and <i>BMPR1B</i> with daughters of these rams. <i>Conclusions</i>: Collectively, this report describes a new resource for discovering protein variants <i>in silico</i> and identifies alleles for further testing of their effects on litter size in U.S. breeds.