A single missense mutation at position 159 of COQ9 (G→A; rs109301586) has been associated with genetic variation in fertility in Holstein cattle, with the A allele associated with higher fertility. COQ9 is involved in the synthesis of coenzyme COQ10, a component of the electron transport system of the mitochondria. Here we tested whether reproductive phenotype is associated with the mutation and evaluated functional consequences for cellular oxygen metabolism, body weight changes, and ovarian function. The mutation in COQ9 modifies predicted tertiary protein structure and affected mitochondrial respiration of peripheral blood mononuclear cells. The A allele was associated with low resting oxygen consumption and high electron transport system capacity. Phenotypic measurements for fertility were evaluated for up to five lactations in a population of 2273 Holstein cows. There were additive effects of the mutation (P < 0.05) in favor of the A allele for pregnancy rate (+3%), interval from calving to conception (-8 d), and services per conception (-0.2). There was no association of genotype with milk production or body weight changes postpartum. The mutation in COQ9 affected ovarian function; the A allele was associated with increased mitochondrial DNA copy number in oocytes, and there were overdominance effects for COQ9 expression in oocytes, follicle number and AMH concentrations. Overall, results show how a gene involved in mitochondrial function is associated with overall fertility, possibly in part by affecting oocyte quality.

Research was supported by Agriculture and Food Research Initiative Competitive Grant no. 2013-68004-20365 from the USDA National Institute of Food and Agriculture and a grant from the Southeast Milk Inc. Milk Check-off Program. Cole and Null were supported by appropriated project 1265-31000-096-00, “Improving Genetic Predictions in Dairy Animals Using Phenotypic and Genomic Information”, of the Agricultural Research Service of the United States Department of Agriculture.

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