Ortega M Sofia, Wohlgemuth Stephanie, Tribulo Paula, Siqueira Luiz G B, Cole John B, Hansen Peter J
Department of Animal Sciences, University of Florida, Gainesville, Florida, USA.
Embrapa Gado de Leite, Juiz de Fora, Minas Gerais, Brazil.
Biol Reprod. 2017 Mar 1;96(3):652-663. doi: 10.1093/biolre/iox004.
A single missense mutation at position 159 of coenzyme Q9 (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, interval from calving to conception, and services per conception. 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 antimullerian hormone concentrations. Overall, results show how a gene involved in mitochondrial function is associated with overall fertility, possibly in part by affecting oocyte quality.
辅酶Q9（COQ9）第159位的单个错义突变（G→A；rs109301586）与荷斯坦奶牛生育力的遗传变异有关，A等位基因与较高的生育力相关。COQ9参与辅酶COQ10的合成，COQ10是线粒体电子传递系统的一个组成部分。在此，我们测试了生殖表型是否与该突变相关，并评估了其对细胞氧代谢、体重变化和卵巢功能的功能影响。COQ9中的突变改变了预测的蛋白质三级结构，并影响外周血单核细胞的线粒体呼吸。A等位基因与低静息氧消耗和高电子传递系统能力相关。在2273头荷斯坦奶牛群体中，对多达五个泌乳期的生育力表型测量进行了评估。该突变存在有利于A等位基因的加性效应（P < 0.05），涉及妊娠率、产犊至受孕间隔和每次受孕所需配种次数。基因型与产奶量或产后体重变化无关。COQ9中的突变影响卵巢功能；A等位基因与卵母细胞中线粒体DNA拷贝数增加相关，并且在卵母细胞中COQ9表达、卵泡数量和抗缪勒氏管激素浓度方面存在超显性效应。总体而言，结果表明参与线粒体功能的一个基因如何与整体生育力相关，可能部分是通过影响卵母细胞质量实现的。
