Centre for Genetic Improvement of Livestock (CGIL), Department of Animal Biosciences, University of Guelph, Guelph, Ontario, Canada, N1G 2W1; The Semex Alliance, Guelph, Ontario, Canada, N1G 3Z2.
Centre for Genetic Improvement of Livestock (CGIL), Department of Animal Biosciences, University of Guelph, Guelph, Ontario, Canada, N1G 2W1.
J Dairy Sci. 2018 Aug;101(8):7248-7257. doi: 10.3168/jds.2017-13848. Epub 2018 May 10.
Superovulation or ovum pick-up and in vitro fertilization are technologies used to produce an increased number of embryos from elite females. Embryo production traits have been shown to be heritable, but the genes that cause this variability have not yet been assessed. The main objectives of this study were to perform a genome-wide association study (GWAS) to find single nucleotide polymorphisms (SNP) associated with embryo production traits and to identify candidate genes affecting the number of embryos produced by Holstein donors in Canada that may provide insight into the regulation of embryo production. Breeding values were estimated and de-regressed for all donors and sires using a data set of 150,971 records of superovulation or ovum pick-up and in vitro fertilization. A total of 11,607 animals were genotyped, but of that number only 5,118 were genotyped with at least a 50K SNP panel and had a de-regressed estimated breeding value reliability of at least 10%. For the GWAS, 606,406 imputed SNP on 29 autosomal chromosomes were considered after applying quality control measures. A single-SNP univariate mixed linear animal model was used to perform the GWAS, and a 5% false discovery rate was applied to adjust for multiple testing. We found 36 and 14 significant SNP associated with the total number of embryos and the number of viable embryos, respectively, with most of them located on chromosome 11. Using these significant SNP, positional genes located within 10,000 bp upstream and downstream of the SNP were retrieved. Thirteen genes were harboring or near the significant SNP for the total number of embryos, 4 of them also being near the significant SNP for viable embryos. Some of these genes (CRB2, DENND1A, MAD1L1, NDUFA8, PTGS1) could be considered as potential positional candidate genes related to the number of embryos produced by a donor. This list will need to be validated in an independent population to confirm the role of the genes for embryo production.
超数排卵或卵母细胞采集和体外受精是用于从优秀雌性生产出更多胚胎的技术。已经证明胚胎生产性状是可遗传的，但导致这种变异性的基因尚未得到评估。本研究的主要目的是进行全基因组关联研究（GWAS），以找到与胚胎生产性状相关的单核苷酸多态性（SNP），并确定影响加拿大荷斯坦供体生产胚胎数量的候选基因，这些基因可能为胚胎生产的调控提供启示。使用超数排卵或卵母细胞采集和体外受精的 150971 个记录数据集，对所有供体和种公牛进行了育种值估计和去回归。共对 11607 头动物进行了基因分型，但其中只有 5118 头动物使用至少 50K SNP 面板进行了基因分型，且去回归估计育种值可靠性至少为 10%。对于 GWAS，在应用质量控制措施后，考虑了 29 条常染色体上的 606406 个导入 SNP。使用单 SNP 单变量混合线性动物模型进行 GWAS，并应用 5%的错误发现率（FDR）来调整多重检验。我们发现 36 个和 14 个 SNP 分别与总胚胎数和可存活胚胎数显著相关，大多数 SNP 位于第 11 号染色体上。使用这些显著 SNP，检索到位于 SNP 上下游 10000bp 内的位置基因。有 13 个基因携带或靠近总胚胎数的显著 SNP，其中 4 个基因也靠近可存活胚胎数的显著 SNP。其中一些基因（CRB2、DENND1A、MAD1L1、NDUFA8、PTGS1）可以被认为是与供体生产胚胎数量相关的潜在位置候选基因。需要在独立的群体中验证这一列表，以确认这些基因在胚胎生产中的作用。
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