Institute of Animal Breeding and Genetics, Justus-Liebig-University Gießen, 35390 Gießen, Germany.
Institute of Animal Breeding and Genetics, Justus-Liebig-University Gießen, 35390 Gießen, Germany.
J Dairy Sci. 2019 Jul;102(7):6276-6287. doi: 10.3168/jds.2019-16237. Epub 2019 May 2.
Energy demand for milk production in early lactation exceeds energy intake, especially in high-yielding Holstein cows. Energy deficiency causes increasing susceptibility to metabolic disorders. In addition to several blood parameters, the fat-to-protein ratio (FPR) is suggested as an indicator for ketosis, because a FPR >1.5 refers to high lipolysis. The aim of this study was to analyze phenotypic, quantitative genetic, and genomic associations between FPR and ketosis. In this regard, 8,912 first-lactation Holstein cows were phenotyped for ketosis according to a veterinarian diagnosis key. Ketosis was diagnosed if the cow showed an abnormal carbohydrate metabolism with increased content of ketone bodies in the blood or urine. At least one entry for ketosis in the first 6 wk after calving implied a score = 1 (diseased); otherwise, a score = 0 (healthy) was assigned. The FPR from the first test-day was defined as a Gaussian distributed trait (FPRgauss), and also as a binary response trait (FPRbin), considering a threshold of FPR = 1.5. After imputation and quality controls, 45,613 SNP markers from the 8,912 genotyped cows were used for genomic studies. Phenotypically, an increasing ketosis incidence was associated with significantly higher FPR, and vice versa. Hence, from a practical trait recording perspective, first test-day FPR is suggested as an indicator for ketosis. The ketosis heritability was slightly larger when modeling the pedigree-based relationship matrix (pedigree-based: 0.17; SNP-based: 0.11). For FPRbin, heritabilities were larger when modeling the genomic relationship matrix (pedigree-based: 0.09; SNP-based: 0.15). For FPRgauss, heritabilities were almost identical for both pedigree and genomic relationship matrices (pedigree-based: 0.14; SNP-based: 0.15). Genetic correlations between ketosis with FPRbin and FPRgauss using either pedigree- or genomic-based relationship matrices were in a moderate range from 0.39 to 0.71. Applying genome-wide association studies, we identified the specific SNP rs109896020 (BTA 5, position: 115,456,438 bp) significantly contributing to ketosis. The identified potential candidate gene PARVB in close chromosomal distance is associated with nonalcoholic fatty liver disease in humans. The most important SNP contributing to FPRbin was located within the DGAT1 gene. Different SNP significantly contributed to ketosis and FPRbin, indicating different mechanisms for both traits genomically.
产奶初期的能量需求超过能量摄入，尤其是在高产荷斯坦奶牛中。能量不足会导致代谢紊乱的易感性增加。除了几个血液参数外，脂肪与蛋白质的比值（FPR）也被认为是酮病的一个指标，因为 FPR>1.5 表示脂肪分解增加。本研究的目的是分析 FPR 与酮病之间的表型、数量遗传和基因组关联。为此，根据兽医诊断关键，对 8912 头初产荷斯坦奶牛进行了酮病表型分析。如果奶牛表现出碳水化合物代谢异常，血液或尿液中酮体含量增加，则诊断为酮病。产后 6 周内至少有一次酮病记录表明评分=1（患病）；否则，赋值=0（健康）。将第一次检测日的 FPR 定义为正态分布性状（FPRgauss），并将其定义为二进制响应性状（FPRbin），考虑到 FPR=1.5 的阈值。经过 imputation 和质量控制后，从 8912 头已分型奶牛中使用了 45613 个 SNP 标记进行基因组研究。表型上，酮病发病率的增加与 FPR 的显著升高相关，反之亦然。因此，从实际的性状记录角度来看，首次检测日 FPR 被认为是酮病的一个指标。当用系谱相关矩阵建模时，酮病的遗传力稍大（基于系谱：0.17；基于 SNP：0.11）。对于 FPRbin，当用基因组相关矩阵建模时，遗传力更大（基于系谱：0.09；基于 SNP：0.15）。对于 FPRgauss，基于系谱和基于 SNP 的遗传相关矩阵的遗传力几乎相同（基于系谱：0.14；基于 SNP：0.15）。使用基于系谱或基于基因组的相关矩阵，酮病与 FPRbin 和 FPRgauss 之间的遗传相关性在中等范围内，从 0.39 到 0.71。通过全基因组关联研究，我们鉴定出了位于 BTA5 上的特定 SNP rs109896020（位置：115456438 bp）显著影响酮病。在染色体距离上接近的候选基因 PARVB 与人类的非酒精性脂肪性肝病有关。对 FPRbin 贡献最大的 SNP 位于 DGAT1 基因内。不同的 SNP 对酮病和 FPRbin 有显著贡献，表明这两个性状在基因组上有不同的机制。
