Department of Animal Science, Cornell University, Ithaca, NY 14853.
Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj 77871-31587, Iran.
J Dairy Sci. 2020 Apr;103(4):3289-3303. doi: 10.3168/jds.2019-17409. Epub 2020 Feb 7.
The bovine digital cushion is a compression pad between the distal phalanx and sole and has been associated with claw horn disruption lesions. Digital cushion thickness (DCT) is estimated to be moderately heritable. Therefore, the objectives of our study were to examine influences of management and environment on DCT and to identify genetic markers and candidate genes associated with DCT. In a cohort of 502 Holsteins from 5 farms in New York State, DCT and body condition score (BCS) were collected twice, at <137 d prepartum and from 86 to 127 d in milk, corresponding to periods when the digital cushion is thickest and thinnest, respectively, as determined by previous research. Cows underwent sonographic examination of the digital cushion evaluated at the typical sole ulcer site for the right front and hind foot. Linear mixed models were conducted on DCT with the fixed effects of time point, digit, wither height, sacral height, BCS group, and multiple farm system variables separately and included random effects to control for the random subset of cows per farm, repeated measures, and multiple measurements from each cow. The phenotypic results indicated that DCT varied by sample time point, sacral height, parity, digit, BCS group, and wither height. For the genotypic study, 447 DNA samples were genotyped on the Illumina BovineHD 777K BeadChip (Illumina Inc., San Diego, CA). Quality assessment of markers and samples provided a final data set of 431 samples and 579,449 markers. Genome-wide association studies were conducted for DCT testing inheritance models and genetic variation of digit, foot, time point, and average thickness. One marker passed the Bonferroni correction threshold and 26 passed false discovery rate from 4 genome-wide association studies with covariates of sequencing batch plate, parity group, BCS, wither height, and sacral height. Ten candidate genes were identified, with 2 genes on Bos taurus autosomes 24 and 29 involved in biological functions related to the digital cushion: MC4R and DLG2 were related to fat deposition and bone growth, respectively. The genetic markers discovered in this study have the opportunity to be used in breeding programs using genomic selection to select against claw horn disruption lesions and lameness due to associations between the markers and DCT. Further studies on the biologically plausible candidate genes may identify causative genetic variants and how they relate to DCT through gene regulation, expression, structure, or copy number variation.
牛的数字垫是位于远指（趾）骨和鞋底之间的压缩垫，与爪角破坏病变有关。数字垫厚度（DCT）被估计具有中度的遗传性。因此，我们的研究目的是检查管理和环境对 DCT 的影响，并确定与 DCT 相关的遗传标记和候选基因。在纽约州 5 个农场的 502 头荷斯坦牛的队列中，在产前 <137 天和产奶后 86-127 天两次采集 DCT 和体况评分（BCS），分别对应于数字垫最厚和最薄的时期，如先前的研究确定的那样。对右前肢和后肢的典型鞋底溃疡部位进行了数字垫的超声检查。采用线性混合模型对 DCT 进行分析，固定效应包括时间点、数字、肩高、荐骨高、BCS 组和多个农场系统变量，随机效应包括每个农场的随机子集、重复测量和每个牛的多次测量。表型结果表明，DCT 随采样时间点、荐骨高、胎次、数字、BCS 组和肩高而变化。对于基因型研究，对 447 个 DNA 样本进行了 Illumina BovineHD 777K BeadChip（Illumina Inc.，圣地亚哥，CA）的基因分型。标记和样本的质量评估提供了最终的数据集，包括 431 个样本和 579449 个标记。进行了全基因组关联研究，以检测 DCT 测试的遗传模型和数字、脚、时间点和平均厚度的遗传变异。有 1 个标记通过了 Bonferroni 校正阈值，有 26 个标记通过了包含测序批次板、胎次组、BCS、肩高和荐骨高的 4 个全基因组关联研究的错误发现率。确定了 10 个候选基因，其中 2 个基因位于牛 24 号和 29 号染色体上，与数字垫有关的生物学功能相关：MC4R 和 DLG2 分别与脂肪沉积和骨骼生长有关。在这项研究中发现的遗传标记有机会通过基因组选择在育种计划中使用，以选择与爪角破坏病变和跛行相关的标记和 DCT。对生物学上合理的候选基因的进一步研究可能会确定因果遗传变异，以及它们如何通过基因调控、表达、结构或拷贝数变异与 DCT 相关。
