Lameness in dairy cattle is primarily caused by foot lesions including the claw horn lesions (CHL) of sole haemorrhage (SH), sole ulcers (SU), and white line disease (WL). This study investigated the genetic architecture of the three CHL based on detailed animal phenotypes of CHL susceptibility and severity. Estimation of genetic parameters and breeding values, single-step genome-wide association analyses, and functional enrichment analyses were performed. The studied traits were under genetic control with a low to moderate heritability. Heritability estimates of SH and SU susceptibility on the liability scale were 0.29 and 0.35, respectively. Heritability of SH and SU severity were 0.12 and 0.07, respectively. Heritability of WL was relatively lower, indicating stronger environmental influence on the presence and development of WL than the other two CHL. Genetic correlations between SH and SU were high (0.98 for lesion susceptibility and 0.59 for lesion severity), whereas genetic correlations of SH and SU with WL also tended to be positive. Candidate quantitative trait loci (QTL) were identified for all CHL, including some on Bos taurus chromosome (BTA) 3 and 18 with potential pleiotropic effects associated with multiple foot lesion traits. A genomic window of 0.65 Mb on BTA3 explained 0.41, 0.50, 0.38, and 0.49% of the genetic variance for SH susceptibility, SH severity, WL susceptibility, and WL severity, respectively. Another window on BTA18 explained 0.66, 0.41, and 0.70% of the genetic variance for SH susceptibility, SU susceptibility, and SU severity, respectively. The candidate genomic regions associated with CHL harbour annotated genes that are linked to immune system function and inflammation responses, lipid metabolism, calcium ion activities, and neuronal excitability. The studied CHL are complex traits with a polygenic mode of inheritance. Most traits exhibited genetic variation suggesting that animal resistance to CHL can be improved with breeding. The CHL traits were positively correlated, which will facilitate genetic improvement for resistance to CHL as a whole. Candidate genomic regions associated with lesion susceptibility and severity of SH, SU, and WL provide insights into a global profile of the genetic background underlying CHL and inform genetic improvement programmes aiming at enhancing foot health in dairy cattle.

中文翻译：

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使用线性和阈值模型对荷斯坦牛爪角病变进行单步全基因组关联分析

奶牛的跛行主要由足部病变引起，包括蹄部出血 (SH) 的爪角病变 (CHL)、足底溃疡 (SU) 和白线病 (WL)。本研究基于 CHL 易感性和严重程度的详细动物表型，研究了三种 CHL 的遗传结构。进行了遗传参数和育种值的估计、单步全基因组关联分析和功能富集分析。所研究的性状受遗传控制，具有低到中等的遗传力。SH 和 SU 易感性在责任等级上的遗传力估计值分别为 0.29 和 0.35。SH 和 SU 严重程度的遗传力分别为 0.12 和 0.07。WL的遗传力相对较低，表明环境对 WL 的存在和发展的影响比其他两种 CHL 更强。SH 和 SU 之间的遗传相关性很高（病变易感性为 0.98，病变严重性为 0.59），而 SH 和 SU 与 WL 的遗传相关性也趋于正相关。为所有 CHL 确定了候选数量性状位点 (QTL)，包括 Bos taurus 染色体 (BTA) 3 和 18 上的一些，具有与多足部病变特征相关的潜在多效性。BTA3 上 0.65 Mb 的基因组窗口分别解释了 SH 易感性、SH 严重性、WL 易感性和 WL 严重性的遗传变异的 0.41%、0.50%、0.38% 和 0.49%。BTA18 的另一个窗口分别解释了 SH 易感性、SU 易感性和 SU 严重性的遗传变异的 0.66%、0.41% 和 0.70%。与 CHL 相关的候选基因组区域包含与免疫系统功能和炎症反应、脂质代谢、钙离子活性和神经元兴奋性相关的注释基因。所研究的 CHL 是具有多基因遗传模式的复杂性状。大多数性状表现出遗传变异，表明动物对 CHL 的抗性可以通过育种提高。CHL 性状呈正相关，这将有助于整体上对 CHL 抗性的遗传改良。与 SH、SU 和 WL 的病变易感性和严重性相关的候选基因组区域提供了对 CHL 遗传背景全球概况的深入了解，并为旨在增强奶牛足部健康的遗传改良计划提供了信息。