BACKGROUND Ketosis in dairy cattle has been shown to cause a high morbidity in the farm and substantial financial losses to dairy farmers. Ketosis symptoms, however, are difficult to identify, therefore, the amount of ketone bodies (mainly β-hydroxybutyric acid, BHB) is used as an indicator of subclinical ketosis in cows. It has also been shown that milk BHB concentrations have a strong correlation with ketosis in dairy cattle. Mid-infrared spectroscopy (MIR) has recently became a fast, cheap and high-throughput method for analyzing milk components. The aim of this study was to perform a genome-wide association study (GWAS) on the MIR-predicted milk BHB to identify genomic regions, genes and pathways potentially affecting subclinical ketosis in North American Holstein dairy cattle. RESULTS Several significant regions were identified associated with MIR-predicted milk BHB concentrations (indicator of subclinical ketosis) in the first lactation (SCK1) and second and later lactations (SCK2) in Holstein dairy cows. The strongest association was located on BTA6 for SCK1 and BTA14 on SCK2. Several SNPs on BTA6 were identified in regions and variants reported previously to be associated with susceptibility to ketosis and clinical mastitis in Jersey and Holstein dairy cattle, respectively. One highly significant SNP on BTA14 was found within the DGAT1 gene with known functions on fat metabolism and inflammatory response in dairy cattle. A region on BTA6 and three SNPs on BTA20 were found to overlap between SCK1 and SCK2. However, a novel region on BTA20 (55-63 Mb) for SCK2 was also identified, which was not reported in previous association studies. Enrichment analysis of the list of candidate genes within the identified regions for MIR-predicted milk BHB concentrations yielded molecular functions and biological processes that may be involved in the inflammatory response and lipid metabolism in dairy cattle. CONCLUSIONS The results of this study confirmed several SNPs and genes identified in previous studies as associated with ketosis susceptibility and immune response, and also found a novel region that can be used for further analysis to identify causal variations and key regulatory genes that affect clinical/ subclinical ketosis.

中文翻译：

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全基因组关联分析荷斯坦奶牛牛奶中β-羟基丁酸酯的浓度。

背景技术已经证明，奶牛中的酮症会引起农场中的高发病率，并给奶农带来巨大的经济损失。但是，酮症的症状很难识别，因此，酮体（主要是β-羟基丁酸，BHB）的含量可作为奶牛亚临床酮症的指标。还已经证明，奶牛的牛奶中BHB浓度与酮症有很强的相关性。最近，中红外光谱（MIR）成为分析牛奶成分的一种快速，廉价且高通量的方法。这项研究的目的是对MIR预测的牛奶BHB进行全基因组关联研究（GWAS），以鉴定可能影响北美荷斯坦奶牛亚临床酮症的基因组区域，基因和途径。结果在荷斯坦奶牛的第一次泌乳（SCK1）和第二次和以后泌乳（SCK2）中，确定了几个与MIR预测的牛奶BHB浓度（亚临床酮症指标）相关的重要区域。最强的关联位于SCK1的BTA6和SCK2的BTA14。在先前报道的分别与泽西岛和荷斯坦奶牛对酮症和临床乳腺炎的易感性相关的区域和变体中，发现了BTA6上的几个SNP。在DGAT1基因中发现了BTA14上的一个非常重要的SNP，该基因对奶牛的脂肪代谢和炎症反应具有已知功能。发现BTA6上的一个区域和BTA20上的三个SNP在SCK1和SCK2之间重叠。但是，在BTA20（55-63 Mb）上还发现了一个SCK2的新区域，以前的关联研究中未对此进行报道。对MIR预测的牛奶BHB浓度在鉴定区域内的候选基因列表进行的富集分析产生了可能与奶牛的炎症反应和脂质代谢有关的分子功能和生物学过程。结论这项研究的结果证实了先前研究中确定的与酮症易感性和免疫反应有关的几个SNP和基因，还发现了一个可用于进一步分析以确定影响临床/亚临床的因果变异和关键调控基因的新区域。酮症。对MIR预测的牛奶BHB浓度在鉴定区域内的候选基因列表进行的富集分析产生了可能与奶牛的炎症反应和脂质代谢有关的分子功能和生物学过程。结论这项研究的结果证实了先前研究中确定的与酮症易感性和免疫反应有关的几个SNP和基因，还发现了一个可用于进一步分析以确定影响临床/亚临床的因果变异和关键调控基因的新区域。酮症。对MIR预测的牛奶BHB浓度在鉴定区域内的候选基因列表进行的富集分析产生了可能与奶牛的炎症反应和脂质代谢有关的分子功能和生物学过程。结论这项研究的结果证实了先前研究中确定的与酮症易感性和免疫反应有关的几个SNP和基因，还发现了一个可用于进一步分析以确定影响临床/亚临床的因果变异和关键调控基因的新区域。酮症。