Strillacci Maria G, Ferrulli Vincenzo, Bernini Francesca, Pravettoni Davide, Bagnato Alessandro, Martucci Ilaria, Boccardo Antonio
Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, Via dell'Università 6, Lodi, Italy.
PLoS One. 2025 Mar 21;20(3):e0318520. doi: 10.1371/journal.pone.0318520. eCollection 2025.
Bovine respiratory disease (BRD) poses a significant risk of morbidity and mortality in preweaned dairy calves. Research indicates that this multifactorial disorder can be attributed to the involvement of various pathogens. Currently, there is little information from genome-wide association studies (GWAS) for BRD resistance in young calves based on objective measures and classification of the disease. In this study, we moved forward in phenotyping BRD by coupling two diagnostic tests, the thoracic ultrasonography (TUS) and Wisconsin respiratory score (WISC), in order to assess susceptible and resistant animals to BRD. A total of 240 individuals were scored for BRD using TUS and WISC. A GWAS was performed using a selective genotyping approach to identify Quantitative Trait Loci (QTL) for BRD resistance. A total of 47 calves classified as BRD resistant (TUS ≤ 1/ WISC ≤ 4) and 47 as BRD susceptible (TUS = 5/ any WISC) were genotyped with the NEOGEN's GGP Bovine 100K SNP chip. QTL were then identified comparing the SNPs allelic frequencies between the two groups. A total of 28 QTL regions (QTLRs) were defined according to significative SNPs, 141 genes were annotated in the defined QTLRs. The genes were functionally classified into 4 main categories, i.e., i) regulation of systemic arterial blood pressure, ii) fertility, iii) immune function, and iv) filament cytoskeleton. Furthermore, 61 out of 141 genes identified here can be considered promising candidate genes since they were already associated with BRD resistance in published GWAS studies in dairy cattle. The ASB9, BMX, EPSTI1, and OLFM4 genes were identified in 4 of the 6 considered studies. This study paves the way for further research to mine the genome for resistance to respiratory diseases, utilizing an accurate classification process.
牛呼吸道疾病(BRD)对断奶前的奶牛犊构成了重大的发病和死亡风险。研究表明,这种多因素疾病可归因于多种病原体的参与。目前,基于对疾病的客观测量和分类,关于幼龄犊牛BRD抗性的全基因组关联研究(GWAS)的信息很少。在本研究中,我们通过结合两种诊断测试,即胸部超声检查(TUS)和威斯康星呼吸评分(WISC),对BRD进行表型分析,以评估对BRD易感和抗性的动物。共有240头个体通过TUS和WISC进行了BRD评分。使用选择性基因分型方法进行GWAS,以鉴定BRD抗性的数量性状位点(QTL)。共有47头被分类为BRD抗性(TUS≤1/WISC≤4)和47头BRD易感(TUS = 5/任何WISC)的犊牛用NEOGEN的GGP Bovine 100K SNP芯片进行基因分型。然后通过比较两组之间的SNP等位基因频率来鉴定QTL。根据有意义的SNP定义了总共28个QTL区域(QTLR),在定义的QTLR中注释了141个基因。这些基因在功能上分为4个主要类别,即:i)体循环动脉血压调节,ii)生育能力,iii)免疫功能,和iv)丝状细胞骨架。此外,在此鉴定的141个基因中有61个可被视为有前景的候选基因,因为它们在已发表的奶牛GWAS研究中已经与BRD抗性相关。在6项考虑的研究中有4项鉴定出了ASB9、BMX、EPSTI1和OLFM4基因。本研究为利用准确的分类过程进一步挖掘基因组中的呼吸道疾病抗性研究铺平了道路。