Badia-Bringué Gerard, Asselstine Victoria, Cánovas Ángela, Alonso-Hearn Marta
Department of Animal Health, NEIKER-Basque Institute of Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), Derio, Spain.
Department of Animal Biosciences, Center for Genetic Improvement of Livestock, University of Guelph, Guelph, ON, Canada.
Front Vet Sci. 2025 Jun 5;12:1601267. doi: 10.3389/fvets.2025.1601267. eCollection 2025.
Bovine paratuberculosis (PTB) is a chronic enteritis caused by subsp. (MAP), which results in significant economic losses to the dairy industry worldwide. Long non-coding RNAs (lncRNAs) play a crucial role in regulating the host immune response due to their interaction with transcripts in proximity. However, their annotation in cattle remains limited, and their role in cattle naturally infected with MAP has not been fully explored. In this study, lncRNAs were identified in the transcriptome of ileocecal valve samples from control cows without lesions ( = 4) and with PTB-associated focal ( = 5) and diffuse ( = 5) lesions in intestinal tissues using RNA sequencing. The raw reads were uploaded into the CLC Bio Genomics Workbench, and the trimmed reads were mapped to the ARS_UCD1.2.109 reference genome using the Large Gap Read Mapping tool. The resulting annotation allowed the identification of 1,434 LncRNAs, 899 of which were novel, using the FlExible Extraction of LncRNA pipeline. LncRNA differential expression (DE) analysis performed with allowed the identification of 1, 6, and 2 DE lncRNAs in the comparisons of cows with focal lesions () controls, diffuse lesions controls, and diffuse focal lesions, respectively. Best lncRNA partner analysis identified expression correlations between the , lncRNA , and , and the (), and the (), respectively. The negatively regulates apoptosis, the positively regulates IL-6 expression, and the regulates cell differentiation and inflammation. The results of the quantitative trait locus (QTL) enrichment analysis showed that the DE lncRNAs were located in genomic regions previously associated with clinical mastitis, HDL cholesterol, bovine tuberculosis, paratuberculosis, and bovine leukosis susceptibility. The identified DE lncRNAs could allow the development of novel PTB diagnostic tools and have potential applications in breeding strategies for PTB-resistant cattle.
牛副结核病（PTB）是由副结核分枝杆菌亚种（MAP）引起的一种慢性肠炎，给全球乳制品行业造成了重大经济损失。长链非编码RNA（lncRNAs）由于与附近的转录本相互作用，在调节宿主免疫反应中发挥着关键作用。然而，它们在牛中的注释仍然有限，其在自然感染MAP的牛中的作用尚未得到充分探索。在本研究中，使用RNA测序在无病变对照奶牛（n = 4）以及肠道组织中有PTB相关局灶性病变（n = 5）和弥漫性病变（n = 5）的回盲瓣样本转录组中鉴定lncRNAs。原始读数上传到CLC Bio基因组工作台，使用大间隙读数映射工具将修剪后的读数映射到ARS_UCD1.2.109参考基因组。使用lncRNA灵活提取管道进行的注释鉴定出1434个lncRNAs，其中899个是新的。使用该软件进行的lncRNA差异表达（DE）分析分别在局灶性病变奶牛与对照、弥漫性病变奶牛与对照以及弥漫性病变与局灶性病变的比较中鉴定出1、6和2个DE lncRNAs。最佳lncRNA伴侣分析分别确定了lncRNA与、与以及与之间的表达相关性。负向调节细胞凋亡，正向调节IL-6表达，调节细胞分化和炎症。数量性状位点（QTL）富集分析结果表明，DE lncRNAs位于先前与临床乳腺炎、高密度脂蛋白胆固醇、牛结核病、副结核病和牛白血病易感性相关的基因组区域。鉴定出的DE lncRNAs可用于开发新型PTB诊断工具，并在抗PTB牛的育种策略中具有潜在应用。
