Persichilli C, Biffani S, Senczuk G, Di Civita M, Bitew M K, Bosco A, Rinaldi L, Grande S, Cringoli G, Pilla F
University of Molise, Department of Agricultural, Environmental and Food Science, Campobasso, Italy.
National Council of Research, Institute for Agriculture Biology and Biotechnology, Milan, Italy.
Animal. 2025 Feb;19(2):101403. doi: 10.1016/j.animal.2024.101403. Epub 2024 Dec 19.
In sheep, gastrointestinal nematodes (GINs) can cause disease, reduced feed intake, and nutritional deficiencies. To counteract GINs, anthelmintics are widely used although it is well known they may enter the environment impacting ecosystems. In addition, anthelmintics resistance has rapidly developed and consequently, alternative approaches are crucial for profitable and sustainable sheep production. The occurrence of resistant individuals is mainly due to their intrinsic genetic diversity; therefore, the implementation of breeding plans for resistant animals may provide a promising strategy to reduce the use of anthelmintics. This study is aimed at identifying genomic regions involved in sheep resistance to GINs. To do this, faecal samples were collected from 642 Comisana and 323 Massese sheep over 3 years to assess Faecal Egg Counts, and Estimated Breeding Values (EBVs) for GIN resistance were estimated by a repeatability animal model. Then, EBVs in the 99.95th and 0.05th percentiles were used to identify the most and least "genetically resistant" individuals to GINs, using genotyped individuals with the Illumina OvineSNP50 beadchip. A genome-wide case-control analysis was performed retaining the most significant single nucleotide polymorphisms (SNPs) with a threshold of 0.005% for the false discovery rate. Genes and Quantitative Trait Loci overlapping significant SNPs were annotated and enriched respectively while genes have been also enriched for functional pathways. As a result, 13 genes on 12 chromosomes and 10 genes on 11 different chromosomes were identified in the Comisana and Massese breed, respectively. Among these, genes involved in the physiology or pathology of the gastrointestinal tract, in adaptive processes and in production traits, were detected. The enrichment analysis highlighted 36 significant pathways in the Comisana breed and 21 in the Massese breed. Many of these pathways were involved in the regulation of the immune response, drug metabolism and detoxification, and vitamin metabolism. Interestingly, pathways involved in vitamin and drug metabolism were also identified in previous research and have shown to play an active role in GIN resistance. In this study, we took advantage of the use of EBVs as a metric for GIN resistance in a case-control genome-wide framework and successfully identified several genomic regions that might be involved in the trait. The presence of overlapping functional pathways related to different genes in the two breeds seems to reinforce the idea of the polygenicity of this trait, and further studies are needed in order to make selection schemes an effective tool to contrast GINs.
在绵羊中，胃肠道线虫（GINs）可引发疾病、降低采食量并导致营养缺乏。为对抗GINs，驱虫药被广泛使用，尽管众所周知它们可能进入环境并影响生态系统。此外，驱虫药耐药性迅速发展，因此，替代方法对于盈利且可持续的绵羊生产至关重要。耐药个体的出现主要归因于其内在的遗传多样性；因此，实施针对耐药动物的育种计划可能为减少驱虫药的使用提供一个有前景的策略。本研究旨在识别与绵羊对GINs耐药性相关的基因组区域。为此，在3年时间里从642只科米萨纳绵羊和323只马塞塞绵羊中采集粪便样本以评估粪蛋计数，并通过重复性动物模型估计GINs耐药性的估计育种值（EBVs）。然后，使用Illumina OvineSNP50芯片对个体进行基因分型，将EBVs处于第99.95百分位数和第0.05百分位数的个体分别用于识别对GINs“遗传抗性”最强和最弱的个体。进行全基因组病例对照分析，保留错误发现率阈值为0.005%的最显著单核苷酸多态性（SNPs）。对与显著SNPs重叠的基因和数量性状位点分别进行注释和富集，同时也对基因的功能途径进行了富集。结果，在科米萨纳品种和马塞塞品种中分别在12条染色体上鉴定出13个基因和在11条不同染色体上鉴定出10个基因。其中，检测到了参与胃肠道生理或病理、适应性过程及生产性状的基因。富集分析突出了科米萨纳品种中的36条显著途径和马塞塞品种中的21条显著途径。这些途径中有许多参与免疫反应调节、药物代谢与解毒以及维生素代谢。有趣的是，维生素和药物代谢相关途径在先前研究中也已被识别，并且已表明在GINs耐药性中发挥积极作用。在本研究中，我们利用EBVs作为全基因组病例对照框架中GINs耐药性的衡量指标，并成功识别出了几个可能与该性状相关的基因组区域。两个品种中与不同基因相关的重叠功能途径的存在似乎强化了该性状多基因性的观点，为使选择方案成为对抗GINs的有效工具，还需要进一步研究。
