Institute of Animal Breeding and Genetics, Justus Liebig University of Giessen, Ludwigstrasse 21,35390 Giessen, Germany.
Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584CM Utrecht, the Netherlands.
Animal. 2024 Oct;18(10):101329. doi: 10.1016/j.animal.2024.101329. Epub 2024 Sep 16.
The problem of copper (Cu) intoxication and deficiency continues to impact economic gains and animal welfare in sheep husbandry. This study investigated the ovine genome for regions and potential genes under selection for Cu accretion between sheep breeds. For this, we compared ovine single nucleotide polymorphism (SNP) data of three Cu-susceptible breeds with three Cu-tolerant breeds. After merging SNP data of breeds and removal of related individuals, a total of 229 sheep and 45 640 autosomal SNPs were left. Then, we selected 14 individuals per breed into two datasets (datasets 1 and 2) for analysis of selection signatures using the Fixation index, cross-population extended haplotype homozygosity and haplotype-based FLK methods. Selection regions shared by both datasets detected by at least two methods revealed regions on OAR 4, 8 and 11 containing 54 candidate genes under selection for Cu accretion. Enrichment analysis revealed that 19 gene ontologies and 1 enriched Kyoto encyclopaedia of genes and genomes pathway terms were associated with the candidate genes under selection. Genes such as TP53, TNFSF13, TNFSF12, ALOX15, ALOX12, EIF5A and PREP are associated with the regulation of Cu homeostasis, programmed cell death or inflammatory response. We also found an enrichment of arachidonate 15-lipoxygenase activity, arachidonate 12-lipoxygenase activity and ferroptosis that influence cellular inflammation and cell death. These results shed light on ovine genomic regions under selection for Cu accretion and provide information on candidate genes for further studies on breed differences in ovine Cu accretion.
铜（Cu）中毒和缺乏问题继续影响绵羊养殖的经济效益和动物福利。本研究调查了绵羊基因组中与品种间 Cu 积累相关的区域和潜在基因。为此，我们比较了三种 Cu 易感品种和三种 Cu 耐受品种的绵羊单核苷酸多态性（SNP）数据。在合并品种的 SNP 数据并去除相关个体后，总共留下了 229 只绵羊和 45640 个常染色体 SNP。然后，我们从每个品种中选择了 14 个个体分为两组（数据集 1 和 2），使用固定指数、跨群体扩展单倍型纯合度和基于单倍型的 FLK 方法分析选择特征。通过至少两种方法检测到的两个数据集共有的选择区域揭示了包含 54 个候选基因的 OAR4、8 和 11 上的选择区域，这些候选基因与 Cu 积累的选择有关。富集分析显示，19 个基因本体和 1 个富集的京都基因和基因组百科全书途径术语与选择的候选基因有关。TP53、TNFSF13、TNFSF12、ALOX15、ALOX12、EIF5A 和 PREP 等基因与 Cu 动态平衡、程序性细胞死亡或炎症反应的调节有关。我们还发现花生四烯酸 15-脂氧合酶活性、花生四烯酸 12-脂氧合酶活性和铁死亡的富集，这些都影响细胞炎症和细胞死亡。这些结果揭示了绵羊基因组中与 Cu 积累选择相关的区域，并提供了有关候选基因的信息，可为进一步研究绵羊 Cu 积累的品种差异提供信息。
