Kiser J N, Neupane M, White S N, Neibergs H L
Department of Animal Sciences, Washington State University, Pullman, WA, 99164, USA.
USDA-ARS Animal Disease Research Unit, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, 99164, USA.
Mamm Genome. 2018 Aug;29(7-8):539-549. doi: 10.1007/s00335-017-9725-4. Epub 2017 Nov 28.
Multiple genome-wide association analyses have investigated susceptibility to bovine paratuberculosis, but few loci have been identified across independent cattle populations. A SNP-based gene set enrichment analysis (GSEA-SNP) allows expanded identification of genes with moderate effects on a trait through the enrichment of gene sets instead of identifying only few loci with large effects. Therefore, the objective of this study was to identify genes that were moderately associated with Mycobacterium avium ssp. paratuberculosis (Map) tissue infection using GSEA-SNP in Holstein cattle from the Pacific Northwest (PNW; n = 205) and from the PNW and Northeast (PNW+NE; n = 245) which were previously genotyped with the Illumina BovineSNP50 BeadChip. The GSEA-SNP utilized 4389 gene sets from five databases. For each annotated gene in the UMD3.1 assembly (n = 19,723), the most significant SNP within each gene and its surrounding region (10 kb up- and downstream) was selected as a proxy for that gene. Any gene set with a normalized enrichment score > 2.5 was considered enriched. Thirteen gene sets (8 PNW GSEA-SNP; 5 PNW+NE) were enriched in these analyses and all have functions that relate to nuclear factor kappa beta. Nuclear factor kappa beta is critical to gut immune responses, implicated in host immune responses to other mycobacterial diseases, and has established roles in inflammation as well as cancer. Gene sets and genes moderately associated with Map infection could be used in genomic selection to allow producers to select for less susceptible cattle, lower the prevalence of the disease, and reduce economic losses.
多项全基因组关联分析已对牛副结核病的易感性进行了研究，但在独立的牛群中仅鉴定出了少数几个基因座。基于单核苷酸多态性（SNP）的基因集富集分析（GSEA-SNP）能够通过基因集的富集来扩大对性状具有中等效应的基因的鉴定，而不是仅识别少数具有大效应的基因座。因此，本研究的目的是使用GSEA-SNP在来自太平洋西北地区（PNW；n = 205）以及来自PNW和东北地区（PNW+NE；n = 245）的荷斯坦奶牛中鉴定与鸟分枝杆菌副结核亚种（Map）组织感染中度相关的基因，这些奶牛先前已使用Illumina BovineSNP50 BeadChip进行了基因分型。GSEA-SNP利用了来自五个数据库的4389个基因集。对于UMD3.1组装中的每个注释基因（n = 19,723），选择每个基因及其周围区域（上下游各10 kb）内最显著的SNP作为该基因的代表。任何标准化富集分数> 2.5的基因集都被视为富集。在这些分析中，有13个基因集（8个PNW GSEA-SNP；5个PNW+NE）被富集，并且所有基因集都具有与核因子κB相关的功能。核因子κB对肠道免疫反应至关重要，与宿主对其他分枝杆菌疾病的免疫反应有关，并且在炎症和癌症中已确立了作用。与Map感染中度相关的基因集和基因可用于基因组选择，以使生产者能够选择易感性较低的牛，降低疾病的流行率，并减少经济损失。
