Centre for Genetic Improvement of Livestock, Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
Genomics. 2010 Mar;95(3):176-82. doi: 10.1016/j.ygeno.2010.01.001. Epub 2010 Jan 7.
Bovine Johne's disease (JD), caused by Mycobacterium avium spp. paratuberculosis (MAP), causes significant losses to the dairy and beef cattle industries. Effective vaccination or therapeutic strategies against this disease are currently unavailable and infected animals either get culled or die due to clinical disease. An alternative strategy to manage the disease is to selectively breed animals with enhanced resistance to MAP infection. Therefore, the objective of this study was to identify genetic loci putatively associated with MAP infection in a resource population consisting of Holstein cattle using a genome-wide association approach. The BovineSNP50 BeadChip, containing 54,001 single nucleotide polymorphisms (SNPs), was used to genotype 232 animals with known MAP infection status. Since, traditional case-control analytical techniques are based on single-marker analysis and do not account for the existence of linkage disequilibrium (LD) between markers, we used a novel principal component regression approach, where each SNP was fit in a logistic regression model, along with principal components of other SNPs on the same chromosome showing association with the trait, as covariates. Such an approach allowed us to account for the LD that exists between multiple markers showing an association on the same chromosome. Our analysis revealed the presence of at least 12 genomic regions on BTA1, 5, 6, 7, 10, 11 and 14 that were associated with the MAP infection status of our resource population. A brief description of these genomic regions, and a discussion of the analysis used in this study, have been presented.
牛型约翰氏病(JD)由分枝杆菌副结核亚种(MAP)引起,给奶牛和肉牛行业造成了重大损失。目前尚无针对该疾病的有效疫苗或治疗策略,受感染的动物要么被扑杀,要么因临床疾病而死亡。管理该疾病的替代策略是选择性繁殖对 MAP 感染具有增强抗性的动物。因此,本研究的目的是使用全基因组关联方法在由荷斯坦奶牛组成的资源群体中鉴定与 MAP 感染相关的遗传基因座。BovineSNP50 BeadChip 包含 54,001 个单核苷酸多态性(SNP),用于对 232 只具有已知 MAP 感染状况的动物进行基因分型。由于传统的病例对照分析技术基于单标记分析,并且不考虑标记之间存在的连锁不平衡(LD),因此我们使用了一种新的主成分回归方法,其中每个 SNP 都在逻辑回归模型中拟合,同时还拟合了与性状相关的同一染色体上其他 SNP 的主成分作为协变量。这种方法允许我们考虑到同一染色体上显示关联的多个标记之间存在的 LD。我们的分析显示,在 BTA1、5、6、7、10、11 和 14 上至少存在 12 个基因组区域与我们资源群体的 MAP 感染状况相关。简要描述了这些基因组区域,并讨论了本研究中使用的分析方法。