Bovine paratuberculosis, or Johne’s disease (JD), is a contagious and incurable disease caused by Mycobacterium avium subsp. paratuberculosis (MAP). It has adverse effects on animal welfare and is very difficult to control, leading to serious economic consequences. An important line of defense to this disease is host genetic resistance to MAP, which, when it will be more fully understood, could be improved through selective breeding. Using a large dataset of Holstein cows (161,253 animals including 56,766 cows with ELISA serological phenotypes and 12,431 animals with genotypes), we applied a single-step single nucleotide polymorphism (SNP) best linear unbiased prediction approach to investigate the genetic determinism underlying resistance to this disease (heritability estimate and identification of relevant genomic regions) and estimated genetic trends, reliability, and relative risk factors associated with genomic predictions. Resistance to JD was moderately heritable (0.14) and 16 genomic regions were detected that accounted for at least 0.05% of the breeding values variance (GV) in resistance to JD, and were located on chromosomes 1, 3, 5, 6, 7, 19, 20, 21, 23, 25, and 27, with the highest percentage of variance explained by regions on chromosomes 23 (0.36% GV), 5 (0.22% GV), 1 (0.14% GV), and 3 (0.13% GV). When estimated for the whole chromosomes, the autosomes with the largest overall contributions were chromosomes 3 (5.3% GV), 10 (4.8%), 23 (4.7%), 1 (3.6%), 7 (3.4%), 5 (2.9%), 12 (2.5%), 11 (2.2%), and 13 (2%). We estimated a slightly favorable genetic trend in resistance to JD over the last two decades, which can be explained by a low positive genetic correlation between resistance to JD and total merit index (+ 0.06). Finally, in a validation population of 907 cows, relatively reliable genomic predictions (reliability = 0.55) were obtained, which allowed the identification of cows at high risk of infection. This study provides new insights into the genetic determinism of resistance to JD and shows that this trait can be predicted from SNP genotypes. It has led to the implementation of a single-step genomic evaluation that should rapidly become an effective tool for controlling paratuberculosis on French Holstein farms.

中文翻译：

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通过单步基因组评估对荷斯坦牛副结核病遗传抗性的新见解

牛副结核病或约内氏病 (JD) 是一种由鸟分枝杆菌亚种引起的传染性和无法治愈的疾病。副结核病（MAP）。它对动物福利有不利影响，而且很难控制，导致严重的经济后果。这种疾病的一个重要防线是宿主对 MAP 的遗传抗性，当它被更充分地了解时，可以通过选择性育种加以改进。使用荷斯坦奶牛的大型数据集（161,253 头动物，包括 56,766 头具有 ELISA 血清学表型的奶牛和 12,431 头具有基因型的动物），我们应用了单步单核苷酸多态性 (SNP) 最佳线性无偏预测方法来研究对这种疾病的抵抗力的遗传决定性（遗传力估计和相关基因组区域的鉴定），并估计遗传趋势、可靠性和相关风险因素基因组预测。JD 抗性为中度遗传（0.14），检测到 16 个基因组区域，占 JD 抗性育种值方差（GV）的至少 0.05%，位于染色体 1、3、5、6、7、 19, 20, 21, 23, 25, 和 27，23 号染色体 (0.36% GV)、5 (0.22% GV)、1 (0.14% GV) 和 3 (0.13%) 上的区域解释的方差百分比最高GV)。当估计整个染色体时，总贡献最大的常染色体是 3 号染色体（5.3% GV）、10 号（4.8%）、23 号（4.7%）、1 号（3.6%）、7 号（3.4%）、5 号（2.9%）、12 号（2.5%） )、11 (2.2%) 和 13 (2%)。我们估计在过去的二十年中，JD 抗性的遗传趋势略微有利，这可以通过 JD 抗性与总价值指数（+ 0.06）之间的低正遗传相关性来解释。最后，在 907 头奶牛的验证群体中，获得了相对可靠的基因组预测（可靠性 = 0.55），这使得识别处于高感染风险的奶牛成为可能。这项研究为 JD 抗性的遗传决定论提供了新的见解，并表明可以从 SNP 基因型预测这种性状。