Genetic markers and Bovine Johne's disease

约翰氏病（JD）是一种对乳制品行业具有重大经济意义的疾病，由于其致病菌鸟分枝杆菌（Mycobacterium avium subsp.）副结核病缺乏高效疫苗和有效治疗方法阻碍了JD在全球范围内的控制。鉴于其可遗传的性质，正如各种研究所表明的那样，降低JD发病率的一种方法是在育种计划中采用遗传选择来产生具有增强抗病性的后代。为了实现这一目标，有必要确定与JD相关的遗传标记并评估其生物学相关性。在过去的十年中，许多基因组研究已经确定了与JD相关的不同遗传标记。这些研究的不一致发现表明JD是一种复杂的疾病，本质上是多基因的，有许多潜在的遗传标记影响抗病性。在将这些遗传标记用于遗传选择之前，需要在独立群体中进一步验证这些遗传标记，这是本研究的目的。具体目标是：a）验证和确认先前与加拿大荷斯坦牛群体中遗传标记和JD的关联，B）评估这些标记对生产和健康性状的潜在影响，以及c）使用转基因牛细胞系体外表征其生物学相关性。从这项研究中获得的新知识将有助于乳制品行业通过遗传选择提高对JD的抗性。

Johne's disease (JD) is a disease with great economic implications to the dairy industry and is also attractingsignificant public health concern owing to the possible zoonotic nature of its causative bacteria,Mycobacterium avium subsp. paratuberculosis. The lack of availability of vaccines with high efficacy as wellas effective treatments has hindered control of JD worldwide. Given its heritable nature, as indicated in variousstudies, one means of reducing the incidence of JD is by employing genetic selection in breeding programs toproduce offspring with enhanced disease resistance. To achieve this, it is necessary to identify genetic markersassociated with JD and to assess their biological relevance. Over the past decade, a number of genomic studieshave identified different genetic markers associated with JD. Inconsistent findings from these studies suggestthat JD is a complex disease that is polygenic in nature with many potential genetic markers influencing diseaseresistance. There is a need to further validate these genetic markers in independent populations before they canbe used in genetic selection programs, and this is the aim of the present study. The specific objectives are to: a)validate and confirm previous associations with genetic markers and JD in a Canadian Holstein population, b)assess potential impact of these markers on production and health traits, and c) characterize their biologicalrelevance in vitro using genetically modified bovine cell lines. New knowledge obtained from this study willhelp dairy industry move forward to enhance resistance to JD through genetic selection.