A Preliminary Study of Genetic Factors That Influence Susceptibility to Bovine Tuberculosis in the British Cattle Herd
A Preliminary Study of Genetic Factors That Influence Susceptibility to Bovine Tuberculosis in the British Cattle Herd
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DOI：
10.1371/journal.pone.0018806
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发表时间：
2011-04-12
期刊：
影响因子：
3.7
通讯作者：
Amos, William
中科院分区：
文献类型：
--
作者：
Driscoll, Erin E.;Hoffman, Joseph I.;Amos, William
在一些物种中已经报道了特定宿主基因与分枝杆菌感染（如结核病）易感性之间的关联。牛结核病（bTB）对英国养牛业的影响很大，但遗传倾向尚未确定。因此，我们使用候选基因方法研究了384头牛，其中160头对抗原皮肤试验（“反应堆”）反应积极。我们的方法是不寻常的，因为它使用了微卫星标记，包含了高品种多样性，并特别关注于检测显示杂合子优势的基因，这是一种在基于snp的研究中经常被忽视的作用模式。使用一组中性标记来控制种群子结构，并使用基于一般线性模型的方法来控制年龄。我们发现亚结构出奇地弱，并鉴定了两个与反应器状态密切相关的基因组区域，通过标记INRA111和BMS2753鉴定。一般来说，检测到的关联强度倾向于根据模型中是否包含年龄而变化。在INRA111中，单一基因型表现出很强的保护作用，总体优势比为2.2，这种效果在9个不同品种中是一致的。我们的研究结果表明，可以设计出明显增加牛对bTB的遗传抗性的育种策略（严格地说，减少反应器的发生频率），这对当前关于獾扑杀的争论具有启示意义。
Associations between specific host genes and susceptibility to Mycobacterial infections such as tuberculosis have been reported in several species. Bovine tuberculosis (bTB) impacts greatly the UK cattle industry, yet genetic predispositions have yet to be identified. We therefore used a candidate gene approach to study 384 cattle of which 160 had reacted positively to an antigenic skin test ('reactors'). Our approach was unusual in that it used microsatellite markers, embraced high breed diversity and focused particularly on detecting genes showing heterozygote advantage, a mode of action often overlooked in SNP-based studies. A panel of neutral markers was used to control for population substructure and using a general linear model-based approach we were also able to control for age. We found that substructure was surprisingly weak and identified two genomic regions that were strongly associated with reactor status, identified by markers INRA111 and BMS2753. In general the strength of association detected tended to vary depending on whether age was included in the model. At INRA111 a single genotype appears strongly protective with an overall odds ratio of 2.2, the effect being consistent across nine diverse breeds. Our results suggest that breeding strategies could be devised that would appreciably increase genetic resistance of cattle to bTB (strictly, reduce the frequency of incidence of reactors) with implications for the current debate concerning badger-culling.