GCRF-BBR: Beyond the genome: Enabling tropical livestock EWAS of infectious diseases

GCRF-BBR：超越基因组：实现热带牲畜传染病的 EWAS

• 批准号: BB/P024025/1
• 负责人: James Prendergast
• 金额: $ 7.69万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP024025%2F1
• 关键词: GCRF; BBR; Beyond; genome; Enabling; GCRF; BBR; Beyond; genome; Enabling

Cattle are a vital component of the economies of low and middle income countries across the globe. They are a source of meat and dairy products, provide leather and other by-products and are often used as working animals. Cattle can be grazed where crops are not easily grown, provide manure as effective fertiliser and can convert forage into high-protein food. Often cattle are the most valuable possession individuals in low and middle income countries own, but are susceptible to a range of infectious diseases, which not only inflict a heavy economic burden on these countries but can also often be transmissible to humans.Over two-thirds of the global cattle population are in low and middle income countries. Reducing the burden of cattle infectious diseases would consequently have major benefits to these areas. However for many diseases no vaccine or treatment is available. Where they are available, poor veterinary services generally mean the livestock keepers must pay for vaccines and treatments themselves. Consequently these diseases are major barriers to escaping poverty. Due to the co-evolution of pathogens and cattle there are various examples of cattle breeds that show natural tolerance or resistance to important infectious diseases. Although these breeds are often less productive, making them less attractive to LMIC farmers, if the mechanisms underlying their resistance could be identified and harnessed, then breeds of both higher productivity and tolerance could potentially be developed.The aim of this project is to develop the framework to enable the identification of genomic regions linked to tolerance/resistance via epigenome-wide association studies (EWAS). Differences in the epigenome, chemical modifications that overlay the genome, are linked to phenotypes through their association with gene regulation. By comparing the epigenomes of tolerant and susceptible animals it is possible to determine regions linked to disease resistance. However, at present we lack even baseline information on the epigenomes of LMIC cattle breeds, and the tools and resources for undertaking blood-based EWAS. In particular, as blood samples are a composite of various cell types, each with a distinct epigenome profile, it is necessary to disentangle any epigenetic alterations linked to disease tolerance from differences resulting purely from variation in cell-type composition between samples. We will address this by generating an epigenome atlas of major immune cell types across the two major sub-species of cattle prevalent in LMICs. Using this resource we will create a web portal to enable users to estimate the cell-type composition in their samples, allowing downstream EWAS not confounded by between sample composition variations, providing a greater ability to identify true epigenome differences linked to infectious diseases.

牛是全球低收入国家经济体的重要组成部分。它们是肉类和乳制品的来源，提供皮革和其他副产品，通常用作工作动物。可以在农作物不容易种植的地方放牧牛，提供有效的肥料，并可以将草料转化为高蛋白食物。通常，牛是中低收入国家拥有的最有价值的所有人，但容易受到一系列传染病的影响，不仅会给这些国家造成沉重的经济负担，而且通常也可以向人类传播。超过三分之二的全球牛群在低收入国家中。因此，减轻牛传染病的负担将对这些地区带来重大利益。但是，对于许多疾病，没有疫苗或治疗。在可用的地方，不良的兽医服务通常意味着牲畜饲养者必须自己支付疫苗和治疗费用。因此，这些疾病是逃避贫困的主要障碍。由于病原体和牛的共同进化，牛品种的各种例子表现出对重要传染病的自然耐受性或抗性。尽管这些品种的生产率通常较低，因此它们对LMIC农民的吸引力就降低了，但如果可以识别和利用其抵抗力的机制，那么可能会发展出更高的生产率和耐受性的繁殖。表观基因组的差异，覆盖基因组的化学修饰，通过与基因调节的关联与表型有关。通过比较耐受性和易感动物的表观基因组，可以确定与抗病性相关的区域。但是，目前，我们甚至缺乏有关LMIC牛品种的表观基因组的基线信息，以及用于接受血液的EWA的工具和资源。特别是，由于血液样本是各种细胞类型的复合物，每种细胞都具有独特的表观基因组谱，因此有必要将与疾病耐受性相关的任何表观遗传学改变与样品之间细胞型组成的变化所产生的差异相关的任何表观遗传学改变。我们将通过在LMIC中普遍存在的两个主要的牛主要亚种中产生一个主要免疫细胞类型的表观基因组大图。使用此资源，我们将创建一个Web门户，以使用户能够估算样品中的细胞类型组成，从而使下游ewas不会被样本组成变化之间的混淆，从而提供了更大的能力，可以识别与传染病相关的真实表观基因组差异。