An integrative genomics approach to uncover genetic mechanisms underlying susceptibility to important infectious diseases in pigs

揭示猪对重要传染病易感性的遗传机制的综合基因组学方法

• 批准号: RGPIN-2016-04230
• 负责人: Stothard, Paul
• 金额: $ 2.99万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=666061
• 关键词: integrative; genomics; approach; uncover; genetic

In animal production systems infectious diseases are of great concern due to their effects on animal health and welfare, animal productivity, and in some cases human health. Variation in the ability of individuals to overcome infection has long been observed, and this variation has a genetic component, although the particular genes and genetic variants (polymorphisms) are largely unknown. Recent work has identified one of the mechanisms underlying variation in host response to infection, at least in the case of pigs and the porcine respiratory and reproductive syndrome virus (PRRSV). A polymorphism in a host gene called GBP5 affects the ability of the gene to function. Pigs with two copies of the less active version of the gene show reduced growth and higher levels of the virus. Although GBP5 has a known role in immune response in other species, its contribution to variation in viral response in pigs was previously not known. Our more recent work has revealed several additional genes that appear to differ in activity among individuals because of polymorphisms, such that certain versions of the gene (alleles) lead to greater host resistance to PRRSV. We will study the expression of these genes to learn more about what they do, and to verify the effects of polymorphisms on their activity. Next we will leverage a large existing collection of samples and phenotypic (trait) data from previous and current projects investigating Salmonella infection in pigs, to determine if these genes and polymorphisms can also provide some protection against Salmonella. Previous studies in other species suggest that this is a reasonable expectation for some genes. Indeed, in mice a link between GBP5 activity and Salmonella growth has been previously identified. The approaches we are using have the potential to identify mechanisms of pathogen resistance not previously described in pigs or other species. Moreover, the genes and polymorphisms we confirm to influence PRRSV resistance or Salmonella resistance can be used to guide the development of new non-drug based strategies for dealing with these pathogens. For example, when pigs are selected for breeding, efforts can be made to avoid individuals that carry an abundance of susceptible alleles.**

在动物生产系统中，传染病由于其对动物健康和福利、动物生产力以及在某些情况下对人类健康的影响而受到极大关注。长期以来，人们一直观察到个体克服感染的能力存在差异，这种差异具有遗传成分，尽管特定的基因和遗传变异（多态性）在很大程度上是未知的。最近的工作已经确定了宿主对感染反应的变化的潜在机制之一，至少在猪和猪呼吸与生殖综合征病毒（PRRSV）的情况下。宿主基因GBP5的多态性影响基因的功能。带有两个拷贝的活性较低的基因的猪表现出较低的生长速度和较高的病毒水平。虽然GBP5在其他物种的免疫应答中具有已知的作用，但其对猪病毒应答变异的贡献以前并不清楚。我们最近的工作揭示了几个额外的基因，由于多态性，这些基因在个体之间的活性似乎不同，因此某些版本的基因（等位基因）导致宿主对PRRSV的抗性更强。我们将研究这些基因的表达，以了解更多关于它们的作用，并验证多态性对其活性的影响。接下来，我们将利用大量现有的样本和表型（性状）数据，这些数据来自以前和目前调查猪沙门氏菌感染的项目，以确定这些基因和多态性是否也可以提供一些预防沙门氏菌的保护。 以前在其他物种中的研究表明，这是对某些基因的合理预期。事实上，在小鼠中，先前已经确定了GBP5活性与沙门氏菌生长之间的联系。我们正在使用的方法有可能确定以前在猪或其他物种中没有描述的病原体抗性机制。此外，我们确认影响PRRSV耐药性或沙门氏菌耐药性的基因和多态性可用于指导开发新的非药物治疗策略，以应对这些病原体。例如，当选择猪进行育种时，可以努力避免携带大量易感等位基因的个体。