Genome-wide identification of genetic defects in innate disease resistance genes of swine

传染病及其对生长性能和生产的相关影响是加拿大养猪生产中的一个重大经济问题。这是一个多因素的问题，有各种遗传和环境影响。目前，几乎没有遗传标记来辅助选择以获得更好的抗病和生长性能。在一个猪群中，表现不佳的猪可能携带一种或多种与先天疾病抗性有关的基本肝脏蛋白的遗传缺陷，这些缺陷可能会对复杂的多基因生产性状产生负面影响。我们正在采用功能基因组学的方法来发现基因缺陷，这些缺陷干扰了可能限制健康和生产的先天免疫因素。以前，我们已经发现了疾病相关的单核苷酸多态(SNPs)，它损害了肝脏产生的天然免疫蛋白的结构、功能和/或表达。目前的项目将使用全基因组表达微阵列方法来识别和比较猪先天免疫相关基因的肝脏表达水平。将对感兴趣基因的启动子区域进行测序，并检查是否存在与表达变化相关的SNPs。已识别的基因缺陷(SNPs)对先天性疾病对常见传染病的抵抗力和改变的生长性能的影响将使用新的和存档的猪DNA样本进行研究，这些样本可以获得辅助诊断和/或性能信息。这将允许创建一个SNP小组，该小组将在具有详细健康和生产数据的大量猪身上运行，以确定选择提高先天疾病抵抗力对整体生产的影响。最终，任何被证明有价值的SNPs都将被纳入遗传选择策略，这些策略将改善整体产量，改善猪的福利，提高生长性能，并减少在养猪生产中使用抗生素，这将产生社会和生产效益。

Infectious diseases and their associated impact on growth performance and production are a significant economic concern in Canadian swine production. It is a multifactorial problem, with various genetic and environmental influences. Currently, there are few genetic markers to assist selection for better disease resistance and growth performance. Within a herd, poor performing pigs may carry genetic defects in one or more essential liver proteins involved in innate disease resistance, and these could contribute negatively to complex polygenic production traits. We are taking a functional genomics approach to discover gene defects that interfere with innate immune factors that could limit health and production. Previously we have found disease-associated single-nucleotide polymorphisms (SNPs) that impair structure, function and/or expression of innate immune proteins produced in the liver. The current project would use a genome-wide expression microarray approach to identify and compare levels of hepatic expression of genes involved in innate immunity in pigs. The promoter region of genes of interest will be sequenced and examined for the presence of SNPs associated with altered expression. The impact of identified gene defects (SNPs) on innate disease resistance to common infectious diseases and altered growth performance will be investigated using new and archived DNA samples from pigs for which ancillary diagnostic and/or performance information is available. This will allow the creation of a SNP panel which will be run on large numbers of pigs with detailed health and production data to determine the effect of selection for increased innate disease resistance on overall production. Ultimately any SNPs of proven value would be included in genetic selection strategies that will improve overall production, improve swine welfare, increase growth performance and decrease the use of antibiotics in swine production which will have societal and production benefits.