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

传染病及其对生长性能和产量的相关影响是加拿大养猪业的一个重大经济问题。 这是一个多因素的问题，有各种遗传和环境的影响。目前，很少有遗传标记来帮助选择更好的抗病性和生长性能。在猪群中，表现不佳的猪可能在一种或多种与先天抗病性有关的基本肝脏蛋白中携带遗传缺陷，这些可能对复杂的多基因生产性状产生负面影响。我们正在采取功能基因组学方法来发现干扰先天免疫因素的基因缺陷，这些因素可能会限制健康和生产。以前，我们已经发现了疾病相关的单核苷酸多态性（SNP）损害肝脏中产生的先天免疫蛋白的结构，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参与猪先天免疫的基因的肝脏表达水平。对目标基因的启动子区进行测序，并检查是否存在与表达改变相关的SNP。 将使用来自猪的新的和存档的DNA样本（可获得辅助诊断和/或性能信息）研究已鉴定的基因缺陷（SNP）对常见传染病的先天性疾病抗性和生长性能改变的影响。 这将允许创建SNP小组，该小组将在大量具有详细健康和生产数据的猪上运行，以确定选择增加先天性疾病抗性对整体生产的影响。 最终，任何被证明有价值的SNP都将被纳入遗传选择策略，这将提高整体产量，改善猪的福利，提高生长性能，减少抗生素在猪生产中的使用，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.