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Genetic variation in candidate inflammatory-related genes and its relation to infectious bovine disease.

机译:候选炎症相关基因的遗传变异及其与牛传染病的关系。

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摘要

Infectious disease can have a considerable impact on the dairy' industry worldwide. Breeding livestock for disease resistance has been long sought as a means to reduce such impact; unfortunately, this approach has traditionally yielded little genetic gain. However, recent advances in genomic technologies teamed with an approach known as marker-assisted selection, have the potential to make these breeding goals a reality.;The use of genetic markers in a selective breeding program focusing to improve disease resistance will likely be of great importance in the near future. The current research emphasizes that it is necessary to functionally validate resultant genetic associations as they could be due to linkage disequilibrium with the true causal polymorphism. Furthermore, it has provided compelling evidence that SNPs in IL10RA and MIF should be considered as worthwhile candidates to reduce the susceptibility of dairy cattle to mastitis or Johne's disease.;The purpose of this study was to identify single nucleotide polymorphisms (SNPs), which are associated with the susceptibility of dairy cattle to mastitis and Johne's disease. The candidate genes interleukin-10 (IL10) and its receptor (IL10RA/B), transforming growth factor beta 1 (TGFB1) and its receptor (TGFBR1/1), macrophage migration inhibitory factor (MIF), and natural resistance-associated macrophage protein 1 (NRAMP1), were selected for SNP discovery based on their importance in modulating the innate inflammatory response to bacteria. Sixteen SNPs were identified in IL10 (n=2), IL10RA/B (n=6/2), TGFB1 (n=1), MIF (n=3) and NRAMP1 (n=2), which were subsequently genotyped in a sample population of Holstein bulls and cows. Genetic association analysis identified significant effects for SNPs in IL10RA with estimated breeding values for somatic cell score (SCS), an indicator trait for mastitis, and for SNPs in IL10RA and MIF with Mycobacterium avium ssp. paratuberculosis (MAP) infection status, an indicator trait for Johne's disease. Functional validation of SNPs in MIF using a dual luciferase reporter gene assay supported the observed genetic associations. Finally, comparison of gene expression profiles of peripheral blood mononuclear cells in healthy and MAP-infected Holstein and Jersey cows identified novel breed-specific differences as well as new candidates for future genetic association studies.
机译:传染病会对全球乳业产生重大影响。长期以来,人们一直在寻求牲畜的抗病育种,以减少这种影响。不幸的是,这种方法传统上很少产生遗传增益。然而,基因组技术的最新进展与标记辅助选择方法相结合,有可能实现这些育种目标。在专注于提高抗病性的选择性育种计划中使用遗传标记可能具有很大的意义。在不久的将来的重要性。当前的研究强调,必须在功能上验证所得的遗传关联,因为它们可能是由于连锁不平衡与真正的因果多态性引起的。此外,它提供了令人信服的证据,应认为IL10RA和MIF中的SNPs可以作为降低奶牛对乳腺炎或Johne's疾病敏感性的有价值的候选对象。本研究的目的是鉴定单核苷酸多态性(SNPs),与奶牛对乳腺炎和约翰氏病的易感性有关。候选基因白介素10(IL10)及其受体(IL10RA / B),转化生长因子β1(TGFB1)及其受体(TGFBR1 / 1),巨噬细胞迁移抑制因子(MIF)和与自然抗性相关的巨噬细胞蛋白根据其在调节细菌固有发炎反应中的重要性,选择了1个(NRAMP1)用于SNP发现。在IL10(n = 2),IL10RA / B(n = 6/2),TGFB1(n = 1),MIF(n = 3)和NRAMP1(n = 2)中鉴定了16个SNP,随后将它们分型。荷斯坦公牛和奶牛的样本种群。遗传关联分析确定了IL10RA中SNP的显着影响,其体细胞评分(SCS)的估计育种值为乳腺炎的指示性状,禽类分枝杆菌ssp对IL10RA和MIF中的SNP具有明显的育种价值。副结核病(MAP)感染状况,这是约翰德氏病的一种指示性特征。使用双重萤光素酶报告基因分析对MIF中SNP进行功能验证,支持了所观察到的遗传关联。最后,通过比较健康的和MAP感染的荷斯坦奶牛和泽西奶牛外周血单核细胞的基因表达谱,发现了新的品种特异性差异以及未来遗传关联研究的新候选者。

著录项

  • 作者

    Verschoor, Chris Peter.;

  • 作者单位

    University of Guelph (Canada).;

  • 授予单位 University of Guelph (Canada).;
  • 学科 Biology Genetics.;Agriculture Animal Pathology.;Agriculture Animal Culture and Nutrition.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 148 p.
  • 总页数 148
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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