Genes controlling vaccine responses and disease resistance to respiratory viral pathogens in cattle.

Genes controlling vaccine responses and disease resistance to respiratory viral pathogens in cattle.
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DOI:
10.1016/j.vetimm.2011.05.009
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发表时间:
2012-07-15
影响因子:
1.8
通讯作者:
Jann OC
Jann OC
中科院分区:
农林科学3区
文献类型:
--
作者:
Glass EJ;Baxter R;Leach RJ;Jann OC

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农场动物仍然面临地方性、外来和新出现病毒的风险。疫苗接种通常被认为是最好的解决方案,但对于许多病原体来说,要么没有合适的疫苗,要么现有的疫苗远非理想。疾病控制的一种补充方法可能是鉴定在疾病抗性和对疫苗接种的反应中的遗传变异基础的基因和染色体区域。然而,因果多态性的鉴定并不简单,因为它通常需要大量具有连锁表型和基因型的动物。研究复杂性状(如对病毒病原体的抗性或反应)的基因需要几种遗传学方法,包括从导致保护或病理的细胞途径的知识中推导出的候选基因,或使用分布在基因组中的标记进行无偏倚的全基因组扫描。牛中的许多病毒性疾病存在宿主遗传变异的证据,包括牛呼吸道疾病和传闻中的口蹄疫病毒(FMDV)。我们用来自口蹄疫病毒的40聚体肽和牛呼吸道合胞病毒(BRSV)疫苗对牛杂交群进行免疫接种。遗传变异已经量化。候选基因的方法分组高和低抗体和T细胞反应的共同基序的肽结合口袋的牛主要组织相容性复合体(BoLA)DRB 3基因。这表明可以设计具有最少数量的被大多数牛识别的表位的疫苗。利用微卫星和单核苷酸多态性(SNP)标记进行的全基因组扫描揭示了许多新的控制体液和细胞介导免疫的数量性状位点(QTL)和SNP标记,其中一些位于已知免疫相关性的基因中,包括Toll样受体(TLR)。家畜基因组的测序、组装和注释正在快速进行。此外,高密度SNP芯片的提供应该使得有可能在田间群体中将表型与基因型联系起来,而不需要结构化群体或系谱信息。这将有望实现QTL的精细定位和致病基因的最终鉴定。这项研究可能会导致选择对疾病更具抵抗力的动物和提高疫苗效力的新方法。
Farm animals remain at risk of endemic, exotic and newly emerging viruses. Vaccination is often promoted as the best possible solution, and yet for many pathogens, either there are no appropriate vaccines or those that are available are far from ideal. A complementary approach to disease control may be to identify genes and chromosomal regions that underlie genetic variation in disease resistance and response to vaccination. However, identification of the causal polymorphisms is not straightforward as it generally requires large numbers of animals with linked phenotypes and genotypes. Investigation of genes underlying complex traits such as resistance or response to viral pathogens requires several genetic approaches including candidate genes deduced from knowledge about the cellular pathways leading to protection or pathology, or unbiased whole genome scans using markers spread across the genome. Evidence for host genetic variation exists for a number of viral diseases in cattle including bovine respiratory disease and anecdotally, foot and mouth disease virus (FMDV). We immunised and vaccinated a cattle cross herd with a 40-mer peptide derived from FMDV and a vaccine against bovine respiratory syncytial virus (BRSV). Genetic variation has been quantified. A candidate gene approach has grouped high and low antibody and T cell responders by common motifs in the peptide binding pockets of the bovine major histocompatibility complex (BoLA) DRB3 gene. This suggests that vaccines with a minimal number of epitopes that are recognised by most cattle could be designed. Whole genome scans using microsatellite and single nucleotide polymorphism (SNP) markers has revealed many novel quantitative trait loci (QTL) and SNP markers controlling both humoral and cell-mediated immunity, some of which are in genes of known immunological relevance including the toll-like receptors (TLRs). The sequencing, assembly and annotation of livestock genomes and is continuing apace. In addition, provision of high-density SNP chips should make it possible to link phenotypes with genotypes in field populations without the need for structured populations or pedigree information. This will hopefully enable fine mapping of QTL and ultimate identification of the causal gene(s). The research could lead to selection of animals that are more resistant to disease and new ways to improve vaccine efficacy.
DOI: 10.1371/journal.pone.0008940
发表时间: 2010-01-28
期刊: PloS one
影响因子: 3.7
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DOI: 10.4049/jimmunol.165.1.134
发表时间: 2000-07-01
影响因子: 4.4
作者:
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DOI: 10.1016/j.vaccine.2009.09.131
发表时间: 2009-12-10
期刊: VACCINE
影响因子: 5.5
作者:
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通讯作者: Glass, E. J.