The Roslin Institute and Royal (Dick) School of Veterinary Studies R(D)SVS, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel.
Genes (Basel). 2020 Aug 30;11(9):1019. doi: 10.3390/genes11091019.
Marek's disease (MD) represents a significant global economic and animal welfare issue. Marek's disease virus (MDV) is a highly contagious oncogenic and highly immune-suppressive α-herpes virus, which infects chickens, causing neurological effects and tumour formation. Though partially controlled by vaccination, MD continues to have a profound impact on animal health and on the poultry industry. Genetic selection provides an alternative and complementary method to vaccination. However, even after years of study, the genetic mechanisms underlying resistance to MDV remain poorly understood. The Major Histocompatability Complex (MHC) is known to play a role in disease resistance, along with a handful of other non-MHC genes. In this study, one of the largest to date, we used a multi-facetted approach to identify QTL regions (QTLR) influencing resistance to MDV, including an F population from a full-sib advanced intercross line (FSIL) between two elite commercial layer lines differing in resistance to MDV, RNA-seq information from virus challenged chicks, and genome wide association study (GWAS) from multiple commercial lines. Candidate genomic elements residing in the QTLR were further tested for association with offspring mortality in the face of MDV challenge in eight pure lines of elite egg-layer birds. Thirty-eight QTLR were found on 19 chicken chromosomes. Candidate genes, miRNAs, lncRNAs and potentially functional mutations were identified in these regions. Association tests were carried out in 26 of the QTLR, using eight pure lines of elite egg-layer birds. Numerous candidate genomic elements were strongly associated with MD resistance. Genomic regions significantly associated with resistance to MDV were mapped and candidate genes identified. Various QTLR elements were shown to have a strong genetic association with resistance. These results provide a large number of significant targets for mitigating the effects of MDV infection on both poultry health and the economy, whether by means of selective breeding, improved vaccine design, or gene-editing technologies.
马立克氏病（MD）是一个全球性的重大经济和动物福利问题。马立克氏病病毒（MDV）是一种高度传染性的致瘤和高度免疫抑制的α疱疹病毒，可感染鸡，引起神经效应和肿瘤形成。尽管部分通过疫苗接种进行了控制，但 MD 仍然对动物健康和家禽业产生深远影响。遗传选择提供了一种替代和补充疫苗接种的方法。然而，即使经过多年的研究，对 MDV 抗性的遗传机制仍了解甚少。主要组织相容性复合体（MHC）已知在疾病抗性中发挥作用，还有少数其他非 MHC 基因。在这项迄今为止规模最大的研究中，我们使用了多方面的方法来确定影响 MDV 抗性的 QTL 区域（QTLR），包括来自两个在 MDV 抗性方面存在差异的优质商业层线之间的全同胞先进互交系（FSIL）的 F 群体、受病毒挑战的雏鸡的 RNA-seq 信息以及来自多个商业系的全基因组关联研究（GWAS）。候选基因组元素驻留在 QTLR 中，然后在面临 MDV 挑战时，在 8 个优质蛋鸡纯系中进一步测试与后代死亡率的关联。在 19 条鸡染色体上发现了 38 个 QTLR。在这些区域中鉴定出候选基因、miRNA、lncRNA 和潜在功能突变。在 26 个 QTLR 中进行了关联测试，使用 8 个优质蛋鸡纯系。许多候选基因组元素与 MD 抗性强烈相关。绘制了与 MDV 抗性显著相关的基因组区域，并鉴定了候选基因。各种 QTLR 元素被证明与抗性具有很强的遗传关联。这些结果为减轻 MDV 感染对家禽健康和经济的影响提供了大量重要的目标，无论是通过选择性育种、改进疫苗设计还是基因编辑技术。
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