Marek’s disease (MD) is a highly neoplastic disease primarily affecting chickens, and remains as a chronic infectious disease that threatens the poultry industry. Copy number variation (CNV) has been examined in many species and is recognized as a major source of genetic variation that directly contributes to phenotypic variation such as resistance to infectious diseases. Two highly inbred chicken lines, 63 (MD-resistant) and 72 (MD-susceptible), as well as their F1 generation and six recombinant congenic strains (RCSs) with varied susceptibility to MD, are considered as ideal models to identify the complex mechanisms of genetic and molecular resistance to MD. In the present study, to unravel the potential genetic mechanisms underlying resistance to MD, we performed a genome-wide CNV detection using next generation sequencing on the inbred chicken lines with the assistance of CNVnator. As a result, a total of 1649 CNV regions (CNVRs) were successfully identified after merging all the nine datasets, of which 90 CNVRs were overlapped across all the chicken lines. Within these shared regions, 1360 harbored genes were identified. In addition, 55 and 44 CNVRs with 62 and 57 harbored genes were specifically identified in line 63 and 72, respectively. Bioinformatics analysis showed that the nearby genes were significantly enriched in 36 GO terms and 6 KEGG pathways including JAK/STAT signaling pathway. Ten CNVRs (nine deletions and one duplication) involved in 10 disease-related genes were selected for validation by using quantitative real-time PCR (qPCR), all of which were successfully confirmed. Finally, qPCR was also used to validate two deletion events in line 72 that were definitely normal in line 63. One high-confidence gene, IRF2 was identified as the most promising candidate gene underlying resistance and susceptibility to MD in view of its function and overlaps with data from previous study. Our findings provide valuable insights for understanding the genetic mechanism of resistance to MD and the identified gene and pathway could be considered as the subject of further functional characterization.

中文翻译：

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使用下一代测序技术对马立克氏病的遗传抗性对宿主基因组中拷贝数变异进行全基因组表征。

马立克氏病（Marek's disease，MD）是一种高度致瘤性疾病，主要影响鸡只，并且仍是威胁禽业的慢性传染病。拷贝数变异（CNV）已在许多物种中进行了检查，被认为是直接导致表型变异（例如对传染病抗性）的遗传变异的主要来源。两种高度近交的鸡品系，分别是63（耐MD）和72（耐MD），以及它们的F1代和六种对MD易感性高的重组同系菌株（RCS），被认为是鉴定复杂机制的理想模型对MD的遗传和分子抗性 在本研究中，为了揭示潜在的遗传机制对MD的抵抗力，我们在CNVnator的协助下，对近亲鸡品系进行了下一代测序，从而进行了全基因组CNV检测。结果，合并所有九个数据集后，成功识别出总共1649个CNV区域（CNVR），其中90个CNVR重叠在所有鸡系中。在这些共享区域内，鉴定出了1360个带有窝藏的基因。另外，分别在第63和72行中特异性鉴定了55个和44个带有62和57个携带基因的CNVR。生物信息学分析表明，附近的基因在36个GO项和6个KEGG通路（包括JAK / STAT信号通路）中显着富集。通过使用定量实时PCR（qPCR）选择涉及10个与疾病相关的基因的10个CNVR（9个缺失和1个重复）进行验证，所有这些均被成功确认。最后，qPCR还用于验证第72行中的两个删除事件，这些事件在第63行中绝对是正常的。鉴于其功能和重叠情况，一种高信度基因IRF2被确定为最有希望的候选基因，其潜在耐药性和对MD的易感性从以前的研究数据。我们的发现为理解抗药性的遗传机制提供了宝贵的见识，并且所鉴定的基因和途径可被视为进一步功能表征的主题。