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Identification of potential functional variants underlying ovine resistance to gastrointestinal nematode infection by using RNA‐Seq
Animal Genetics ( IF 2.4 ) Pub Date : 2020-01-03 , DOI: 10.1111/age.12894
P K Chitneedi 1 , J J Arranz 1 , A Suárez-Vega 1 , M Martínez-Valladares 2, 3 , B Gutiérrez-Gil 1
Affiliation  

In dairy sheep flocks from Mediterranean countries, replacement and adult ewes are the animals most affected by gastrointestinal nematode (GIN) infections. In this study, we have exploited the information derived from an RNA‐Seq experiment with the aim of identifying potential causal mutations related to GIN resistance in sheep. Considering the RNA‐Seq samples from 12 ewes previously classified as six resistant and six susceptible animals to experimental infection by Teladorsagia circumcincta, we performed a variant calling analysis pipeline using two different types of software, gatk version 3.7 and Samtools version 1.4. The variants commonly identified by the two packages (high‐quality variants) within two types of target regions – (i) QTL regions previously reported in sheep for parasite resistance based on SNP‐chip or sequencing technology studies and (ii) functional candidate genes selected from gene expression studies related to GIN resistance in sheep – were further characterised to identify mutations with a potential functional impact. Among the genes harbouring these potential functional variants (930 and 553 respectively for the two types of regions), we identified 111 immune‐related genes in the QTL regions and 132 immune‐related genes from the initially selected candidate genes. For these immune‐related genes harbouring potential functional variants, the enrichment analyses performed highlighted significant GO terms related to apoptosis, adhesion and inflammatory response, in relation to the QTL related variants, and significant disease‐related terms such as inflammation, adhesion and necrosis, in relation to the initial candidate gene list. Overall, the study provides a valuable list of potential causal mutations that could be considered as candidate causal mutations in relation to GIN resistance in sheep. Future studies should assess the role of these suggested mutations with the aim of identifying genetic markers that could be directly implemented in sheep breeding programmes considering not only production traits, but also functional traits such as resistance to GIN infections.

中文翻译:

使用RNA‐Seq识别绵羊对胃肠道线虫感染的潜在潜在功能变异

在来自地中海国家的奶牛羊群中,代母羊和成年母羊是受胃肠道线虫(GIN)感染影响最大的动物。在这项研究中,我们利用了来自RNA-Seq实验的信息,目的是鉴定与绵羊GIN抗性相关的潜在因果突变。考虑到来自12头母羊的RNA-Seq样本先前被分为六种抗性和六种易感动物,受到实验性圆环Teladorsagia circumcincta的感染,我们使用两种不同类型的软件(gatk 3.7版和Samtools)执行了变异调用分析流程版本1.4。通常在两种类型的目标区域内由两种包装识别的变异(高质量变异)–(i)先前根据SNP芯片或测序技术研究在绵羊中报告的寄生虫抗性QTL区域,以及(ii)选择的功能候选基因来自与绵羊GIN抗性相关的基因表达研究的结果–进一步表征以鉴定具有潜在功能影响的突变。在具有这些潜在功能变异的基因中(两种类型的区域分别为930和553),我们从最初选择的候选基因中鉴定出QTL区域中的111个免疫相关基因和132个免疫相关基因。对于这些具有潜在功能变异的免疫相关基因,进行的富集分析突出了与凋亡相关的重要GO术语,与QTL相关变体有关的黏附和炎症反应,以及与初始候选基因列表有关的与疾病相关的重要术语,例如炎症,黏附和坏死。总体而言,该研究提供了有价值的潜在因果突变列表,这些潜在因果突变可被视为与绵羊GIN抗性相关的候选因果突变。未来的研究应评估这些建议的突变的作用,以鉴定可以直接在绵羊育种计划中实施的遗传标记,不仅要考虑生产性状,还要考虑功能性状如对GIN感染的抵抗力。关于初始候选基因列表。总体而言,该研究提供了有价值的潜在因果突变列表,这些潜在因果突变可被视为与绵羊GIN抗性相关的候选因果突变。未来的研究应评估这些建议的突变的作用,以鉴定可以直接在绵羊育种计划中实施的遗传标记,不仅要考虑生产性状,还要考虑功能性状如对GIN感染的抵抗力。关于初始候选基因列表。总体而言,该研究提供了有价值的潜在因果突变列表,这些潜在因果突变可被视为与绵羊GIN抗性相关的候选因果突变。未来的研究应评估这些建议的突变的作用,以鉴定可以直接在绵羊育种计划中实施的遗传标记,不仅要考虑生产性状,还要考虑功能性状如对GIN感染的抵抗力。
更新日期:2020-04-21
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