Gastroinestinal nematodes (GIN) are one of the major health problem in grazing sheep. Although genetic variability of the resistance to GIN has been documented, traditional selection is hampered by the difficulty of recording phenotypes, usually fecal egg count (FEC). To identify causative mutations or markers in linkage disequilibrium (LD) to be used for selection, the detection of quantitative trait loci (QTL) for FEC based on linkage disequilibrium-linkage analysis (LDLA) was performed on 4097 ewes (from 181 sires) all genotyped with the OvineSNP50 Beadchip. Identified QTL regions (QTLR) were imputed from whole-genome sequences of 56 target animals of the population. An association analysis and a functional annotation of imputed polymorphisms in the identified QTLR were performed to pinpoint functional variants with potential impact on candidate genes identified from ontological classification or differentially expressed in previous studies. After clustering close significant locations, ten QTLR were defined on nine Ovis aries chromosomes (OAR) by LDLA. The ratio between the ANOVA estimators of the QTL variance and the total phenotypic variance ranged from 0.0087 to 0.0176. QTL on OAR4, 12, 19, and 20 were the most significant. The combination of association analysis and functional annotation of sequence data did not highlight any putative causative mutations. None of the most significant SNPs showed a functional effect on genes’ transcript. However, in the most significant QTLR, we identified genes that contained polymorphisms with a high or moderate impact, were differentially expressed in previous studies, contributed to enrich the most represented GO process (regulation of immune system process, defense response). Among these, the most likely candidate genes were: TNFRSF1B and SELE on OAR12, IL5RA on OAR19, IL17A, IL17F, TRIM26, TRIM38, TNFRSF21, LOC101118999, VEGFA, and TNF on OAR20. This study performed on a large experimental population provides a list of candidate genes and polymorphisms which could be used in further validation studies. The expected advancements in the quality of the annotation of the ovine genome and the use of experimental designs based on sequence data and phenotypes from multiple breeds that show different LD extents and gametic phases may help to identify causative mutations.

中文翻译：

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基因组区域内推算序列数据的关联分析和功能注释影响通过LDLA方法在Sarda奶羊的核群中检测到的胃肠寄生虫抗性

胃肠道线虫（GIN）是放牧绵羊的主要健康问题之一。尽管已经记录了对 GIN 抗性的遗传变异性，但传统的选择因难以记录表型而受到阻碍，通常是粪卵计数 (FEC)。为了确定用于选择的连锁不平衡 (LD) 中的致病突变或标记，基于连锁不平衡-连锁分析 (LDLA) 对 4097 只母羊（来自 181 头公牛）进行了 FEC 数量性状基因座 (QTL) 的检测。用 OvineSNP50 Beadchip 进行基因分型。从种群中 56 只目标动物的全基因组序列中估算出已识别的 QTL 区域 (QTLR)。对已识别的 QTLR 中的估算多态性进行关联分析和功能注释，以查明对从本体分类中识别的候选基因或在先前研究中差异表达的候选基因具有潜在影响的功能变体。在对靠近的重要位置进行聚类后，LDLA 在九个绵羊羊染色体 (OAR) 上定义了十个 QTLR。QTL 方差的 ANOVA 估计值与总表型方差之间的比率范围为 0.0087 至 0.0176。OAR4、12、19 和 20 上的 QTL 是最显着的。序列数据的关联分析和功能注释的结合没有突出任何推定的致病突变。最重要的 SNP 都没有显示出对基因转录的功能影响。然而，在最显着的 QTLR 中，我们确定了包含具有高度或中等影响的多态性的基因，在先前的研究中差异表达，有助于丰富最具代表性的 GO 过程（免疫系统过程的调节，防御反应）。其中，最可能的候选基因是：OAR12 上的 TNFRSF1B 和 SELE、OAR19 上的 IL5RA、IL17A、IL17F、TRIM26、TRIM38、TNFRSF21、LOC101118999、VEGFA 和 OAR20 上的 TNF。这项在大型实验人群中进行的研究提供了可用于进一步验证研究的候选基因和多态性列表。绵羊基因组注释质量的预期进步以及基于显示不同 LD 范围和配子阶段的多个品种的序列数据和表型的实验设计的使用可能有助于识别致病突变。