Disease resilience is the ability of an animal to maintain productive performance under disease conditions and is an important selection target. In pig breeding programs, disease resilience must be evaluated on selection candidates without exposing them to disease. To identify potential genetic indicators for disease resilience that can be measured on selection candidates, we focused on the blood transcriptome of 1594 young healthy pigs with subsequent records on disease resilience. Transcriptome data were obtained by 3’mRNA sequencing and genotype data were from a 650 K genotyping array. Heritabilities of the expression of 16,545 genes were estimated, of which 5665 genes showed significant estimates of heritability (p < 0.05), ranging from 0.05 to 0.90, with or without accounting for white blood cell composition. Genes with heritable expression levels were spread across chromosomes, but were enriched in the swine leukocyte antigen region (average estimate > 0.2). The correlation of heritability estimates with the corresponding estimates obtained for genes expressed in human blood was weak but a sizable number of genes with heritable expression levels overlapped. Genes with heritable expression levels were significantly enriched for biological processes such as cell activation, immune system process, stress response, and leukocyte activation, and were involved in various disease annotations such as RNA virus infection, including SARS-Cov2, as well as liver disease, and inflammation. To estimate genetic correlations with disease resilience, 3205 genotyped pigs, including the 1594 pigs with transcriptome data, were evaluated for disease resilience following their exposure to a natural polymicrobial disease challenge. Significant genetic correlations (p < 0.05) were observed with all resilience phenotypes, although few exceeded expected false discovery rates. Enrichment analysis of genes ranked by estimates of genetic correlations with resilience phenotypes revealed significance for biological processes such as regulation of cytokines, including interleukins and interferons, and chaperone mediated protein folding. These results suggest that expression levels in the blood of young healthy pigs for genes in biological pathways related to immunity and endoplasmic reticulum stress have potential to be used as genetic indicator traits to select for disease resilience.

中文翻译：

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对年轻健康猪的血液转录组进行遗传分析以提高疾病抵抗力


抗病能力是动物在疾病条件下保持生产性能的能力，是重要的选择目标。在生猪育种计划中，必须在不让候选猪接触疾病的情况下评估其抗病能力。为了确定可对候选猪进行测量的疾病恢复力的潜在遗传指标，我们重点研究了 1594 头年轻健康猪的血液转录组以及随后的疾病恢复力记录。转录组数据通过 3'mRNA 测序获得，基因型数据来自 650 K 基因分型阵列。估计了 16,545 个基因表达的遗传力，其中 5665 个基因显示出显着的遗传力估计值 (p < 0.05)，范围从 0.05 到 0.90，无论是否考虑白细胞组成。具有可遗传表达水平的基因分布在染色体上，但在猪白细胞抗原区域富集（平均估计> 0.2）。遗传力估计值与人类血液中表达的基因获得的相应估计值的相关性很弱，但相当数量的具有可遗传表达水平的基因重叠。具有可遗传表达水平的基因在细胞激活、免疫系统过程、应激反应和白细胞激活等生物过程中显着富集，并参与各种疾病注释，例如RNA病毒感染（包括SARS-Cov2）以及肝脏疾病和炎症。为了估计与疾病恢复力的遗传相关性，对 3205 头基因型猪（包括具有转录组数据的 1594 头猪）在暴露于自然多种微生物疾病挑战后的疾病恢复力进行了评估。显着的遗传相关性 (p < 0.05）在所有弹性表型中都被观察到，尽管很少有超过预期的错误发现率。通过估计与弹性表型的遗传相关性对基因进行富集分析，揭示了对生物过程的重要性，例如细胞因子（包括白细胞介素和干扰素）的调节以及分子伴侣介导的蛋白质折叠。这些结果表明，年轻健康猪血液中与免疫和内质网应激相关的生物途径基因的表达水平有可能用作选择疾病恢复能力的遗传指标性状。