Leibniz Institute for Farm Animal Biology (FBN), Institute for Genome Biology, Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany.
Leibniz Institute for Farm Animal Biology (FBN), Institute of Genetics and Biometry, Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany.
Sci Rep. 2019 Sep 10;9(1):13038. doi: 10.1038/s41598-019-49521-2.
The hypothalamic-pituitary-adrenal (HPA) axis is an important component of neuroendocrine stress regulation and coping behavior. Transcriptome profiles of the hypothalamus and adrenal gland were assessed to identify molecular pathways and candidate genes for coping behavior in pigs. Ten each of high- (HR) and low- (LR) reactive pigs (n = 20) were selected for expression profiling based haplotype information of a prominent QTL-region on SSC12 discovered in our previous genome-wide association study (GWAS) on coping behavior. Comparing the HR and LR pigs showed 692 differentially expressed genes (DEGs) in the adrenal gland and 853 DEGs in the hypothalamus, respectively. Interestingly, 47% (17 out of 36) of DEGs found in both tissues were located in GWAS regions identified on SSC12, indicating that there are significant functional positional candidate genes for coping behaviour. Pathway analysis assigned DEGs to glucocorticoid receptor signaling in the adrenal gland. Furthermore, oxidative phosphorylation, mitochondrial dysfunction, and NGF signaling as well as cholecystokinin/Gastrin-mediated were identified in the hypothalamus. We narrowed the list of candidate genes in GWAS regions by analyzing their DEGs in the HPA axis. The top identified transcripts, including ATP1B2, AURKB, MPDU1 and NDEL1 provide evidence for molecular correlates of coping behavior in GWAS regions.
下丘脑-垂体-肾上腺 (HPA) 轴是神经内分泌应激调节和应对行为的重要组成部分。评估下丘脑和肾上腺的转录组谱，以确定应对行为的分子途径和候选基因。根据我们之前关于应对行为的全基因组关联研究 (GWAS) 中在 SSC12 上发现的一个突出 QTL 区域的单倍型信息，选择了 10 头高反应性 (HR) 和低反应性 (LR) 猪 (n = 20) 进行表达谱分析。比较 HR 和 LR 猪发现，肾上腺中有 692 个差异表达基因 (DEG)，下丘脑中有 853 个 DEG。有趣的是，在这两个组织中发现的 47%（36 个中的 17 个）差异表达基因位于 SSC12 上确定的 GWAS 区域，表明存在与应对行为相关的显著功能候选基因。通路分析将 DEG 分配给肾上腺中的糖皮质激素受体信号转导。此外，在下丘脑中还鉴定到氧化磷酸化、线粒体功能障碍和 NGF 信号转导以及胆囊收缩素/胃泌素介导的信号转导。我们通过分析 HPA 轴中 GWAS 区域的 DEG 来缩小候选基因列表。鉴定到的顶级转录本，包括 ATP1B2、AURKB、MPDU1 和 NDEL1，为 GWAS 区域的应对行为的分子相关性提供了证据。
