PDF(Pubmed)
Abstract：
BACKGROUND: Atherosclerosis is a chronic cardiovascular disease of great concern. However, it is difficult to establish a direct connection between conventional small animal models and clinical practice. The pig\'s genome, physiology, and anatomy reflect human biology better than other laboratory animals, which is crucial for studying the pathogenesis of atherosclerosis.
METHODS: We used whole-genome sequencing data from nine Bama minipigs to perform a genome-wide linkage analysis, and further used bioinformatic tools to filter and identify underlying candidate genes. Candidate gene function prediction was performed using the online prediction tool STRING 12.0. Immunohistochemistry and immunofluorescence were used to detect the expression of proteins encoded by candidate genes.
RESULTS: We mapped differential single nucleotide polymorphisms (SNPs) to genes and obtained a total of 102 differential genes, then we used GO and KEGG pathway enrichment analysis to identify four candidate genes, including SLA-1, SLA-2, SLA-3, and TAP2. nsSNPs cause changes in the primary and tertiary structures of SLA-I and TAP2 proteins, the primary structures of these two proteins have undergone amino acid changes, and the tertiary structures also show slight changes. In addition, immunohistochemistry and immunofluorescence results showed that the expression changes of TAP2 protein in coronary arteries showed a trend of increasing from the middle layer to the inner layer.
CONCLUSIONS: We have identified SLA-I and TAP2 as potential susceptibility genes of atherosclerosis, highlighting the importance of antigen processing and immune response in atherogenesis.
METHODS: We used whole-genome sequencing data from nine Bama minipigs to perform a genome-wide linkage analysis, and further used bioinformatic tools to filter and identify underlying candidate genes. Candidate gene function prediction was performed using the online prediction tool STRING 12.0. Immunohistochemistry and immunofluorescence were used to detect the expression of proteins encoded by candidate genes.
RESULTS: We mapped differential single nucleotide polymorphisms (SNPs) to genes and obtained a total of 102 differential genes, then we used GO and KEGG pathway enrichment analysis to identify four candidate genes, including SLA-1, SLA-2, SLA-3, and TAP2. nsSNPs cause changes in the primary and tertiary structures of SLA-I and TAP2 proteins, the primary structures of these two proteins have undergone amino acid changes, and the tertiary structures also show slight changes. In addition, immunohistochemistry and immunofluorescence results showed that the expression changes of TAP2 protein in coronary arteries showed a trend of increasing from the middle layer to the inner layer.
CONCLUSIONS: We have identified SLA-I and TAP2 as potential susceptibility genes of atherosclerosis, highlighting the importance of antigen processing and immune response in atherogenesis.
摘要：
背景：动脉粥样硬化是一种备受关注的慢性心血管疾病。然而,传统的小动物模型与临床实践之间很难建立直接的联系。猪的基因组,生理学,解剖学比其他实验动物更好地反映人类生物学，这对于研究动脉粥样硬化的发病机制至关重要。
方法：我们使用来自9只巴马小型猪的全基因组测序数据进行全基因组连锁分析，并进一步使用生物信息学工具来过滤和识别潜在的候选基因。使用在线预测工具STRING12.0进行候选基因功能预测。免疫组织化学和免疫荧光用于检测候选基因编码的蛋白质的表达。
结果：我们将差异单核苷酸多态性（SNP）定位到基因上，共获得102个差异基因，然后我们使用GO和KEGG途径富集分析来鉴定四个候选基因，包括SLA-1、SLA-2、SLA-3和TAP2。nsSNP引起SLA-I和TAP2蛋白的一级和三级结构的变化，这两种蛋白质的初级结构经历了氨基酸变化，三级结构也显示出轻微的变化。此外,免疫组化和免疫荧光结果显示，TAP2蛋白在冠状动脉中的表达变化从中层到内层呈增加趋势。
结论：我们已经确定SLA-I和TAP2是动脉粥样硬化的潜在易感基因，强调抗原处理和免疫反应在动脉粥样硬化形成中的重要性。
方法：我们使用来自9只巴马小型猪的全基因组测序数据进行全基因组连锁分析，并进一步使用生物信息学工具来过滤和识别潜在的候选基因。使用在线预测工具STRING12.0进行候选基因功能预测。免疫组织化学和免疫荧光用于检测候选基因编码的蛋白质的表达。
结果：我们将差异单核苷酸多态性（SNP）定位到基因上，共获得102个差异基因，然后我们使用GO和KEGG途径富集分析来鉴定四个候选基因，包括SLA-1、SLA-2、SLA-3和TAP2。nsSNP引起SLA-I和TAP2蛋白的一级和三级结构的变化，这两种蛋白质的初级结构经历了氨基酸变化，三级结构也显示出轻微的变化。此外,免疫组化和免疫荧光结果显示，TAP2蛋白在冠状动脉中的表达变化从中层到内层呈增加趋势。
结论：我们已经确定SLA-I和TAP2是动脉粥样硬化的潜在易感基因，强调抗原处理和免疫反应在动脉粥样硬化形成中的重要性。
