大骨节病与类风湿关节炎基因表达差异和下游凋亡Caspase网络机制对比研究

The proposed research plan will adopt micro-array analysis and database optimization algorithm genetic information extraction (SVM\TSP) and other techniques to study the differences in gene expression and downstream apoptosis Caspase pathway mechanism between Kashin-Beck disease(KBD) and rheumatoid arthritis(RA) with a focus on KBD genetic diagnosis software and multi-step decision-making model. The biological model of the early diagnosis of KBD will be built by complementing the gene data of KBD and other common forms of osteopathia and expounding the similarities and differences of the apoptotic mechanism of downstream Caspase pathway. The research will not only help to lay the foundation for the theoretical basis of the KBD pathogenesis and early differential diagnosis, but also to build the model for the early diagnosis of KBD .The comparison of differential apoptosis Caspase mechanism map of KBD will provide ground and direction for gene therapy and drug intervention of KBD. The results may give additional information on the pathogenesis of other forms of arthritis and their early diagnosis. Keeping in view the high burden of disease and poor quality of life associated with KBD, this study may prove to be of a great scientific significance and of high practical utility.

本课题针对大骨节病（KBD）与类风湿关节炎（RA）基因特征差异、KBD早期基因诊断以及与RA下游Caspase凋亡通路机制异同问题，采用基因芯片分析、数据库优化算法、基因提取（SUV\TSP）模型等技术，研究KBD与RA差异基因谱及凋亡下游Caspase机制，KBD基因诊断软件及多步决策模型等内容。完善KBD与常见骨病特有的差异基因谱并阐明下游Caspase凋亡机制异同，构建出诊断KBD的生物学模型。不但为阐明KBD发病机制、早期鉴别诊断防治奠定了理论基础，而且构建的KBD早期诊断模型和与RA Caspase机制差异，为KBD进行基因治疗与防治、药物干预等提供了依据和方向；对研究其它骨病机制和早期诊断提供新思路，具有重要的科学意义和社会实用价值。

大骨节病（KBD）与常见骨病的基因差异研究一直是近年来研究热点。本研究重点针对KBD与类风湿关节炎（RA）基因差异、KBD早期基因诊断以及与RA发病机制通路机制异同问题，采用转录组测序分析、数据库优化算法、基因提取（SUV\TSP）模型等技术，研究KBD与RA差异基因谱、发病机制异同、特征基因诊断多步决策模型等内容。本次研究使用最新技术Illumina Nextseq 500对KBD和RA关节软骨基因进行转录组测序，筛选出关键差异基因1568个，其中RA上调基因1336个，KBD上调基因 232个；约120G相关数据片段，平均每个病例约800万个配对reads；证实RA和炎症以及免疫异常相关，而KBD与Wnt- 和 BMP-信号通路异常有关；通过SVM等算法重新将KBD与OA进行诊断模型构建并得出关键核心基因。以上结果对阐明KBD发病机制、早期鉴别诊断防治奠定了理论基础，为KBD进行基因治疗与防治、药物干预等提供了依据和方向；对研究其它骨病机制和早期诊断提供新思路，具有重要的科学意义和社会实用价值。