项目名称： 不规则毛霉致原发性皮肤接合菌病的易感基因和毒力基因的筛选和验证

项目编号： No.81471905

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘维达

作者单位： 中国医学科学院

项目金额： 75万元

中文摘要： 不规则毛霉所致原发性慢性皮肤感染近20余年来在我国屡有报告，迄今累计报告已达20余例，而国外迄今仅亚洲报告3例。据我们对已发表病例资料分析，该菌所致的感染有如下临床特征：绝大多数患者为免疫健全者；极少引起非皮肤组织的深部感染；无明显其他毛霉具有的嗜血管性；虽不易致死但易致毁容或畸残。引起这些特征主要源于宿主防御因素还是菌种毒力因素抑或二者相互作用所致？拟在前期工作基础上，开展宿主和真菌两方面的致病基因研究：1、宿主易感基因：收集病例标本，采用外显子捕获测序、筛选候选易感基因、并通过家系其他成员和健康人群验证确定该感染的易感基因，并进行树突状细胞、单核细胞及动物模型不同水平的对比分析，明确该基因在疾病发生发展过程中的作用；2、真菌毒力基因：采用全基因组测序及比较基因组学和生物信息学技术，找出不规则毛霉的与致病可能相关的基因并加以功能验证。研究目的是为临床科学认识和有效防治该感染提供科学依据。

中文关键词： 不规则毛霉；皮肤接合菌病；易感基因；毒力基因；基因测序

英文摘要： The primary chronic skin infection caused by Mucor irregular in China in recent more than 20 years in the report, today reported so far have been about 20 cases, and Asia reported only 3 cases over the same period abroad. According to our analysis of published data, the clinical features of the infections caused by M. irregular are as follows : The vast majority of patients for immunocompetent; the deep infection of the non skin tissue caused by the fungi is very few；No obvious blood vessels invasion and tissue necrosis as in the infections caused by other Mucor species；The infection is not easily lead to death, but easy to disfigurement and disability. These clinical characteristics largely because of the host defense also be caused by the virulence factors from the fungal pathogen or caused by the host and the pathogen interaction between the two sides? On the basis of the preliminary works , we will study on two aspects, namely the susceptibility genes of the patients and the virulence genes of the M. irregular.1.the host susceptibility genes : collect the specimens of the cases,, and then using exon capture sequence and screening of the candidate genetic susceptibility, next verified to determine whether the infection susceptibility genes in healthy people and other members of the families. And by the analysis of the genes, proteins and immune cell function , clearly the role of genes in the infections development process. 2. using whole genome sequencing , the comparative genomics and bioinformatics technologies, find the virulence genes of M, irregular, such as ion metabolism and temperature control related genes and carry out functional verification. The purpose of this project is to provide a basis for clinical scientific understanding and effectively prevention and control the fungal infection.

英文关键词： Mucor irregular;cutaneous zygomycosis;susceptibility gene;virulence gene;genetic sequencing