钩端螺旋体遗传多态性和微进化研究

项目名称： 钩端螺旋体遗传多态性和微进化研究

项目编号： No.81471968

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： 徐颖华

作者单位： 中国食品药品检定研究院

项目金额： 70万元

中文摘要： 钩端螺旋体病（简称钩体病）是由致病性钩端螺旋体（简称钩体）引起的一种急性人兽共患传染病。近年来随着钩体病流行趋势的改变，世界各地报道的钩体感染病例数逐渐增多，给当地人民健康和畜牧业生产造成了严重的威胁。因此，了解其分子流行病学趋势、种群结构和微进化对于防控该传染病具有重要意义。本研究拟通过收集不同国家地区、不同时期的代表性钩体，尽可能的代表钩体的种群多样性；综合使用全基因组Solexa测序、SNP分析、MLST、MLVA等研究技术，分析大量关键基因或位点的遗传多态性，了解我国流行的钩体基因组变异特点和分子流行趋势，阐述各菌株/菌型的系统发育关系；认识单碱基突变、基因获得、基因缺失在基因组微进化中的作用，构建钩体遗传多态性数据库；探究主要流行菌型的遗传基础和毒力进化机制，从而更加深入掌握钩体微进化特征和规律，为钩体分子分型、溯源以及新疫苗的研制奠定理论基础。

中文关键词： 钩端螺旋体；自然疫源性传染病；遗传多态性；微进化；病原溯源

英文摘要： Leptospirosis is an acute natural focal infectious disease caused by pathogenic Leptospires. In recent years, with the change of leptospirosis epidemiological trends, the reported cases of leptospirosis infection have gradually been increased throughout the world, which result a serious threat for the people health and livestock production. Therefore, it is very important for the prevention and control of leptospirosis that understanding the molecular epidemiological trends, population structure and microevolution of Leptospires. In this study, many Leptospira isolated from different periods and countries will be collected, which assumed to represent the diversity of the population. The whole-genome Solexa sequencing, SNP analysis, MLST and MLVA will be used and genetic polymorphisms at many key genes and locis will be analyzed. These study results will help us understand the characteristics of genomic variations and molecular trends of the epidemic Leptospires in China. The phylogenetic relationship among different strains(types) will then be investigated for insight into the role of single base mutation, gene acquisition, gene deletion at Leptospira microevoluation. The genetic polymorphism database of Leptospires will be built. It will be explored for the genetic basis and evolution mechanisms of virulence of the main epidemic isolates, which facilitate us in-depth understanding of the microevolution of leptospires. Taken together, these data will offer the basis of molecular typing, pathogenic tractability and the development of new vaccines in the future.

英文关键词： Leptospira;Natural focal infectious disease;Genetic polymorphisms;Microevolution;Pathogen traceability