Comparative Genomics of Major Clonal Groups of a Lyme Disease Pathogen

莱姆病病原体主要克隆群的比较基因组学

基本信息

批准号：
8049058
负责人：
WEIGANG QIU
金额：
$ 11.29万
依托单位：
HUNTER COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8049058
关键词：
Affect Antigens Bacteria Beryllium Bioinformatics Black-legged Tick Borrelia burgdorferi Borrelia burgdorferi Group Case Study Centers for Disease Control and Prevention (U.S.)Characteristics Chromosome Mapping Chromosomes Code Collaborations Communities Complex DNA Sequence Data Deer Tick Development Disease Elements Evolution Functional RNA Funding Gene Expression Regulation Gene Family Genes Genetic Genome Genomics Goals Homologous Gene Human Imagery Immunity Individual Infection Inflammatory Informatics Intergenic Sequence Internet Joints Lead Lipoproteins Lyme Disease Maps Molecular Mutation National Institute of Allergy and Infectious Disease Natural Selections Neuraxis North America Nucleotides Open Reading Frames Order Spirochaetales Outcome Pathogenesis Phenotype Phylogenetic Analysis Phylogeny Plasmids Population Prevalence Qualifying Regulator Genes Relative (related person)Research Research Infrastructure Research Personnel Retrieval Sequence Alignment Single Nucleotide Polymorphism Sister Skin Specificity Staging Sum Surface Testing Ticks Tissues United States United States National Institutes of Health Variant Vector-transmitted infectious disease Vertebral column Vertebrates Virulence Width Work Yang base career college comparative comparative genomics design gene conservation genome sequencing geographic difference improved pathogen preference success therapeutic vaccine tool development web site

项目摘要

DESCRIPTION (provided by applicant): Lyme disease is the most prevalent and a fast spreading vector-borne infectious disease in the U.S. It is caused by a spirochetal bacterium Borrelia burgdorferi and transmitted by the deer tick Ixodes scapularis. At least 15 genetically distinct clonal groups of the Lyme disease pathogen are circulating in the northeastern U.S., where over 80% of the Lyme disease cases are reported annually. These clonal groups differ in their wildlife prevalence and human pathogenecity. In 2006, a group of six investigators including the PI have initiated a NIH/NIAID-funded 2-year project producing the whole-genome sequences of 17 B. burgdorferi isolates, with the goal of identifying the genetic basis of clone variations in environmental invasiveness and human virulence. Here, the PI proposes a study to complete the goal of the NIAID whole-genome sequencing project by performing the comparative genome analysis of 12 most common clonal groups. Specific aims are: First, we will identify strain-specific genome changes in a phylogenetic framework. We will identify and align the main chromosomes, orthologous plasmids, and orthologous coding sequences. We will infer a genome-based phylogeny based on chromosomal DNA sequences, so that the strain differences in genome content, genome organization, and DNA sequences can be mapped to different stages during the evolutionary diversification of these clonal groups. Second, we will distinguish more consequential (e.g., adaptive) genomic changes from the lesser (e.g., random) ones by testing for the influence of natural selection. We will identify intergenic sequences important for gene regulation by their sequence conservation, genes critical for B. burgdorferi adaptation (e.g., surface lipoproteins conferring escape from host immunity) by their high non-synonymous nucleotide substitution rates relative to the synonymous rates, genes associated with initial adaptive clonal divergence by comparing the most recently diverged sister clones. Third, we will develop and maintain a website to facilitate the public dissemination of B. burgdorferi comparative genome information, such as genomic changes specific to a high-virulence clonal group. It is unknown why some strains of the Lyme disease bacteria are more pathogenic than others. We will compare the genomes of high- and low-virulence strains to identify the genes contributing to pathogenecity. Virulence-related genome elements are prime targets for designing therapeutics and vaccines.

描述（由申请人提供）：莱姆病是美国最普遍，是一种快速传播的载体传染病，是由螺旋体细菌Borlelia burgdorferi引起的，并由鹿tick tick ixodes scapularis传播。在美国东北部，莱姆病病原体的至少有15个遗传不同的克隆群正在循环，每年有80％以上的莱姆病病例。这些克隆人群的野生动植物患病率和人类病原体不同。 2006年，包括PI在内的六个研究人员启动了NIH/NIAID资助的2年项目，产生了17 B. Burgdorferi分离株的整个基因组序列，目的是确定克隆在环境入侵性和人类毒力中的克隆变化的遗传基础。在这里，PI提出了一项研究，通过对12个最常见的克隆人组进行比较基因组分析来完成NIAID全基因组测序项目的目标。具体目的是：首先，我们将在系统发育框架中确定特异性基因组变化。我们将识别和对齐主要的染色体，直系同源质粒和直系同源的编码序列。我们将根据染色体DNA序列推断基于基因组的系统发育，以便在这些克隆组的进化多样化期间，可以将基因组含量，基因组组织和DNA序列的应变差异映射到不同的阶段。其次，我们将通过测试自然选择的影响来区分较小的（例如随机）基因组变化（例如，自适应）基因组变化。我们将通过其序列保守来确定对基因调节的重要基因序列，对于B. burgdorferi适应至关重要的基因（例如，通过其高非同义核苷酸取代率相对于同一性的适应性地球蛋白的基因，通过与最初的姐姐相关的基因，通过其高的非同义核苷酸取代速率来赋予宿主免疫的表面脂蛋白，从而使宿主免疫逃脱。第三，我们将开发和维护一个网站，以促进B. burgdorferi比较基因组信息的公众传播，例如特定于高病毒克隆人群的基因组变化。尚不清楚莱姆病细菌的某些菌株比其他菌株更具致病性。我们将比较高病毒菌株的基因组，以鉴定导致病原体的基因。与毒力相关的基因组元素是设计治疗和疫苗的主要靶标。