Genetics of Host Resistance to Chlamydia trachomatis

宿主对沙眼衣原体抗性的遗传学

• 批准号: 7174281
• 负责人: MICHAEL N STARNBACH
• 金额: $ 41.15万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7174281
• 关键词: Acute; Affect; Alleles; Animals; Bacterial Sexually Transmitted Diseases; Blindness; Bone Marrow; Candidate Disease Gene; Cells; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Chronic; Communicable Diseases; Complex; Development; Diagnostic; Disease; Dissection; Elements; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Host resistance; Human; Individual; Infection; Knock-out; Knowledge; Location; Maps; Modeling; Molecular; Mouse Strains; Mus; Outcome; Phenotype; Play; Population; Predisposition; Process; Quantitative Trait Loci; Research Personnel; Resistance; Resistance to infection; Role; Severities; Severity of illness; Sexually Transmitted Diseases; Source; Standards of Weights and Measures; Symptoms; Systemic infection; Testing; Transgenic Organisms; Transplantation; Vacuole; Variant; base; congenic; data modeling; design; gene function; genetic analysis; genome sequencing; human disease; mouse model; pathogen; positional cloning; programs; research study

DESCRIPTION (provided by applicant): Host genetic variation plays a large role in the outcome of infection. Therefore, genetic analysis of resistance to infectious disease can reveal genes important for affecting the severity of disease course. This type of genetic analysis has been very successful in the mouse for a variety of infection models, and this data has pointed the way to candidate genes that could affect human infections. For the proposed genetic experiments, we have decided to focus on mouse infections with the human pathogen Chlamydia trachomatis. It is a major cause of blindness in endemic regions, and may be the most common source of bacterial sexually transmitted disease in the world. Based on the results of studies of human and animal infections with Chlamydia, it seems likely that at least some of the variations in disease symptoms result from genetic differences in host susceptibility to distinct elements of chlamydial disease. Therefore, we want to study the role of host genetic background in the severity of Chlamydia infections, using a mouse model of a human chlamydial disease. For our first Aim, we will utilize mouse genetics as a means to refine the location of Quantitative Trait Loci (QTL) that influence the outcome of an acute systemic infection with C. trachomatis, which is designed to model elements of the human sexually transmitted disease called lymphogranulum venereum. For the second Aim, we will identify the genes that underlie the effects of those QTL. For the third Aim, we will study the genes isolated in the first 2 Aims, to determine their effects on intracellular bacterial replication. This project will attempt to define mouse genes that affect susceptibility to disease caused by infections with Chlamydia trachomatis. It is likely that humans will have similar gene functions that will influence similar susceptibilities to infectious disease. Since infections with Chlamydia trachomatis are common in the human population, it is possible that knowledge of these genes could help to design diagnostics or therapies for this infection.

描述（由申请人提供）：宿主遗传变异在感染的结果中起着重要作用。因此，对传染病的抗性的遗传分析可以揭示对影响疾病病程严重程度重要的基因。对于各种感染模型，这种类型的遗传分析在小鼠中非常成功，并且该数据指向了可能影响人类感染的候选基因。对于拟议的遗传实验，我们决定将重点放在人类病原体沙眼的小鼠感染上。它是流行地区失明的主要原因，可能是世界上最常见的性传播疾病的来源。根据对衣原体的人类和动物感染的研究结果，似乎至少有一些疾病症状的变化是由于宿主对衣原体疾病不同元素的遗传敏感性的遗传差异而引起的。因此，我们希望使用人衣原体疾病的小鼠模型研究宿主遗传背景在衣原体感染严重程度中的作用。为了我们的第一个目的，我们将利用小鼠遗传学来完善定量性状基因座（QTL）的位置，这些定量性状基因座（QTL）会影响急性系统性感染与沙眼曲霉的急性全身感染的结果，该急性全身性感染旨在模拟人类性传播疾病的元素，称为lymphogranulum torereum。为了第二个目标，我们将确定这些QTL影响的基因。对于第三个目标，我们将研究前两个目标中分离的基因，以确定它们对细胞内细菌复制的影响。 该项目将尝试定义小鼠基因，这些小鼠基因影响因沙眼衣原体引起的疾病易感性。人类可能具有类似的基因功能，会影响与传染病的类似敏感性。由于沙眼衣原体的感染在人群中很常见，因此这些基因的知识可能有助于为这种感染设计诊断或疗法。