Development of an E. histolytica Multilocus Genotyping System

溶组织内阿米巴多位点基因分型系统的开发

基本信息

批准号：
8727438
负责人：
CAROL A GILCHRIST
金额：
$ 18.71万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-28 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8727438
关键词：
1 year old Address Africa Age Amebiasis Amebic Liver Abscess Amebic colitis Amoeba genus Area Asia Bangladesh Biology Child Clinical Communicable Diseases Data Development Diagnostic Diarrhea Disease Disease Outcome Dysentery Entamoeba histolytica Enteral Environment Environmental Risk Factor Feces Gene Expression Profile Gene Expression Regulation Genes Genetic Genetic Markers Genetic Polymorphism Genetic Variation Genome Genomics Genotype Health Height Hereditary Disease High-Throughput Nucleotide Sequencing Individual Infection Institutes International Knowledge Life Link Liver Abscess Locales Longitudinal Studies Malnutrition Maryland Measures Methods Minority Molecular Multivariate Analysis Mutation National Institute of Allergy and Infectious Disease Outcome Paper Parasites Patients Phenotype Population Predisposition Research Research Design Research Personnel Risk Factors Sampling Sampling Studies Scientist Single Nucleotide Polymorphism Slum Step Tests System Universities Variant Virginia Virulence Virulent Work advanced disease biobank cell motility enteric pathogen field study innovation international center killings leptin receptor mortality next generation sequencing professor public health relevance repository

项目摘要

DESCRIPTION (provided by applicant: One million children die before their fifth birthday from diarrhea. The eukaryotic parasite Entamoeba histolytica is one of the top 10 causes of diarrhea in the developing world. The outcome of an E. histolytica infection is variable and can result in either asymptomatic carriage, immediate or latent disease. Our preliminary studies suggest that there is a link between parasite genetics and disease; we identified two single nucleotide polymorphisms (SNPs) infrequent in diarrheal isolates but common in strains that asymptomatically colonize children. Our hypothesis is that variation in the E. histolytica genome influences virulence and disease outcome. Innovation: The extensive genetic polymorphism found in trophozoites in clinical isolates, have made it difficult to identify the genetic changes that define the virulence potential of this parasite. The existence of a biorepository of E. histolytica positive stool samples (collected during a longitudinal study of enteric disease) and advances in high-throughput sequencing, make it now possible for us to study this parasite at a population level. Approach: An ongoing study of the enteric pathogens infecting children who live in the urban slum of Mirpur, Bangladesh, has collected E. histolytica positive stool samples. These were obtained from both asymptomatically colonizing ameba and those responsible for E. histolytica associated diarrhea. In this study we will first sequence the whole genome and transcriptome of cultured strains to identify common E. histolytica SNPs. We will then use the study samples to investigate whether an association exists between the virulent amebic strains and the parasite SNP genotype. Investigator: Dr. Gilchrist is an Assistant Professor of Research Division of Infectious Diseases and International Health. Her research has focused on using molecular methods to understand the biology and pathogenic phenotype of enteric parasites. She is co- author on the paper describing the sequenced E. histolytica genome, and for her studies on the gene regulation of E. histolytica motility she developed the first E. histolytica Affymetrix microarrays. Environment: Dr. Gilchrist's lab is in a uniquely supportive environment, as there is substantial institutional expertise, and support for work on enteric diseases of global significance at the Division of Infectious Diseases at the University of Virginia. Her collaborator include Dr. R. Haque at the International Centre for Diarrhoeal Diseases Research, Dhaka, Bangladesh (ICDDR,B) and Dr. W. Petri at UVA who are co-PI's of an ongoing longitudinal study of the enteric pathogens infecting children in Dhaka, Bangladesh. Dr. E. Caler, leader of the NIAID E. histolytica genomic and sequencing project at JCVI, Maryland will collaborate on the sequencing of ameba strains. Dr. Gilchrist's other colleagues at UVA include Dr. I. K. M. Ali, who developed the original E. histolytica genotyping system, and Dr. E. Houpt, an expert in the development of enteric pathogen diagnostics.

描述（由申请人提供：一百万儿童在五岁之前死于腹泻。真核寄生虫溶组织阿米巴是发展中国家腹泻的十大原因之一。溶组织阿米巴感染的结果是可变的，可能导致我们的初步研究表明，寄生虫遗传学与疾病之间存在联系；我们发现了两种单核苷酸多态性 (SNP)。在腹泻分离株中不常见，但在无症状定植的儿童菌株中常见。我们的假设是，溶组织内阿米巴基因组的变异会影响毒力和疾病结果。创新：在临床分离株的滋养体中发现的广泛遗传多态性使得鉴定该菌株变得困难。定义该寄生虫毒力潜力的基因变化存在溶组织内阿米巴阳性粪便样本的生物储存库（在纵向研究中收集）。肠道疾病）和高通量测序的进步，使我们现在有可能在群体水平上研究这种寄生虫。方法：一项正在进行的对感染孟加拉国米尔普尔城市贫民窟儿童的肠道病原体的研究收集了溶组织内阿米巴阳性粪便样本。这些样本是从无症状定植的阿米巴原虫和导致溶组织内阿米巴原虫相关腹泻的阿米巴原虫中获得的。在这项研究中，我们将首先对培养菌株的全基因组和转录组进行测序，以鉴定常见的溶组织内阿米巴 SNP。然后，我们将使用研究样本来调查阿米巴毒株与寄生虫 SNP 基因型之间是否存在关联。调查员：Gilchrist博士是传染病和国际卫生研究部的助理教授。她的研究重点是使用分子方法来了解肠道寄生虫的生物学和致病表型。她是描述溶组织内阿米巴基因组测序论文的合著者，并且为了研究溶组织内阿米巴运动性的基因调控，她开发了第一个溶组织内阿米巴 Affymetrix 微阵列。环境：Gilchrist 博士的实验室拥有得天独厚的支持性环境，拥有丰富的机构专业知识，并为全球肠道疾病研究工作提供支持。在弗吉尼亚大学传染病科具有重要意义。她的合作者包括孟加拉国达卡国际腹泻病研究中心 (ICDDR,B) 的 R. Haque 博士和 UVA 的 W. Petri 博士，他们是一项正在进行的感染儿童肠道病原体的纵向研究的共同负责人。孟加拉国达卡。马里兰州 JCVI 的 NIAID 溶组织内阿米巴基因组和测序项目负责人 E. Caler 博士将合作对阿米巴菌株进行测序。 Gilchrist 博士在 UVA 的其他同事包括 I. K. M. Ali 博士（他开发了最初的溶组织内阿米巴基因分型系统）和 E. Houpt 博士（肠道病原体诊断开发专家）。