H.PYLORI POPULATION GENETICS AND GENOME EVOLUTION

幽门螺杆菌群体遗传学和基因组进化

• 批准号: 6743656
• 负责人: DOUGLAS Eugene BERG
• 金额: $ 30.97万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6743656
• 关键词: Asians; Helicobacter; Japanese; South America; alleles; bacterial genetics; biochemical evolution; clinical research; endoscopy; family genetics; feces analysis; gene expression; gene mutation; genetic polymorphism; genetic recombination; genome; genotype; gerbil /jird; human subject; laboratory mouse; molecular genetics; polymerase chain reaction; population genetics; racial /ethnic difference

DESCRIPTION (provided by applicant): Helicobacter pylori (Hp) are one of the most genetically diverse of bacterial species. Our preliminary DNA-based phylogenetic analyses showed that genotypes of Hp in Spain differ from those in East Asia, and that genotypes of Hp from Peruvians in Lima are mostly Spanish-like. The studies proposed for this grant period have four main specific aims. AIM 1. To better understand Hp genetic diversity and genome evolution. We will extend current phylogenetic studies to Hp strains from other Amerind people in Latin America, to test predictions that most such Hp strains will also be Spanish-like at most loci. Any Hp population found to be rich in alleles unlike those of Spain will be examined further. Hp from elsewhere in Europe, Asia and Africa will also be studied (i) to better understand Hp population genetic structure worldwide, (ii) test predictions that Hp gene pools in Japan and Spain represent subsets of more genetically diverse East Asian and European gene pools, respectively. AIM 2. To identify naturally occurring allele differences that affect fitness and understand their basis. We will test the generality of our finding that East Asian-type alleles of the comB9 gene are abundant in Hp from Amerinds in Lima, and test if this reflects selection. More generally, additional cases of unusual abundance of particular alleles or genes will be investigated to identify bacterial traits important in specificity of host interaction. Effects on fitness of candidate genes or alleles will be examined using genetically manipulated rodent-adapted Hp strains and mouse and gerbil infection models. AIM 3. To examine Hp evolutionary dynamics within family units, Hp strains from parents and children in individual Peruvian families will be genotyped to gain insights into relatedness, intrafamilial vs. community transmission, and mutation, recombination, and selection on Hp in societies where overall risks of infection are high. AIM 4. To detect transmission between communities, mixed infection, and potential for recombination. Hp from Japanese Peruvians will be genotyped to detect (i) retention of ancestral Japanese-type genes, vs. community acquisition of putative Native Peruvian (Spanish-type) strains; (ii) mixed infections, especially involving strains of different ethnic origins, (iii) extent of recombination in a brief time frame, and (iv) selection for particular genes or alleles.

描述（由申请人提供）：幽门螺杆菌（HP）是细菌种类最多样化的物种之一。 我们的初步基于DNA的系统发育分析表明，西班牙HP的基因型与东亚的基因型不同，而来自利马的秘鲁人的HP基因型主要类似于西班牙语。在本赠款期间提出的研究具有四个主要的特定目标。 目标1。更好地了解HP遗传多样性和基因组进化。 我们将将当前的系统发育研究扩展到来自拉丁美洲其他Amerind人群的HP菌株，以测试大多数此类HP菌株在大多数基因座中也将是西班牙型菌株。与西班牙不同的任何惠普人群不同的等位基因都富含等位基因。 （i）也将研究来自欧洲其他地方的惠普，以更好地了解全球HP种群遗传结构，（ii）测试预测日本和西班牙的HP基因库分别代表了更具遗传多样性的东亚和欧洲基因库的亚集。目的2。确定影响适应性并理解其基础的自然存在的等位基因差异。我们将测试我们发现的一般性，即Comb9基因的东亚型等位基因在利马的Amerinds中丰富，并测试这是否反映了选择。更一般而言，将研究其他特定等位基因或基因的其他情况的其他病例，以确定对宿主相互作用特异性重要的细菌特征。 将使用遗传操纵的啮齿动物适应的HP菌株以及小鼠和沙鼠感染模型对候选基因或等位基因的适应性的影响进行检查。目的3。要检查家庭单位内的HP进化动态，将对秘鲁家族的父母和儿童的HP菌株进行基因分型，以深入了解相关性，家庭内传播与社区传播，突变，重组以及对整体感染风险很高的社会中的HP选择。目标4。检测社区，混合感染和重组潜力之间的传播。 日本秘鲁人的惠普将进行基因分型，以检测（i）保留祖先日本型基因，与社区收购推定的原生秘鲁（西班牙型）菌株； （ii）混合感染，尤其是涉及不同种族起源的菌株的混合感染，（iii）在短时间内重组的程度，以及（iv）选择特定基因或等位基因。