A Linkage Map for Schistosoma mansoni

曼氏血吸虫连锁图谱

• 批准号: 7189294
• 负责人: Tim J Anderson
• 金额: $ 25.65万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-19 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7189294
• 关键词: Affect; Alleles; Archives; Biology; Capillary Electrophoresis; Chromosome Mapping; Chromosome Segregation; Chromosomes; Communities; DNA; Data; Development; Disease; Drug resistance; Facility Construction Funding Category; Female; Fluorescent in Situ Hybridization; Frequencies; Generations; Genes; Genetic; Genetic Crosses; Genetic Markers; Genetic Recombination; Genome; Genotype; Human; Individual; Karyotype; Knowledge; Label; Laboratories; Length; Life Cycle Stages; Maps; Measurement; Measures; Methodology; Methods; Microsatellite Repeats; Mining; Morbidity - disease rate; Mus; Optic Chiasm; Organism; Parasites; Partner in relationship; Pattern; Pharmacotherapy; Phenotype; Physical Chromosome Mapping; Polymerase Chain Reaction; Polymorphic Microsatellite Marker; Production; Productivity; Public Health; Quality of life; Quantitative Trait Loci; Range; Rate; Repetitive Sequence; Research; Research Personnel; Resolution; Resources; Sampling; Schistosoma; Schistosoma mansoni; Short Tandem Repeat; Snails; Specificity; Staging; Time; Variant; Virulence; Work; Yeasts; base; density; design; genetic analysis; genetic pedigree; genome sequencing; improved; male; man; mortality; research study; segregation; tool; trait; transmission process; vector

DESCRIPTION (provided by applicant): Schistosomes infect 200 million people worldwide causing extensive mortality and morbidity, while reducing productivity and quality of life. Schistosoma mansoni, one of the primary schistosome species that causes disease in man, shows heritable variation in many medically and epidemiologically relevant traits such as virulence, transmissibility, drug resistance, and infectivity to snail intermediate hosts. However, the genetic basis of variation in these traits remains unknown. Linkage mapping is a powerful and efficient methodology for locating genome regions that contain genes for heritable phenotypic traits. To use this approach we propose to develop the first linkage map for S. mansoni. We will develop this resource by conducting a cross between genetically divergent parasites in the laboratory and then genotyping parental, F1, and 90 F2 progeny using ~250 microsatellite markers mined from the genome sequence data. We will assign markers to linkage groups and estimate recombinational distance on chromosomes from segregation patterns of markers in the progeny. The map generated will be anchored to the S. mansoni karyotype by genotyping microsatellite markers that have been physically mapped by fluorescent in situ hybridization (FISH). We estimate that the map will have an average marker density of 5cM, based on cytological measures of chiasma frequencies. The linkage map will have multiple uses for schistosome biology: (1) Because markers are derived from existing genome sequence data, the map will assist in the assembly of the genome. (2) It will allow measurement of essential genetic parameters such as recombination rate and map length (3) Most importantly, it will provide an essential tool for linkage mapping of genes underlying important schistosome traits, such as host specificity, transmissibility, virulence, and drug resistance. The linkage map and archived DNA samples will be provided as a resource for the schistosome research community. Relevance of this research to public health. Knowledge of S. mansoni genes affecting host specificity, drug resistance, and virulence is critical for the development of drug therapies, and understanding parasite transmission patterns and interactions with snail vectors. Development of a linkage map will pave the way for finding these genes.

描述（由申请人提供）：血吸虫感染全世界 2 亿人，造成广泛的死亡和发病，同时降低生产力和生活质量。曼氏血吸虫是引起人类疾病的主要血吸虫种类之一，在许多医学和流行病学相关特征上表现出遗传变异，例如毒力、传播性、耐药性和对蜗牛中间宿主的感染性。然而，这些性状变异的遗传基础仍然未知。连锁图谱是一种强大而有效的方法，用于定位包含可遗传表型性状基因的基因组区域。为了使用这种方法，我们建议开发曼索尼沙门氏菌的第一个连锁图。我们将通过在实验室中对遗传差异的寄生虫进行杂交来开发这一资源，然后使用从基因组序列数据中挖掘的约 250 个微卫星标记对亲本、F1 和 90 F2 后代进行基因分型。我们将标记分配给连锁群，并根据后代中标记的分离模式估计染色体上的重组距离。生成的图谱将通过对微卫星标记进行基因分型来锚定曼氏沙门氏菌核型，这些微卫星标记已通过荧光原位杂交 (FISH) 进行物理定位。根据交叉频率的细胞学测量，我们估计该图谱的平均标记密度为 5cM。连锁图谱对于血吸虫生物学有多种用途：（1）由于标记源自现有的基因组序列数据，因此该图谱将有助于基因组的组装。 (2) 它将允许测量重要的遗传参数，如重组率和图谱长度。 (3) 最重要的是，它将为重要血吸虫性状的基因连锁图谱提供重要工具，如宿主特异性、传播性、毒力和耐药性。连锁图谱和存档的 DNA 样本将作为血吸虫研究界的资源提供。这项研究与公共卫生的相关性。了解影响宿主特异性、耐药性和毒力的曼氏链霉菌基因对于药物疗法的开发以及了解寄生虫传播模式和与蜗牛载体的相互作用至关重要。连锁图谱的开发将为寻找这些基因铺平道路。