A Linkage Map for Schistosoma mansoni

描述（由申请人提供）：血吸虫感染全球2亿人，造成广泛的死亡率和发病率，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寄生虫种之一，在许多医学和流行病学相关性状如毒力、传播性、耐药性和对蜗牛中间宿主的感染性方面显示出可遗传的变异。然而，这些性状变异的遗传基础仍然未知。连锁作图是一种定位基因组区域的强大而有效的方法，该区域包含遗传表型性状的基因。为了使用这种方法，我们建议开发第一个连锁图谱的S。mansoni我们将通过在实验室中进行遗传上不同的寄生虫之间的杂交来开发这种资源，然后使用从基因组序列数据中挖掘的~250个微卫星标记对亲本、F1和90个F2后代进行基因分型。我们将分配标记连锁群和估计染色体上的重组距离从分离模式的标记在后代。生成的地图将锚定到S。mansoni核型的基因分型微卫星标记，已被物理映射的荧光原位杂交（FISH）。我们估计，该地图将有一个平均标记密度为5cM，根据细胞学措施的交叉频率。连锁图谱将在染色体生物学中有多种用途：（1）由于标记来源于现有的基因组序列数据，因此图谱将有助于基因组的组装。(2)它将允许测量基本的遗传参数，如重组率和图谱长度（3）最重要的是，它将提供一个必要的工具，用于重要的染色体性状，如宿主特异性，遗传性，毒力和耐药性的基因连锁图谱。连锁图和存档的DNA样本将作为一种资源提供给棘手的研究界。这项研究与公共卫生的相关性。S的知识。影响宿主特异性、耐药性和毒力的mansoni基因对于药物疗法的开发以及理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。

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.