A Linkage Map for Schistosoma mansoni

描述（由申请人提供）：全世界有2亿人感染血吸虫，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（Schistosoma mansoni）是导致人类疾病的主要血吸虫物种之一，在许多医学和流行病学相关特征上表现出遗传变异，如毒力、传播力、耐药性和对蜗牛中间宿主的传染性。然而，这些性状变异的遗传基础尚不清楚。连锁定位是一种强大而有效的方法，用于定位包含遗传表型性状基因的基因组区域。为了使用这种方法，我们建议开发第一个mansoni的连锁图谱。我们将在实验室中对遗传差异的寄生虫进行杂交，然后利用从基因组序列数据中提取的约250个微卫星标记对亲代、F1和90个F2后代进行基因分型，从而开发这一资源。我们将把标记分配给连锁群，并从后代中标记的分离模式估计染色体上的重组距离。通过荧光原位杂交（FISH）物理定位的微卫星标记进行基因分型，将生成的图谱固定在曼氏血吸虫核型上。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。该连锁图谱将在血吸虫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，因此该图谱将有助于基因组的组装。最重要的是，它将为血吸虫重要性状（如宿主特异性、传播性、毒力和耐药性）的基因连锁作图提供必要的工具。链接图和存档的DNA样本将作为血吸虫研究界的资源提供。本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mansoni基因对药物治疗的发展、了解寄生虫传播模式以及与蜗牛载体的相互作用至关重要。连锁图谱的发展将为找到这些基因铺平道路。

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.