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. ? ? ?
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