A gene map for Biomphalaria glabrata, a S. mansoni host

描述（由申请人提供）：血吸虫如何在蜗牛宿主中存活或被消灭的基本问题对血吸虫病的流行病学具有重要意义。前人的研究表明，光螺的遗传变异在曼氏血吸虫（Schistosoma mansoni）的壳内发育中起着重要作用。从遗传上选择具有抗性或易感的蜗牛种群，为鉴定螺/寄生虫关系中重要的标记和基因提供了宝贵的资源。我们的目标是使用完善的分子工具，研究具有稳定但不同易感表型的蜗牛种群，以鉴定和表征那些在抵抗或完全支持血吸虫感染中起关键作用的蜗牛基因。抗性和易感蜗牛DNA的多态性应该使我们能够有效地分离针对蜗牛/寄生虫关系中涉及的序列的探针。此外，还将利用多态标记对钉螺后代的遗传能力进行检测，以区分钉螺的抗性和易感性。通过从暴露的和正常的抗性和易感的蜗牛幼螺中生成抑制减法杂交（SSH）文库，并通过从抗性和易感的蜗牛幼螺（寄生虫感染）中筛选可用的cDNA探针蜗牛微阵列，我们希望在这种蜗牛宿主中确定控制这些不同感染表型的基因。为了通过FISH对光秃秃双歧杆菌染色体进行位置定位，我们将使用（作为探针）BAG克隆，对应于从微阵列/减法研究中鉴定的转录本。我们的总体策略是减少重复标记的流入，并结合在DNA和RNA水平上获得的有用信息，以解剖相对较大的光斑拟虫基因组中涉及寄生虫发育或破坏的相关基因产物。

DESCRIPTION (provided by applicant): The fundamental issue of how a schistosome survives, or is targeted for destruction, in a snail host has important implications for the epidemiology of schistosomiasis. Preceding groundwork clearly showed that genetic variations in the snail Biomphalaria glabrata play a major role in the intramolluscan development of the parasitic helminth Schistosoma mansoni. Snail stocks that were genetically selected as either parasite resistant or susceptible have provided us with valuable resources for identifying markers as well as gene(s) important in the snail/parasite relationship. Our objective is to use well-established molecular tools, studying defined snail stocks with stable but different susceptibility phenotypes, to identify and characterize those snail genes that play a critical role in resisting, or fully supporting, a schistosome infection. Polymorphisms in resistant vs. susceptible snail DNA should enable us to efficiently isolate probes targeting those sequences involved in the snail/parasite relationship. Use will also be made of examining the heritability of polymorphic markers in progeny snails that segregate for resistance or susceptibility. By generating suppression subtraction hybridization (SSH) libraries from exposed vs normal resistant and susceptible juvenile snails and, by screening an available snail microarray with cDNA probes from resistant and susceptible juvenile snails ( parasite infection), we hope to identify genes that govern these different infection phenotypes in this snail-host. For positional mapping of B. glabrata chromosomes by FISH, we will use (as probes) BAG clones, corresponding to transcripts identified from the microarray/subtraction studies. Our overall strategy is to reduce the inflow of repetitive markers and combine useful information gained at both DNA and RNA levels to dissect relevant gene products involved in parasite development or destruction coded for, within the relatively large B. glabrata genome.