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成为破坏的目标这一基本问题对血吸虫病的流行病学具有重要影响。以前的基础工作清楚地表明，蜗牛的遗传变异在曼氏血吸虫寄生蠕虫的软体内发育中起着重要作用。从基因上选择的抗寄生虫或易感钉螺种群为我们提供了宝贵的资源来寻找在钉螺/寄生虫关系中起重要作用的标记和基因(S)。我们的目标是使用成熟的分子工具，研究具有稳定但不同易感性表型的已确定的钉螺种群，以识别和表征那些在抵抗或完全支持血吸虫感染方面发挥关键作用的蜗牛基因。抗性蜗牛DNA与敏感蜗牛DNA的多态应该使我们能够有效地分离出针对涉及蜗牛/寄生虫关系的序列的探针。此外，还将研究分离抗性或易感性的后代蜗牛的多态标记的遗传力。为了用FISH技术定位光滑假单胞菌的染色体，我们将使用袋状克隆(作为探针)，与从微阵列/消减研究中鉴定的转录本相对应。我们的总体战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，在相对较大的光滑假单胞菌基因组中剖析参与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.