TOLERANCE AND SUSCEPTIBILITY IN HEAVY METAL PATHOLOGY

描述：（根据申请人摘要改编）基于以下事实： 铅毒性是一个重大的人类健康问题，该提案 被设计来检查个体间的遗传基础， 对铅毒性作用的敏感性/抵抗力。而 多种因素可以并且确实影响铅的潜在毒性 暴露，明确的流行病学数据将某些基因型与不同 铅暴露导致的临床结局。实验方法 将使用黑腹果蝇作为测试生物体，因为它富含 与这种生物体相关的遗传知识， 分子水平，各种菌株的可用性， 突变体，并在许多情况下记录了与高等生物的相关性。 具体而言，设想了两个总体目标以导致 负责耐受性基因的鉴定和表征 （a）通过分离已经暴露在 X染色体;和（B）通过分离另外的遗传修饰剂， 耐铅表型传统遗传学与现代遗传学 将利用分子遗传学工具来实现这些目标。与 基因分离的果蝇，人类cDNA文库的搜索将 分离相关、类似或同源的人类基因。

DESCRIPTION: (Adapted for applicant's abstract) Based on the fact that lead toxicity is a significant human health problem, this proposal has been designed to examine the genetic basis for inter-individual susceptibility/resistance to the toxicological effects of lead. While multiple factors can and do affect the potential toxicity to lead exposure, clear epidemiological data link certain genotypes to different clinical outcomes resulting from lead exposure. The experimental approach will use Drosophila melanogaster as the test organism because of the rich genetic knowledge associated with this organism, ease of manipulation at the molecular level, availability of a wide variety of strains and mutants, and documented relevance in many cases to higher organisms. Specifically, two general aims are contemplated to lead to the identification and characterization of gene(s) responsible for tolerance to lead: (a) by isolating a lead resistance allele already uncovered on the X chromosome;and (b) by isolating additional genetic modifiers of lead tolerant phenotypes. Traditional classical genetics and modern molecular genetics tools will be used to achieve these aims. With the gene(s) isolated for Drosophila, searches of human cDNA libraries will be performed to isolate related, analogous or homologous human genes.