TOLERANCE AND SUSCEPTIBILITY IN HEAVY METAL PATHOLOGY

重金属病理学的耐受性和敏感性

• 批准号: 2444231
• 负责人: IAIN L CARTWRIGHT
• 金额: $ 18.2万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2444231
• 关键词: Drosophilidae; complementary DNA; genetic library; heavy metals; metal poisoning; molecular cloning; nucleic acid sequence; pharmacogenetics; polymerase chain reaction; sex chromosomes; toxicology; transposon /insertion element

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.

描述：（适用于申请人的摘要），基于以下事实 铅毒性是一个重大的人类健康问题，该提议已有 被设计为检查个体间的遗传基础 对铅的毒理作用的敏感性/抗性。尽管 多种因素可以并且确实会影响潜在的毒性 暴露，清晰的流行病学数据将某些基因型连接到不同 铅暴露引起的临床结果。实验方法 由于富裕 与这种生物相关的遗传知识，易于操纵 分子水平，各种各样的菌株的可用性 突变体，并在许多情况下记录了与更高生物体的相关性。 具体来说，考虑了两个一般目标，以导致 负责耐受性的基因的识别和表征 铅：（a）通过隔离铅阻力等位基因已被发现 X染色体；（b）通过隔离其他遗传修饰符 铅耐受性表型。传统的古典遗传学和现代 分子遗传学工具将用于实现这些目标。与 分离为果蝇分离的基因，对人cDNA库的搜索将 进行以分离相关，类似或同源的人类基因。

项目成果

Analysis of Drosophila chromatin structure in vivo.

果蝇体内染色质结构分析。

• DOI: 10.1016/s0076-6879(99)04028-8
• 发表时间: 1999
• 期刊: Methods in enzymology
• 作者: Cartwright,IL;Cryderman,DE;Gilmour,DS;Pile,LA;Wallrath,LL;Weber,JA;Elgin,SC
• 通讯作者: Elgin,SC