Genetic Dissection: Imprinting Drosophila melanogaster

遗传解剖：印记果蝇

• 批准号: 6492867
• 负责人: KEITH A MAGGERT
• 金额: $ 2.95万
• 依托单位: STOWERS INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6492867
• 关键词: Drosophilidae; arthropod genetics; gene interaction; gene mutation; genetic mapping; genomic imprinting; nucleic acid sequence; postdoctoral investigator; sex linked trait; site directed mutagenesis

Chromosomes retain memory of their origin, whether paternal or maternal. Such information is coded in a sequence-independent fashion, as identical sequences may behave differently in different organisms. The marking is stable throughout the soma of an organism, only to be reset prior to transmission to progeny. The interpretation of this imprint may affect how a chromosome is regulated - whether it is lost in development, or whether expression of linked genes is modulated or repressed. This phenomenon leads to the unusual case of uniparentally- inherited disorders in mammals. The failure to maintain this imprint has also been linked with later-onset diseases, such as Wilms' Tumors. I will use a recently-characterized example of imprinting in Drosophila in order to study the requirements for, and regulation of, imprinting. First, I will screen for mutations in the genome that affect the ability for an imprint to be set, maintained, and interpreted. By using deficiencies that span most of the genome. I will be able to uncover dose-dependent modifiers of imprinting. Second, I will characterize the requirements for the initiation of imprinting to occur on a Y-linked insertion of a P- element. Using a set of such inserts, I will determine the similarities between inserts that become imprinted, and attempt to map sequence or chromosome structure requirements necessary for imprinting to become established.

染色体保留着其起源的记忆，无论是父亲还是母亲。这些信息以序列独立的方式编码，因为相同的序列在不同的生物体中可能表现不同。该标记在生物体的整个索马中是稳定的，只是在传递给后代之前被重置。对这种印记的解释可能会影响染色体的调节方式--它是否在发育中丢失，或者连锁基因的表达是否受到调节或抑制。这种现象导致了哺乳动物中不寻常的单亲遗传疾病。未能保持这种印记也与迟发性疾病有关，如Wilms' Tumors。我将使用一个最近的特点，在果蝇的印记的例子，以研究的要求，和调节，印记。首先，我将筛选基因组中的突变，这些突变会影响印记的设置、维持和解释。利用大部分基因组的缺陷。我就能发现剂量依赖的印记调节剂。第二，我将描述在Y-连接的P-元件插入上发生印记起始的要求。使用一组这样的插入物，我将确定成为印记的插入物之间的相似性，并试图映射印记建立所需的序列或染色体结构要求。