Genetic Dissection: Imprinting Drosophila melanogaster

遗传解剖：印记果蝇

• 批准号: 6526887
• 负责人: KEITH A MAGGERT
• 金额: $ 0.54万
• 依托单位: UNIVERSITY OF UTAH
• 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/6526887
• 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.

染色体保留其起源的记忆，无论是父亲还是母亲。此类信息以独立于序列的方式进行编码，因为在不同生物体中相同的序列的行为可能有所不同。标记在整个生物体的躯体中都是稳定的，只是在传播到后代之前要重置。这种烙印的解释可能会影响染色体的调节方式 - 无论是在发育中丢失，还是链接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单一遗传性疾病的异常情况。未能维持这种烙印也与后来发作的疾病有关，例如威尔姆斯的肿瘤。我将使用最近在果蝇中印刷的近来表征的例子，以研究对印迹的要求和调节。首先，我将筛选基因组中的突变，这些突变会影响印记，维护和解释的能力。通过使用跨越大部分基因组的缺陷。我将能够发现印记的剂量依赖性修饰符。其次，我将表征启动印迹的要求，以在p元素的y连锁插入上发生。使用一组此类插入物，我将确定插入插入物之间的相似之处，并尝试映射构成烙印所需的序列或染色体结构要求。