Genetic Dissection: Imprinting Drosophila melanogaster

染色体保留着它们起源的记忆，无论是父系还是母系。这种信息是以与序列无关的方式编码的，因为相同的序列在不同的生物体中可能表现不同。在生物体的整个胞体中，标记是稳定的，只是在传递给后代之前重新设置。对这种印记的解释可能会影响染色体的调控方式--无论它是在发育过程中丢失，还是相关基因的表达受到调节或抑制。这一现象导致了哺乳动物中罕见的单亲遗传疾病。未能保持这种印记也与较晚发病的疾病有关，如肾母细胞瘤。我将使用一个最近在果蝇身上刻画的印记的例子来研究印记的要求和调节。首先，我将筛选基因组中的突变，这些突变会影响印记的设定、维护和解释能力。通过利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修饰物。其次，我将描述在P-元件的Y-连接插入上发生印迹起始的要求。使用一组这样的插入物，我将确定印记的插入物之间的相似性，并尝试绘制印记建立所需的序列或染色体结构要求。

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.