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Genetic Dissection: Imprinting Drosophila melanogaster

$48,148F32FY2003GMNIH

University Of Utah, Salt Lake City UT

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Abstract

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.

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