Characterization of functional/structural constraints operating on the Drosophila genome

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Chromosomes, the cellular entities that carry genes, can suffer modifications in their structure due to breakages and reattachments in new configurations. These breakages do not occur at random: some chromosome regions are prone to participate in chromosomal rearrangements while others are seldom affected. The reasons for these differences in susceptibility among chromosome regions are unclear. The current notion is that genes that work cooperatively or that have common molecular requirements are clustered in particular chromosome regions. It is thought that the viability and/or fertility of the organism can be impaired if these regions are disrupted by rearrangements. In humans, multiple diseases correlate with rearrangements of particular chromosome regions. Interestingly, those chromosome regions are intact in healthy individuals, an observation that also applies to other vertebrate species. This grant funds the first rigorous experimental test to understand the consequences of disrupting these delicate, ultra-conserved genomic regions. The work will use the fruit fly Drosophila, which is one of the best model organisms to understand the consequences of chromosomal rearrangements. Drosophila chromosomes possess the same kind of delicate, ultra-conserved regions as vertebrates do. In addition, Drosophila researchers have molecular tools to induce precise chromosomal rearrangements and to subsequently monitor their effects on the organism. The principal investigator plans to disrupt these special chromosome regions of Drosophila in order to analyze the consequences. The research is likely to have implications for understanding human genetic diseases. Furthermore, this grant will train undergraduate students and postdoctoral fellows in advanced concepts of genetics.