GENOMIC DELETION AND DUPLICATION COVERAGE IN DROSOPHILA

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DESCRIPTION (provided by applicant): Functional genomic research in Drosophila melanogaster continues to provide discoveries important to the understanding of human development and the improvement of human health. The development of research tools that enhance the utility of Drosophila as a model organism will benefit the biomedical sciences in general. Although the Drosophila genome is now sequenced, fly geneticists tack complete arrays of chromosomal deletions and duplications, which would enable them to study the functions of genes in all chromosomal regions. As a service to the research community, scientists at the BDSC began a project to improve deletion and duplication coverage. To benefit from techniques developed and genetic strains constructed under a previous grant, they propose to: 1) continue screening for chromosomal deletions to provide essentially complete deletion coverage of the autosomes; 2) screen for chromosomal deletions to provide similarly complete deletion coverage of the X chromosome; and 3) to generate Y-linked duplications of X chromosomal segments to provide complete duplication coverage of the X chromosome. Cytologically large deletions providing novel genome coverage will be isolated by screening for chromosomal rearrangements involving pairs of P transposable element insertions catalyzed by P transposase. Haplolethal and haplosterile loci that have hindered the recovery of deletions in the past will be flanked by deletions to maximize genomic deletion coverage. Duplications will be generated in two steps: X inversions with a common distal tip breakpoint and multiple proximal breakpoints will be made using FLP-FRT technology and appended to Y chromosomes. These "X inversion + Y" chromosomes will be irradiated to recover large internal deletions extending from variable sites proximal to the X tip inversion breakpoint to within X heterochromatin. The resulting "X tip-variable duplicated X segment-X heterochromatin-Y" chromosomes will form multiple nested sets of Y-linked X duplications for the entire X chromosome. Strains developed in this project will be distributed by the BDSC, where they will receive immediate and widespread use.