We propose to identify candidate longevity assurance genes (LAGs) using Quantitative Trait Locus-mapping (QTL-mapping) in laboratory populations of Drosophila melanogaster. QTL-mapping estimates the number, chromosomal locations, and magnitudes of effect of genes that cause variation in quantitative characters. Mapping will require 40,000 single-fly PCRs per year. Once candidate chromosomal regions have been identified, we will increase the density of marker loci in regions of interest, to facilitate cloning and sequencing of QTLs. The evolutionary role of QTLs in heterogeneous populations will be studied in two ways: by creating a """"""""marker-selected"""""""" population from the base population, and by examining the trajectories of linked and unlinked marker loci in heterogeneous populations that are subjected to artificial selection for increased longevity. Notable aspects of the proposed research are: (i) Novelty of approach; QTL-mapping has not been applied to Drosophila, but has been very successful in plants. (ii) New technology; marker loci will be identified using RAPDs, a PCR-based technique that allows the assay of many loci in single flies. (iii) The experimental design has been optimized by Monte Carlo simulation of QTL-mapping experiments. (iv) Collaboration; PI and post-doc will attend NIA workshops, collaborate with the Luckinbill lab at Wayne State University in construction of stocks, and share recombinant- inbred lines with other labs.
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