Progress 10/01/10 to 09/30/11
Outputs
OUTPUTS: My proposed work focuses on recombination rate variation in Drosophila. In this reporting period, we have generated 10,000 recombinant males with a single crossover in a defined 2.1 Mb region of the D. melanogaster X chromosome. These recombinants represent meiotic events occurring in 16 different strains from two different populations. We will be sequencing these individual flies for this target region to localize recombination breakpoints. Pilot genotyping data are forthcoming. We have also made much progress in our population genetic inference of recombination rate. The first step in this project is to define relevant, Drosophila-specific parameter space. We have conducted a series of simulations to this end, which are currently running. With respect to the final project, which is the estimation of recombination rate in a mapping panel of D. melanogaster, we have nearly completed the construction of the mutant lines that will be used for this experiment. We expect to begin this project in the Fall. PARTICIPANTS: Stephanie Ruzsa (part-time research support specialist) Matt Robinson (graduate student) TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
The impacts of this work are broad and far-reaching. With respect to fine-scale mapping of recombination rate, our data will yield 16 independent estimates of the recombination map, providing key information regarding the population-level variability of ultrafine-scale crossover distribution in D. melanogaster, about which nothing is known. As nothing is known regarding the underlying cause(s) of population-level variation in recombination rate in Drosophila, this line of inquiry is extremely exciting and has tremendous potential for uncovering the key genomic features that govern fine-scale recombination rate variation in this model system. In addition, the comparison of resulting data from the two distinct populations will allow us to test whether the features governing intrapopulation variability in recombination rate are the same as those modulating interpopulation variability. Further, comparing these features to those identified in other systems such as humans, for instance, will illuminate the degree to which the factors modulating recombination rate variation are grossly conserved across eukaryotes. With respect to the population genomic inference of recombination rate,understanding the scale at which recombination intensity varies is critical. With the advent of genomics, we are now poised to dissect the relationship between genotype and phenotype with unparalleled precision. Doing so relies heavily on genome-wide association studies (GWAS), which can facilitate discovery of allelic variants underlying phenotypes of interest. The efficacy of such studies, however, is dependent on the degree of linkage disequilibrium (LD), or the non-random association of alleles at multiple loci, in the sample. Because recombination essentially removes LD by breaking down the non-random association of alleles at linked sites, determining the scale at which recombination intensity is heterogeneous will necessarily inform mapping studies and linkage-based analyses. This is particularly important in D. melanogaster, which is often used as a model for association studies. Finally, with respect to characterizing genome-level variability in recombination rate, the data yielded in our studies will yield a comprehensive estimate of population-level variability in recombination rate in D. melanogaster. This work will provide much-needed insight into the genetic basis of this variation by identifying SNPs statistically associated with recombination rate variation that will make excellent candidates for functional validation. Finally, our results will greatly contribute to our understanding of key questions about the genetic basis of complex traits.
Publications
- No publications reported this period
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