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Drosophila Resource Finding Favor For Genotype-Phenotype Studies

By Andrea Anderson

COLD SPRING HARBOR, NY (GenomeWeb News) – In addition to characterizing nearly 200 wild-derived fruit fly lines, researchers involved with the Drosophila Genetic Reference Panel are developing a hyper-recombinant Drosophila population to help validate and complement findings generated from this DGRP panel.

During a session at the Biology of Genomes meeting here yesterday, North Carolina State University genetics researcher Julien Ayroles described the progress being made using DGRP community resources to link genotype to phenotype.

The 192 Drosophila lines in the DGRP reference panel were derived from wild fruit flies collected at a farmer's market in Raleigh that were subsequently crossed and inbred in the lab over many generations, he explained.

So far, 162 of the lines have been sequenced using Illumina sequencing technology and 40 lines have been sequenced using Roche 454 technology. The Baylor College of Medicine Human Genome Sequencing Center announced an initial data freeze and release last August for DGRP lines sequenced on the Illumina platform.

Using this genome sequence data, researchers have been working to track down Drosophila SNPs that can be employed for association mapping of various fly traits such as copulation latency, startle response, and starvation resistance, Ayroles said.

Lines in the DGRP have already been characterized based on dozens of phenotypes, ranging from behavioral patterns to metabolic and transcriptional features.

During his talk, Ayroles touched on patterns being detected in association studies — as well as some of the challenges associated with finding and validating these genotype-phenotype ties in the fly panel.

He also described how he and his colleagues are using a synthetic population of flies, dubbed Flyland, to help test hypotheses stemming from experiments in the original fly panel — and look at the contributions that relatively rare genetic variants make to fruit fly phenotypes.

Flyland was generated by crossing flies from a subset of inbred DGRP lines in a "round robin" manner, Ayroles explained, followed by random mating over more than 90 generations.

Researchers are in the process of studying flies from phenotypic extremes in this population, first doing assays to assess various fly features and then sequencing flies in the top and bottom 10 percent of the distribution curve for a given phenotype.

For example, Ayroles described some initial findings from a starvation stress study in the Flyland population in which 300 of the top starvation-resistant flies and 300 of the most starvation-sensitive flies were sequenced in an effort to track down prominent starvation response-related genes.