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Drosophila Genetic Reference Panel Team Publishes Initial Findings

NEW YORK (GenomeWeb News) – In today's issue of Nature, a large team of researchers from the US, Spain, and the UK describe a genotype-phenotype resource developed for the fruit fly.

The Drosophila Genetic Reference Panel, or DGRP, includes genome sequences, population genomic data, and other data for almost 200 Drosophila melanogaster lines. The result is a community resource that North Carolina State University geneticist Trudy Mackay, co-first author on the Nature study, called a "living library of genetic variation."

"Until now, we had the information necessary to understand what makes a fruit fly different from, say, a mosquito," Mackay said in a statement. "Now we understand the genetic differences responsible for individual variation, or why one strain of flies lives longer or is more aggressive than another strain."

From analyses of DGRP data so far, researchers have already learned about some of the polymorphism and evolutionary patterns in the fruit fly genome. Through genome-wide association studies of the inbred fruit fly populations, they've also identified candidate variants that appear to contribute to traits such as startle response, starvation resistance, and recovery time after a chill-induced coma.

"One of the grand challenges of biology is to understand how genetic variants and environmental factors interact to produce variation in complex phenotypes … within populations," Mackay said. "This effort has been stymied by the lack of knowledge of all genetic variants in a population of a genetically tractable model organism."

She and her colleagues decided to tackle this problem for D. melanogaster, a commonly used model organism. Using wild flies collected in Raleigh, the team established 192 inbred D. melanogaster lines for inclusion in the DGRP.

The resource "contains a representative sample of naturally segregating genetic variation, has an ultra-fine-grained recombination map suitable for precise localization of causal variants, and has almost complete euchromatic sequence information," they wrote.

At the Biology of Genomes meeting at Cold Spring Harbor last year, Julien Ayroles described research underway with wild-derived fruit flies from the DGRP as well as additional synthetic lines developed through random mating of DGRP flies over many generations. Ayroles, a co-author on the new study, was a graduate student with Mackay and co-first author Eric Stone, also at North Carolina State University.

Related projects known as the Drosophila Gene Disruption Project and Drosophila modENCODE are also underway.

The current study represents data generated prior to data freeze 1.0 of the project, which includes information on 168 Drosophila lines re-sequenced using Illumina and/or Roche 454 instruments. Of these, 129 lines were sequenced exclusively on Illumina instruments, 10 lines were sequenced with the 454 platform alone, and 29 lines were sequenced using both Illumina and 454.

The team's analyses of the sequences so far have uncovered millions of SNPs. They also identified hundreds of thousands of microsatellite polymorphisms, insertions and deletions, and variation involving tandem repeats and transposable elements.

Sifting through Drosophila population data so far, for example, the team saw a dip in polymorphism density around the centromeres of autosomal chromosomes. When they compared patterns on X chromosomes with those on autosomes, meanwhile, investigators saw evidence of fewer polymorphisms but more recombination and faster evolution.

Their association studies — focusing on chill-coma, startle, and starvation-related traits — implicated a slew of candidate SNPs that seem to account for much of the phenotypic variation observed for these traits.

"The DRPG is an ideal resource for systems genetics analyses of the relationship between molecular variation, causal molecular networks, and genetic variation for complex traits," the team concluded, "and will anchor evolutionary studies in comparison with sequenced Drosophila species to assess to what extent variation within a species corresponds to variation among species."

Flies from DGRP lines are available through the Bloomington Drosophila Stock Center. Sequence and variant call data, phenotypic information on the lines, and tools used for population and GWAS analyses are also being made available through a Baylor College of Medicine Human Genome Sequencing Center website and/or sites maintained by the Mackay and Mittelman labs at North Carolina State University and Virginia Tech, respectively.