Charting the Genotype-Phenotype Map: Lessons From Drosophila

The Drosophila melanogaster Genetic Reference Panel (DGRP) consists of 205 sequenced inbred strains derived from the Raleigh, NC population. The DGRP is a community resource for genome wide association (GWA) analyses for quantitative traits in a scenario where all single nucleotide polymorphisms are genotyped. The large amount of quantitative genetic variation, lack of population structure and rapid local decay of linkage disequilibrium in the DGRP present a favorable scenario for identifying candidate causal genes and even polymorphisms affecting complex traits. Further, we have derived a large outbred, advanced intercross population from a subset of 40 DGRP lines (Flyland) to test multi-locus predictions derived from the DGRP. We performed bulk segregant sequencing for pools of individuals from the Flyland population with extreme phenotypes, and mapped variants associated with the traits with significant allele frequency differences between the high and low pools. I will discuss inferences about the contribution of rare and common alleles, and of additive and epistatic gene action, obtained from analyses of genetic architecture in the DGRP and Flyland populations, and the implications of the Drosophila data for studies in other species, including humans.