Agile Genetics: Single gene resolution without the fuss.

Abstract

Gene discovery reveals new biology, expands the utility of marker-assisted selection, and enables targeted mutagenesis. Still, such discoveries can take over a decade. We present a general strategy, "Agile Genetics," that uses nested, structured populations to overcome common limits on gene resolution. Extensive simulation work on realistic genetic architectures shows that, at population sizes of >5000 samples, single gene-resolution can be achieved using bulk segregant pools. At this scale, read depth and technical replication become major drivers of resolution. Emerging enrichment methods to address coverage are on the horizon; we describe one possibility - iterative depth sequencing (ID-seq). In addition, graph-based pangenomics in experimental populations will continue to maximize accuracy and improve interpretation. Based on this merger of agronomic scale with molecular and bioinformatic innovation, we predict a new age of rapid gene discovery.