GameteMaker: A Web-Accessible Genetic Mapping Simulation Program that Enables Students to Connect Mutant Phenotypes to Underlying, DNA Sequence-Based Genotypes

Genetic linkage guides all manner of approaches to gene discovery, from map-based cloning to QTL and GWAS analyses. I will describe a web-based genetic mapping simulation program, GameteMaker, that enables students in advanced high school and undergraduate settings to conduct virtual gene mapping experiments (http://sim.fpscgenetics.org). The sim presents students with images of mutant and corresponding wt phenotypes in the form of segregating F2 populations from which they will select some number for inclusion in a mapping population. Students select markers from a genome-wide collection of actual or potential PCR-based molecular marker assays to infer the linkage relationship between mutant and marker loci by inspection of virtual agarose gel images. Upon discovery of linkage, students follow an iterative process of additional marker assays and three point cross analyses to narrow the genomic interval that the logic of genetics demands must contain the causitive mutant locus. Having winnowed the interval to a size small enough to include a manageable number of candidate loci, students can transition from the sim server view functional annotations by using a genome browser and, ultimately, to compare DNA sequences of wt and mutant alleles to infer the location, nature, and likely consequences of observed sequence differences. The GameteMaker mapping sim makes use of mutants and molecular markers applicable to the FPsc variety of rapid-cycling Brassica rapa but can accommodate mapping in virtually any model organism for which mutant loci and map data are available.