PT  - JOURNAL ARTICLE
AU  - John E Pool
TI  - Genetic Mapping by Bulk Segregant Analysis in Drosophila: Experimental Design and Simulation-Based Inference
AID  - 10.1101/057984
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 057984
4099  - http://biorxiv.org/content/early/2016/06/09/057984.short
4100  - http://biorxiv.org/content/early/2016/06/09/057984.full
AB  - Identifying the genomic regions that underlie complex phenotypic variation is a key challenge in modern biology. Many approaches to quantitative trait locus mapping in animal and plant species suffer from limited power and genomic resolution. Here, I investigate whether bulk segregant analysis (BSA), which has been successfully applied for yeast, may have utility in the genomic era for trait mapping in Drosophila (and other organisms that can be experimentally bred in similar numbers). I perform simulations to investigate the statistical signal of a quantitative trait locus (QTL) in a wide range of BSA and introgression mapping (IM) experiments. BSA consistently provides more accurate mapping signals than IM (in addition to allowing the mapping of multiple traits from the same experimental population). The performance of BSA and IM is maximized by having multiple independent crosses, more generations of interbreeding, larger numbers of breeding individuals, and greater genotyping effort, but is less affected by the proportion of individuals selected for phenotypic extreme pools. I also introduce a prototype analysis method for Simulation-based Inference for BSA Mapping (SIBSAM). This method identifies significant QTLs and estimates their genomic confidence intervals and relative effect sizes. Importantly, it also tests whether overlapping peaks should be considered as two distinct QTLs. This approach will facilitate improved trait mapping in Drosophila and other species for which hundreds or thousands of offspring (but not millions) can be studied.