Burden tests can be used to map causal genes for a simple metabolic trait in an exome-sequenced polyploid mutant population

Forward genetic screens are an excellent tool to assign gene function, but it is often necessary to employ map-based cloning to identify the causal genes. This can be laborious and represents a bottleneck in plant fundamental and applied research. With advances in DNA technology, it is becoming increasingly affordable to sequence large populations. Krasileva et al. (2017) exome sequenced tetraploid and hexaploid wheat ethyl methanesulfonate (EMS) mutagenized populations, primarily to facilitate reverse genetic screens. Gene redundancy allows a very high mutant load of 35–40 mutations per kilobase, and the populations of ~1500 and ~1200 lines each harbour ~22–23 missense or truncation mutations per gene. Here, we show that burden tests, a simple form of rare-variant association analysis developed for human disease genetics (Lee et al., 2014), can be used to identify causal genes in the hexaploid wheat (Triticum aestivum) cv. Cadenza mutant population, without the need for map-based cloning.