Two Flavors of Bulk Segregant Analysis in Yeast
Genetic mapping methods typically rely upon genotyping many individuals in a mapping population. In contrast, bulk segregant analysis looks for biases in genotype in phenotyped pools of segregants. For relatively strong and genetically simple traits, it can be a fast, inexpensive approach. Although it is technically possible to use many genotyping platforms, microarray-based methods are convenient for their genome-wide coverage, ease of use, and quantitative output. Also, precise knowledge of polymorphic sites is not required. I present two methods for bulk segregant analysis using microarrays, one based on hybridization differences between polymorphisms, and the other using an enzymatic method for enriching identical by descent segments of the genome. The first method requires specialized array platforms, while the second, genomic mismatch scanning (GMS), is compatible with any microarray. Although the methods presented are with yeast, most steps are equivalent for other organisms.
Key wordsBulk segregant analysis Genomic mismatch scanning Pooled mapping
The author would like to thank Matthew Brauer for joint development of these methods. Appreciation also goes to Mark Rose and Elbert Chiang for collaboration on mapping data shown in Fig. 2. Caroline McCoach, Pat Brown, and David Botstein contributed to development of GMS protocols, and USB provided preproduction MutHLS enzymes. This work was supported in part by P50 GM071508 to the Lewis-Sigler Institute at Princeton University.
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