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The long-lasting success of forward genetic screens relies on the simple molecular basis of the characterized phenotypes, which are typically caused by mutations in single genes. Mapping the location of causal mutations using genetic crosses has traditionally been a complex, multistep procedure, but next-generation sequencing now allows the rapid identification of causal mutations at single-nucleotide resolution even in complex genetic backgrounds.
(Schneeberger, 2014) Using next-generation sequencing to isolate mutant genes from forward genetic screens. Nat Rev Genet.