Traditional genetic screens performed in fruit flies. (a) Crossing scheme used to generate fruit flies containing mutant genes. Lines represent genomic DNA. Male fruit flies are fed a DNA-damaging agent or subjected to x-ray mutagenesis to induce random mutations (m) and then bred in mass with females containing a marked balancer chromosome (represented by dark black lines). Single F1 males are bred again with females containing a balancer chromosome to generate F2 male and female fruit flies carrying the same mutation. F2 siblings are backcrossed with each other to generate a balanced stock (50% of offspring) and produce F3 progeny that have a mutation in both copies of the gene (25%). Mutant progeny (m/m) are screened for defects. Fruit flies containing two copies of the balancer chromosome will die (25%). (b) Crossing scheme for modifier screens. Male fruit flies containing a previous mutation over a balancer chromosome are mutagenized as above and crossed with females carrying the same mutation. Offspring carrying a new mutation (m2) and mutant for both copies of the original mutation (m2; m/m) are compared to flies deficient for the original mutations (m/m) to determine if the defect is more severe (enhanced), less severe (suppressed), or has no effect. Enhanced and suppressed phenotypes suggest a genetic interaction between the two genes.
