Comparison of primary DNA sequences between closely related organisms is a powerful tool for identifying important, conserved genetic sequences, and the function of unknown sequences may be inferred from protein motifs and degrees of relatedness to other members of the same family. Another approach to the functional dissection of a genome is to induce mutations in genes and observe their effects on development and fertility. In the September 4 Nature, Benjamin Kile and colleagues at the Baylor College of Medicine—whose laboratory originally engineered a balancer chromosome—show how balancer chromosomes can be utilized in mice for the purposes of maintaining the integrity of lethal mutant stocks and for use as a crucial tool in mutagenesis screening (Nature, 425:81-86, September 4, 2003).