Mutations in genes can affect the encoded proteins in multiple ways, and some of these effects are counterintuitive. As for any other knowledge, students must create their own deep understanding of the Central Dogma. Students may not develop this understanding because they have limited opportunity to practice manipulating DNA sequences and classifying their effects. Such practice can improve student appreciation for the myriad possible effects of DNA change (mutation) on amino acid sequence. In this Lesson, a series of scaffolded exercises provides this opportunity. Students first identify gene sequences from an online database, create their own insertion/deletion mutations, and predict the effects. Students then use a web-based tool to translate and observe the effect of the mutation on protein sequence. Subsequent comparison of predicted and observed effects employs the chi-square test. Discussion of results with peers involves categorizing the types of possible effects. The lesson concludes with an exercise asking students to create a mutation with an intended effect on the protein. Together, the exercises integrate quantitative reasoning and statistical analysis, information literacy, and multiple Bloom's learning levels. Student progress is monitored using three formative and three summative assessments.