A zebrafish module for genetic problem-solving

Teaching Mendelian genetics through problem-solving remains a challenge as students often struggle to connect foundational rules with the open-ended reasoning required for experimental design. To bridge this gap, we developed a 3-week, problem-based laboratory module for a large undergraduate course (~180 students) using wild-type zebrafish and three pigmentation mutants (nacre, roy, and casper) to guide students stepwise from observation to genetic inference. The module unfolds iteratively: students first learn rigorous phenotypic discrimination and data collection. They then receive a cross of unknown parental genotypes, quantify progeny ratios, formulate testable hypotheses, and use chi-square analysis to initially evaluate their model for one of the two genes. A core innovation is requiring students to design a definitive follow-up cross to resolve remaining allelic ambiguities, making experimental design an explicit objective. Finally, students analyze the results of their proposed test cross, performing a final chi-square test on the complete two-gene system. This module integrates core concepts: two-gene Mendelian inheritance, statistical analysis, and hypothesis-driven design into a cohesive investigative experience. This module allowed students to practice formulating their hypothesis and experimental design. Based on survey responses, most students (~72%) agreed that they learned to apply genetic concepts in the laboratory module.