Mendelian or Multifactorial? Current Undergraduate Genetics Assessments Focus on Genes and Rarely Include the Environment.

Undergraduate genetics courses have historically focused on simple genetic models, rather than taking a more multifactorial approach where students explore how traits are influenced by a combination of genes, the environment, and gene-by-environment interactions. While a focus on simple genetic models can provide straightforward examples to promote student learning, they do not match the current scientific understanding and can result in deterministic thinking among students. In addition, undergraduates are often interested in complex human traits that are influenced by the environment, and national curriculum standards include learning objectives that focus on multifactorial concepts. This research aims to discover to what extent multifactorial genetics is currently being assessed in undergraduate genetics courses. To address this, we analyzed over 1,000 assessment questions from a commonly used undergraduate genetics textbook; published concept assessments; and open-source, peer-reviewed curriculum materials. Our findings show that current genetics assessment questions overwhelmingly emphasize the impact of genes on phenotypes and that the effect of the environment is rarely addressed. These results indicate a need for the inclusion of more multifactorial genetics concepts, and we suggest ways to introduce them into undergraduate courses.

A Novel Pathway that Links Caveolin-1 Down-Regulation to BRCA1 Dysfunction in Serous Epithelial Ovarian Cancer Cells.

Ovarian cancer is the second most common gynecological cancer and the five-year survival rate is only about 40%. High-grade serous carcinoma is the pre-dominant histotype associated with hereditary ovarian cancer and women with inherited mutations in BRCA1 have a lifetime risk of 40-60%. BRCA1 and its isoform BRCA1a are multifunctional proteins that are the most evolutionary conserved of all the other splice variants. Our group has previously reported that BRCA1/1a proteins, unlike K109R and C61G mutants, suppress growth of ovarian cancer cells by tethering Ubc9. In this study we found wild type BRCA1/1a proteins to induce expression of caveolin-1, a tumor suppressor in BRCA1-mutant serous epithelial ovarian cancer (SEOC) cells by immunofluorescence analysis. The K109R and C61G disease associated mutant BRCA1 proteins that do not bind Ubc9 were not as efficient in up-regulation of caveolin-1 expression in SEOC cells. Additionally, immunofluorescence analysis showed BRCA1/1a proteins to induce redistribution of Caveolin-1 from cytoplasm and nucleus to the cell membrane. This is the first study demonstrating the physiological link between loss of Ubc9 binding, loss of growth suppression and loss of Caveolin-1 induction of disease-associated mutant BRCA1 proteins in SEOC cells. Decreased Caveolin-1 expression combined with elevated Ubc9 expression can in the future be used as an early biomarker for BRCA1 mutant SEOC.