Presenting Author:

Bridget Biersmith, Ph.D.

Principal Investigator:

Elizabeth McNally

Department:

Medicine

Keywords:

Cardiomyopathy, Drosophila, heart, Bag3, Ant2

Location:

Third Floor, Feinberg Pavilion, Northwestern Memorial Hospital

B40 - Basic Science

Bolstering Genetic Contributions to Heart Disease Using Drosophila melanogaster

For about two decades, cardiologists have been utilizing genetic panels to establish if patients are at risk for cardiomyopathies. Unfortunately, in vivo analysis of many of these candidates is lacking. In order to ascertain the cardiac function of these genetic variants, we have compiled a list of Drosophila orthologs. These were established using available algorithms, which base homology off of many factors, including DNA sequence, phylogeny, and protein function. Moreover, we used data from whole-genome sequencing of patients with dilated cardiomyopathy to understand if mutations in novel genes could be contributing to defective heart function. Using cardiac-specific RNAi knockdown of these genes and subsequent Drosophila adult heart dissections, we were able to assay cardiac function. We found preliminary evidence showing the conservation of these candidates in heart activity. Specifically, the Bcl2-Associated Athanogene 3 (BAG3) ortholog, Starvin (Stv), presents a shortened systolic diameter and lower fractional shortening when compared to age-matched controls, consistent with a hypercontractility phenotype. To go along with this, a potential candidate from patient sequencing data, the Adenine Nucleotide Translocator 2 (SLC25A5/Ant2; Drosophila Ant2), also presented a hypercontractility phenotype along with a decreased average heart rate and higher fractional shortening. These results exemplify the power of Drosophila melanogaster genetics to study human disease. Our future plans include rescuing these heart defects with the human gene to clarify functional homology and potential in vivo analysis of human variants.