Master of Science
Dr. Peter Rogan
Currently, Molecular Diagnostics Laboratories in Ontario sequence coding and adjacent intronic regions in BRCA1 and BRCA2 in patients with a family history of breast cancer. At LHSC it is estimated that ~15% of patients have BRCA1 or BRCA2 variants of clinical significance, and ~15-20% patients have variants of unknown clinical significance (VUS), while the remaining patients have variants of no clinical significance, making patient prognosis difficult to ascertain. To elucidate VUS and improve deleterious variant detection, my study has three aims, 1) assess the effects of VUS on splicing using bioinformatics and transfection assays; 2) investigate the limitations of BRCA1 and BRCA2 routine sequencing in deleterious variant detection and expand deleterious variant detection by sequencing seven breast cancer associated genes in 21 familial breast cancer patients and 3) prioritize detected variants in silico for effects on: splicing, transcription factor binding, mRNA structure, miRNA binding and amino acids.
Dovigi, Eddie A., "Detection, prioritization and analysis of variants of unknown significance in familial breast cancer genes" (2013). Electronic Thesis and Dissertation Repository. 1633.