Medical Sciences Commons^™

Detection, Prioritization And Analysis Of Variants Of Unknown Significance In Familial Breast Cancer Genes, Eddie A. Dovigi

Electronic Thesis and Dissertation Repository

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 …

Pharmacogenetics Of Oral Anticoagulants And Antiplatelets, Inna Gong

Electronic Thesis and Dissertation Repository

Thromboembolic disorders are a major cause of morbidity and mortality. Therapeutic intervention with anticoagulants and antiplatelets greatly reduces the risk of arterial and venous thrombosis. However, the observed large interindividual variation in responsiveness to these drugs indicates that subsets of patients are not attaining optimal therapy, resulting in either lack of antithrombotic effect or elevated bleeding risk. Recently, single nucleotide polymorphisms (SNPs) have been linked to the variation observed in efficacy and toxicity for many cardiovascular drugs.

Warfarin has been the gold standard anticoagulant for prevention of stroke and thromboembolism in atrial fibrillation (AF) and venous thromboembolism (VTE) patients. SNPs …

Systematic Assessment Of The Contribution Of Superantigens To Nasopharyngeal Colonization In A Mouse Model Of Streptococcal Infection, Katherine J. Kasper

Electronic Thesis and Dissertation Repository

Streptococcus pyogenes is adapted for persistence in humans. It typically colonizes the tonsils and skin, and humans are the only known reservoir. S. pyogenes can cause a wide range of mild to serious infections. Most streptococci-related deaths are due to complications of rheumatic fever and invasive infections. S. pyogenes produces virulence factors that contribute to the pathogen’s ability to colonize and cause disease, including streptococcal superantigens (SAgs), also known as streptococcal pyrogenic exotoxins (Spes). SAgs function by cross-linking T cells and antigen presenting cells (APC) which may cause a massive inflammatory response, and as such have been found to contribute …