Supervisor: John Parkinson, collorative internship proposed with Fred W. Keely, Department of Biochemisty, University of Toronto.
WiP Seminar, 22 Nov 2011
Elastin polymorphisms associated with increased risk of cardiovascular disease
Elastin, a polymeric protein and a member of extra cellular matrix, is playing a major role in elasticity of many tissues including skin, lung parenchyma and large arteries. It is a major structural protein in the walls of large blood vessels such as aorta and is responsible for elasticity of vascular tissues. Elastin fibers are remarkably stable with little or no normal turnover over the life-span of an individual therefore; they should be able to withstand millions of cycles of extension and recoil in tissues such as arteries without mechanical failure. We hypothesize that any subtle variation in elastin sequence can impact Elastin durability in arteries and consequently increase susceptibility to cardiovascular diseases. Applying the Solexa next generation sequencing platform, we have sequenced the elastin gene (ELN) from 800 subjects diagnosed with thoracic aortic aneurysm and dissection (TAAD) in addition to 400 control samples from Ontario residents. Our goal is to identify and characterize those SNPs in the elastin gene that are enriched in TAAD cohort.
Sequence variants in elastin and their association with late-onset of cardiovascular disease
Elastin, a polymeric protein and a member of extra cellular matrix, is playing a major role in elasticity of many tissues including skin, lung parenchyma and large arteries. It is a major structural protein in the walls of large blood vessels such as aorta and is responsible for elasticity of vascular tissues. Elastic properties of vascular tissues is very important for their physiological function, therefore abnormalities in elastin production or assembly can result in cardiovascular conditions, such as aneurysms, hypertension and atherosclerosis. Better understanding of elastin sequence variability between patients diagnosed with heart disease and healthy individuals and the impact of discovered sequence variants on elastin biomechanical properties and function will have applications in design of novel diagnostics and biomarkers for late-onset of cardiovascular disease.
In my research I plan to 1- Characterize elastin sequence variants in patients diagnosed with late-onset cardiovascular diseases. 2- Explore the impact of sequence variants on elastin biomechanical properties 3- Experimentally validate sequence variants by generating recombinant polypeptides For the first stage of my research, samples from 800 Thoracic Aortic Aneurysm and Dissection (TAAD) patients were collected by Dr. Dianna Milewicz from University of Texas Medical School. These samples were sequenced along with 400 samples from OPGP (Ontario Population Genomic Repository), by The Centre for Applied Genomics (TCAG) at SickKids using next generation sequencing Solexa. For sequence alignment and SNP calling, I used MAQ (Mapping and Assembly with Quality). I also used Perl and R for parsing files created by MAQ and analyzing data. Currently I am in the process of selecting SNPs for genotyping and further study their impact on Elastin integrity and function which will help us increase our understanding of pathologies of late-onset of cardiovascular disease.