From genetics to cellular function using computational biology.
This article illustrates how computational biology (computer modeling) can be used to link genetic mutations to their cellular phenotypes. Examples are provided from ion channel defects that are associated with hereditary cardiac arrhythmias--that is, the long QT and Brugada syndromes. State-specific Markov models of wild-type and mutant channels are formulated and introduced into a computer model of the ventricular cardiac cell. Simulations are conducted to study the rate-dependent alterations in action potential properties caused by the mutations. Results provide insights into the cellular mechanisms of QT-interval prolongation on the ECG in the long QT syndrome and of ST-segment elevation in the right precordial leads in the Brugada syndrome.
Rudy
Yoram
Y
Cardiac Bioelectricity Center, 509 Wickenden Building, Case Western Reserve University, Cleveland, OH 44106-7207, USA. yxr@po.cwru.edu
D019295:Computational Biology; D004562:Electrocardiography; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics / Q000503:physiopathology*; D009154:Mutation; D013577:Syndrome