Findings may lead to genetic tests
Researchers at The Hospital for Sick Children (Sick Kids) and Mount Sinai Hospital (MSH) have discovered a possible genetic mechanism behind congenital heart defects. This finding has implications for understanding how congenital heart defects occur, and may lead to genetic tests for certain defects, such as proteins that determine how genes are expressed. This also opens new insights into how general chromosome properties can relate to specific disease processes. This research is reported in the November 4, 2004 issue of the scientific journal Nature. "It was previously believed that all cells during development contained the same chromatin remodelling proteins that unwind DNA, a process that is important for genes to be turned on. However, we identified one of these proteins, called Baf60c, that is expressed specifically in the developing heart," said Dr. Benoit Bruneau, the studys co-principal investigator, a Sick Kids scientist and an assistant professor of Molecular and Medical Genetics at the University of Toronto (U of T). "When we completely suppressed the function of the Baf60c protein, there were dramatic cardiovascular defects. When we suppressed just half of the protein, the result was a defect that resembled one seen in infants," added Dr. Bruneau, also Canada Research Chair in Developmental Cardiology and member of U of Ts Heart & Stroke/Richard Lewar Centre of Excellence.
Using a novel way of reducing gene function called in vitro RNAi, the team developed mouse models with different levels of the protein. They were then able to see the effects of the suppressed protein using optical projection tomography at the Mouse Imaging Centre at Sick Kids. Knockout mice, where a specific gene is replaced, or removed, allow researchers to have precise control over a specific gene in order to study its function. "This new protein may provide new diagnostic tools and insights into how to treat cardiovascular problems," said Dr. Janet Rossant, the studys co-principal investigator and a senior investigator at the Samuel Lunenfeld Research Institute at MSH, as well as a professor of Molecular and Medical Genetics at U of T. Congenital heart defects are among the most prevalent and serious conditions affecting children, occurring in approximately one out of 100 live births in Canada. The next steps for this research involve examining patients with congenital heart defects to see if they, like the mouse model, have this modified protein.
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