Grant: Foundation Grant

Congenital heart disease (CHD) affects 1-5% of the population and represents the largest class of birth defects. It is the leading cause of death in infants during the first year of life. It is also an independent risk factor for premature onset of adult cardiovascular disease including degenerative valve disease, myocardial infarction and sudden death. It is well established that CHD is a heritable trait, i.e. it 'runs in the family'. However, its transmission does not follow simple Mendelian inheritance and is influenced by other genetic as well as environmental factors. Despite great advances over the past decade, the genes responsible for the majority of human CHD remain unknown. A better understanding of the genes required for normal heart development will immensely advance our understanding and detection of CHD. It will also improve care for individuals with CHD and help prevent cardiovascular complications. During the past decade, our lab has proudly contributed to this area thru our discovery and characterization of several genes essential for normal heart development such as GATA4 and GATA5. Alterations in these genes are associated with several types of human CHD, including bicuspid aortic valve, atrial and ventricular septal defects as well as rhythm abnormalities. Using our unique tools and animal models of human disease, we wish to pursue our studies aimed at understanding the genetics of normal and abnormal heart development. We will also use our animal models to gain a better understanding of how cardiac birth defects make the heart more vulnerable to other cardiovascular problems. Such knowledge will help design therapies for prevention and treatment that are presently unavailable. The results of our research will continue to impact diagnosis and care of individuals with heart disease or with a family history of the disease.