Vertebrate Limb Development 2

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Abnormalities in normal heart formation are the most common birth defect, occurring in 1 in 120 live births. If uncorrected, these defects can have serious debilitating effects on quality of life and in severe cases lead to premature death. Other less life-threatening birth defects also dramatically decrease quality of life in affected individuals. Among these, limb defects are the most common. We are interested in studying the causes of two human syndromes that lead to serious abnormalities in normal heart and limb formation. Patients with Holt-Oram Syndrome (HOS) have severely malformed hearts and limbs and those with Ulnar-Mammary Syndrome (UMS) are afflicted with abnormal limb and mammary gland development.|In each syndrome the corruption of the genetic information in a single gene is sufficient to cause all of the associated abnormalities. Armed with this knowledge of the exact genetic cause of each syndrome we propose to investigate the underlying biology of these diseases. Using the mouse and chicken, we are generating syndrome models that provide a powerful method to understand how loss of normal gene function leads to the disruption of heart and limb formation. In both animal models, the development of the heart and limbs occurs in a similar manner to our own and each animal model has experimental advantages we can exploit. Understanding the genesis of these syndromes will provide information vital in order to devise more effective diagnostic and corrective treatments in human patients.