The Seidman laboratory uses genetic techniques to study the molecular basis of inherited human disorders. A central project in the laboratory has been to understand the genetic basis of inherited cardiovascular diseases. Genetic work on Familial Hypertrophic Cardiomyopathy (FHC) has demonstrated disease-causing mutations in genes encoding sarcomere proteins: ß cardiac myosin heavy chain (MHC), a tropomyosin, cardiac troponin T or myosin binding protein-C. Increasingly genotype data is providing important clinical information to patients and physicians. Genetic etiologies help to explain why some mutations result in late-onset cardiac hypertrophy, whereas others predispose one to early disease and sudden death. Murine models (produced via embryonic stem cell technologies) have been developed to study how these gene mutations produce these different phenotypes and help to investigate the role of modifying genes and environment in disease expression.

A molecular genetic approach is also used to study dilated cardiomyopathies. Several loci have been identified and most recently a disease gene has been identified that causes conduction system disease in advance of ventricular dysfunction. Similarly we have use genetic approaches to study congenital heart disease and recently have demonstrated that transcription factor gene mutations account for Holt-Oram syndrome (TBX5 defects) and atrial septal defects associated with conduction system disease (Nkx2-5). Work is underway to determine if other genes that pattern the heart during embryogenesis are mutated in other congenital heart defects.