Monogenic Mendelian syndromes, although individually rare, constitute a large burden on families and the health care system. Such disorders are caused by rare genetic variants that disrupt protein-coding genes to cause disease. In contrast, common diseases that affect >5% of patients are polygenic, and consist of mostly non-coding variants, most of which do not alter the protein and therefore likely regulate gene expression.

Emerging precision medicine initiatives focus on individualized diagnosis, prognosis and treatment based on the integration of clinical, genomic, epigenetic, and other biomarkers. Our lab seeks to advance these goals in the setting of rare Mendelian syndromes. While precision medicine has been wildly successful in providing genetic diagnoses through clinical whole exome sequencing, it has left in its wake a gap between our expanded diagnostic capability and our ability to provide therapies based on the genetic diagnosis.

The majority of patients now have a genetic diagnosis that ends the “diagnostic odyssey”, but leave clinicians with vexing questions regarding prognosis and treatments based on the genetic diagnosis. Our lab seeks to bridge this gap, leveraging both publically available data for a wide variety of complex disease and functional genomic data generated from samples in patients with rare monogenic disease.