Wednesday, November 4, 2009
Ballroom A+B (Camino Real Hotel)
Mutations in a variety of genes can give rise to polydactyly. Typically the mutated gene is involved in developmental patterning, and a syndrome of congenital anomalies results, of which polydactyly is one feature. One of such multi-symptom diseases is the Ellis van Creveld (EvC) syndrome. EvC syndrome is a rare human genetic disorder resulting from abnormal bone and muscle development, and is characterized by mild short stature, postaxial polydactyly, dysplastic nail and teeth and heart defects. Genetic studies demonstrated that mutations in a gene known as EVC caused phenotypes that were clinically similar to EvC syndrome. The EVC gene encodes a novel protein with putative transmembrane region, nuclear localization signal and a leucine-zipper structure; otherwise it shares no major similarities with other proteins to give clues to its functions. Recent experiments done using a mouse model suggested that EVC is a regulator of the hedgehog signal transduction pathway that controls the development and growth of bones during embryogenesis. Bioinformatic analysis in our laboratory indicated the presence of an ‘enzymatic’ region in the protein sequence. As a first step towards elucidating the function of the EVC protein, we have successfully cloned the fragment of the EVC gene that encodes the protein product for the putative enzymatic and leucine-zipper regions into bacterial protein expression vectors. We have expressed the protein product and are developing strategies to isolate and purify this fragment to homogeneity for structural and enzymatic studies using X-ray crystallography, NMR, SPR and other spectroscopic techniques. The results of these studies will be presented.