Myotonic dystrophy (DM) is one of the most important hereditary neuromuscular disorders with an autosomal dominant mode of inheritance. The biochemical basis of DM is totally unknown, but linkage studies have been successful in assigning the DM gene to the proximal portion of the long arm of chromosome 19 (19 centromere-q 13.2). However, the precise order and physical distances between the various markers linked to DM is still uncertain and tightly linked flanking markers have not yet been identified. This project aims to use the new technology of pulse field gel electrophoresis to construct a macro-restriction map in the region surrounding the myotonic dystrophy gene. Such mapping is only possible however, if numerous closely spaced probes from the region surrounding the DM gene are available. Since available markers are at considerable distances from each other and the DM gene, new markers will be generated from a flow sorted chromosome 19 library and localized to the 19 centro- mere-q 13.2 region (which carries the DM gene) by in situ hybridization studies. Currently available and newly generated markers will be used as probes in pulse field digests to construct a macro-restriction map of the region and physical maps from normals and myotonic dystrophy patients will be compared to search for chromosomal aberrations such as deletions. This project will result in the generation of new probes close to the DM gene and the construction of detailed physical maps in normals and DM patients which will reveal the precise location and distance of old and new markers relative to the DM gene and each other. This will provide valuable data required for actual physical isolation and identification of the DM gene.
| Bhagavati, S; Bhagwati, S; Ghatpande, A et al. (1996) In situ hybridization analysis for expression of myogenic regulatory factors in regenerating muscle of mdx mouse. J Neuropathol Exp Neurol 55:509-14 |
