| Research Abstract |
Myotonic muscular dystrophy (DM) is an autosomal dominant disorder with an incidence of approximately 5 per 10^5 of the population both in Caucasian countries and Japan. It is characterized by the appearance of features of premature aging in the second or third decade. Striking features include myotonia, muscle wasting, cataract, hypogonadism, frontal balding, and mental retardation mostly. There are no candidate genes for DM so far. Cloning the DM gene will not only be useful for helping us understand the disease processes occurring in DM but will also give us clues to the molecular mechanism underlying aging. It has been reported that the gene responsible for DM is tightly linked to polymorphic DNA markers on the long arm of chromosome 19 (Shaw et al. 1985. : Takemoto et al., 1990).
For the purpose of cloning the gene for DM, we have introduced new methods such as making a NotI linking library, in situ hybridization, PFGE (pulsed field gel electrophoresis) and TGGE (temperature gradient gel electrophoresis). We have isolated 5 NotI linking clones derived from chromosome 19 and 3 of them demonstrated RFLPs. By chromosome in situ suppression hybridization, ERCC2 (DNA repair gene 2) locus has been estimated to map to a position corresponding to 58% (n=31) of the length of 19q distal of the centromere. The ERCC1 (DNA repair gene 1) has been mapped 380kb distal to CKMM (creatine kinase, muscle type) using PFGE. We are currently focusing on generating a detailed physical and genetic map of the region around the DM locus.
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