The region Xp21 of the human genome will reduced to an ordered array of cloned DNA segments by chromosome """"""""walking"""""""" from multiple start points from within the region. The locus responsible for Duchenne muscular dystrophy known to lie within Xp21 will be identified and the product encoded by this locus characterized. The manner in which the product of the DMD locus is altered in patients will be determined by direct analysis of the DNA of the affected individuals. Mutations which disrupt normal function will be used as indicators of where the normal product from the locus functions. Structural characteristics of the Xp21 region which might affect normal expression from the locus will be studied with special emphasis given to possible mutational instablity of the region. The genetic distance of the entire region will be precisely determined and meiotic exchange points identified. Accurate prediction of individuals at risk for the disease will result by either direct analysis of the locus or indirect analysis with tightly linked markers. Ultimately, the pathways in neuromuscular development will be identified which are altered in Duchenne muscular dystrophy patients and possibly patients with other neuromuscular diseases.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Mammalian Genetics Study Section (MGN)
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Children's Hospital Boston
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