Abstract
Duchenne muscular dystropy (DMD) is an X-linked disorder affecting about 1 in 3,500 males1,2. It is allelic with the milder Becker muscular dystrophy. The biochemical basis for both diseases is unknown and no effective treatment is available. Long-range physical mapping has shown that the DMD gene, localized in Xp21, is extremely large2–6, exceeding 2 million base pairs7. Until now, carrier detection and prenatal diagnosis has involved the use of linked restriction fragment length polymorphism markers8,9 which detect muscular dystrophy-associated deletions in about 10% of the cases10–12. Field inversion gel electrophoresis (F1GE) allows the detection of structural rearrangements in 21 out of 39 of the DMD patients studied (54%), of which 14 (65%) were not detected by conventional methods. Large deletions seem to make up a much higher fraction of the DMD mutations than so far indicated by other methods. A region prone to deletion was located in the distal half of the gene. FIGE analysis could provide a valuable extension of information for carrier detection and prenatal diagnosis. The technique should be generally applicable to the study of diseases involving structural chromosomal rearrangements.
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den Dunnen, J., Bakker, E., Breteler, E. et al. Direct detection of more than 50% of the Duchenne muscular dystrophy mutations by field inversion gels. Nature 329, 640–642 (1987). https://doi.org/10.1038/329640a0
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DOI: https://doi.org/10.1038/329640a0
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