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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References
Moser, H. Hum. Genet. 66, 17–40 (1984).
Monaco, A. P. & Kunkel, L. M. Trends Genet. 3, 33–37 (1987).
Monaco, A. P. et al. Nature 323, 646–650 (1986).
Burmeister, M. & Lehrach, H. Nature 324, 482–485 (1986).
Van Ommen, G. J. B. et al. Cell 47, 499–504 (1986).
Kenwrick, S., Patterson, M., Speer, A., Fischbeck, K. & Davies, K. Cell 48, 351–357 (1987).
van Ommen, G. J. B. et al. Genomics (submitted).
Wieacker, P., Davies, K. E., Pearson, P. L. & Ropers, H-H. Lancet ii, 1325–1327 (1983).
Bakker, E. et al. Lancet i, 655–658 (1985).
Monaco, A. P. et al. Nature 316, 842–845 (1985).
Kunkel, L. M. et al. Nature 322, 73–77 (1986).
Monaco, A. P., Bertelson, C. J., Colletti-Feener, C. & Kunkel, L. M. Hum. Genet. 75, 221–227 (1987).
Bakker, E. et al. J. med. Genet. 23, 573–580 (1986).
Carle, G. R. & Olson, M. V. Nucleic Acids Res. 12, 5647–5664 (1984).
Carle, G. R., Frank, M. & Olson, M. V. Science 232, 65–68 (1986).
Fischbeck, K. H. et al. Lancet ii, 104 (1986).
Koenig, M. et al. Cell 50, 509–517 (1987).
Burghes, A. H. M. et al. Nature 328, 434–437 (1987).
Ray, P. N. et al. Nature 318, 672–675 (1985).
van Ommen, G. J. B. & Verkerk, J. M. K. in Human Genetic Disease, A Practical Approach (ed. Davies, K. E.) 113–133 (IRL, Oxford, 1986).
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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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