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. 1987 Nov;6(11):3277–3283. doi: 10.1002/j.1460-2075.1987.tb02646.x

Deletions of fetal and adult muscle cDNA in Duchenne and Becker muscular dystrophy patients.

G S Cross 1, A Speer 1, A Rosenthal 1, S M Forrest 1, T J Smith 1, Y Edwards 1, T Flint 1, D Hill 1, K E Davies 1
PMCID: PMC553780  PMID: 3428261

Abstract

We have isolated a cDNA molecule from a human adult muscle cDNA library which is deleted in several Duchenne muscular dystrophy patients. Patient deletions have been used to map the exons across the Xp21 region of the short arm of the X chromosome. We demonstrate that a very mildly affected 61 year old patient is deleted for at least nine exons of the adult cDNA. We find no evidence for differential exon usage between adult and fetal muscle in this region of the gene. There must therefore be less essential domains of the protein structure which can be removed without complete loss of function. The sequence of 2.0 kb of the adult cDNA shows no homology to any previously described protein listed in the data banks although sequence comparison at the amino acid level suggests that the protein has a structure not dissimilar to rod structures of cytoskeletal proteins such as lamin and myosin. There are single nucleotide differences in the DNA sequence between the adult and fetal cDNAs which result in amino acid changes but none that would be predicted to change the structure of the protein dramatically.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Burmeister M., Lehrach H. Long-range restriction map around the Duchenne muscular dystrophy gene. Nature. 1986 Dec 11;324(6097):582–585. doi: 10.1038/324582a0. [DOI] [PubMed] [Google Scholar]
  2. Chen E. Y., Seeburg P. H. Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985 Apr;4(2):165–170. doi: 10.1089/dna.1985.4.165. [DOI] [PubMed] [Google Scholar]
  3. Davies K. E., Pearson P. L., Harper P. S., Murray J. M., O'Brien T., Sarfarazi M., Williamson R. Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome. Nucleic Acids Res. 1983 Apr 25;11(8):2303–2312. doi: 10.1093/nar/11.8.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  5. Fisher D. Z., Chaudhary N., Blobel G. cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6450–6454. doi: 10.1073/pnas.83.17.6450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hart K. A., Hodgson S., Walker A., Cole C. G., Johnson L., Dubowitz V., Bobrow M. DNA deletions in mild and severe Becker muscular dystrophy. Hum Genet. 1987 Mar;75(3):281–285. doi: 10.1007/BF00281075. [DOI] [PubMed] [Google Scholar]
  7. Kenwrick S., Patterson M., Speer A., Fischbeck K., Davies K. Molecular analysis of the Duchenne muscular dystrophy region using pulsed field gel electrophoresis. Cell. 1987 Jan 30;48(2):351–357. doi: 10.1016/0092-8674(87)90438-7. [DOI] [PubMed] [Google Scholar]
  8. Kingston H. M., Sarfarazi M., Thomas N. S., Harper P. S. Localisation of the Becker muscular dystrophy gene on the short arm of the X chromosome by linkage to cloned DNA sequences. Hum Genet. 1984;67(1):6–17. doi: 10.1007/BF00270551. [DOI] [PubMed] [Google Scholar]
  9. Kingston H. M., Thomas N. S., Pearson P. L., Sarfarazi M., Harper P. S. Genetic linkage between Becker muscular dystrophy and a polymorphic DNA sequence on the short arm of the X chromosome. J Med Genet. 1983 Aug;20(4):255–258. doi: 10.1136/jmg.20.4.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kunkel L. M., Hejtmancik J. F., Caskey C. T., Speer A., Monaco A. P., Middlesworth W., Colletti C. A., Bertelson C., Müller U., Bresnan M. Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy. Nature. 1986 Jul 3;322(6074):73–77. doi: 10.1038/322073a0. [DOI] [PubMed] [Google Scholar]
  11. Lindenbaum R. H., Clarke G., Patel C., Moncrieff M., Hughes J. T. Muscular dystrophy in an X; 1 translocation female suggests that Duchenne locus is on X chromosome short arm. J Med Genet. 1979 Oct;16(5):389–392. doi: 10.1136/jmg.16.5.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
  13. Lloyd J. C., Isenberg H., Hopkinson D. A., Edwards Y. H. Isolation of a cDNA clone for the human muscle specific carbonic anhydrase, CAIII. Ann Hum Genet. 1985 Jul;49(Pt 3):241–251. doi: 10.1111/j.1469-1809.1985.tb01698.x. [DOI] [PubMed] [Google Scholar]
  14. Mahdavi V., Periasamy M., Nadal-Ginard B. Molecular characterization of two myosin heavy chain genes expressed in the adult heart. Nature. 1982 Jun 24;297(5868):659–664. doi: 10.1038/297659a0. [DOI] [PubMed] [Google Scholar]
  15. Monaco A. P., Neve R. L., Colletti-Feener C., Bertelson C. J., Kurnit D. M., Kunkel L. M. Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature. 1986 Oct 16;323(6089):646–650. doi: 10.1038/323646a0. [DOI] [PubMed] [Google Scholar]
  16. Murray J. M., Davies K. E., Harper P. S., Meredith L., Mueller C. R., Williamson R. Linkage relationship of a cloned DNA sequence on the short arm of the X chromosome to Duchenne muscular dystrophy. Nature. 1982 Nov 4;300(5887):69–71. doi: 10.1038/300069a0. [DOI] [PubMed] [Google Scholar]
  17. Ray P. N., Belfall B., Duff C., Logan C., Kean V., Thompson M. W., Sylvester J. E., Gorski J. L., Schmickel R. D., Worton R. G. Cloning of the breakpoint of an X;21 translocation associated with Duchenne muscular dystrophy. Nature. 1985 Dec 19;318(6047):672–675. doi: 10.1038/318672a0. [DOI] [PubMed] [Google Scholar]
  18. Sanchez-Pescador R., Urdea M. S. Use of unpurified synthetic deoxynucleotide primers for rapid dideoxynucleotide chain termination sequencing. DNA. 1984 Aug;3(4):339–343. doi: 10.1089/dna.1.1984.3.339. [DOI] [PubMed] [Google Scholar]
  19. Smith T. J., Wilson L., Kenwrick S. J., Forrest S. M., Speer A., Coutelle C., Davies K. E. Isolation of a conserved sequence deleted in Duchenne muscular dystrophy patients. Nucleic Acids Res. 1987 Mar 11;15(5):2167–2174. doi: 10.1093/nar/15.5.2167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  21. Wilcox D. E., Cooke A., Colgan J., Boyd E., Aitken D. A., Sinclair L., Glasgow L., Stephenson J. B., Ferguson-Smith M. A. Duchenne muscular dystrophy due to familial Xp21 deletion detectable by DNA analysis and flow cytometry. Hum Genet. 1986 Jun;73(2):175–180. doi: 10.1007/BF00291610. [DOI] [PubMed] [Google Scholar]
  22. Wood D. S., Zeviani M., Prelle A., Bonilla E., Salviati G., Miranda A. F., DiMauro S., Rowland L. P. Is nebulin the defective gene product in Duchenne muscular dystrophy? N Engl J Med. 1987 Jan 8;316(2):107–108. [PubMed] [Google Scholar]
  23. van Ommen G. J., Verkerk J. M., Hofker M. H., Monaco A. P., Kunkel L. M., Ray P., Worton R., Wieringa B., Bakker E., Pearson P. L. A physical map of 4 million bp around the Duchenne muscular dystrophy gene on the human X-chromosome. Cell. 1986 Nov 21;47(4):499–504. doi: 10.1016/0092-8674(86)90614-8. [DOI] [PubMed] [Google Scholar]

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