Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1990 Jun;46(6):1073–1081.

A new polymorphic probe which defines the region of chromosome 19 containing the myotonic dystrophy locus

K Johnson, P Shelbourne, J Davies, J Buxton, E Nimmo, M J Siciliano, L L Bachinski, M Anvret, H Harley, S Rundle, T Miki, H Brunner, R Williamson
PMCID: PMC1683833  PMID: 1971149

Abstract

The region of human chromosome 19 which includes the myotonic dystrophy locus (DM) has recently been redefined by the tight linkage between it and the gene for muscle-specific creatine kinase (CKMM), which lies just proximal to DM. Utilizing human/hamster hybrid cell lines containing defined breakpoints within this region, we have assigned a number of new probes close to DM. Two of these probes, p134B and p134C, were isolated from a single cosmid clone (D19S51) and detect the same BglI RFLP; p134C detects an additional RFLP with the enzyme PstI. Analysis of these probes in the Centre d'Etude du Polymorphisme Humain families demonstrates tight linkage with a number of markers known to be proximal to DM. A two-point lod score of 6.34 at θ = .025 demonstrates the linkage of this probe to DM. Analysis of a DM individual previously shown to be recombinant for other tightly linked markers indicates that p134C is distal to DM. This result indicates that both the new probe and the existing group of proximal probes including CKMM and ERCC1 probably flank DM and define the genetic interval into which this mutation maps.

Full text

PDF

Images in this article

1077Figure 3
on p.1077
1078Figure 4
on p.1078

Selected References

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

  1. Bartlett R. J., Pericak-Vance M. A., Yamaoka L., Gilbert J., Herbstreith M., Hung W. Y., Lee J. E., Mohandas T., Bruns G., Laberge C. A new probe for the diagnosis of myotonic muscular dystrophy. Science. 1987 Mar 27;235(4796):1648–1650. doi: 10.1126/science.3029876. [DOI] [PubMed] [Google Scholar]
  2. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brook J. D., Shaw D. J., Thomas N. S., Meredith A. L., Cowell J., Harper P. S. Mapping genetic markers on human chromosome 19 using subchromosomal fragments in somatic cell hybrids. Cytogenet Cell Genet. 1986;41(1):30–37. doi: 10.1159/000132192. [DOI] [PubMed] [Google Scholar]
  4. Brunner H. G., Korneluk R. G., Coerwinkel-Driessen M., MacKenzie A., Smeets H., Lambermon H. M., van Oost B. A., Wieringa B., Ropers H. H. Myotonic dystrophy is closely linked to the gene for muscle-type creatine kinase (CKMM). Hum Genet. 1989 Mar;81(4):308–310. doi: 10.1007/BF00283680. [DOI] [PubMed] [Google Scholar]
  5. Brunner H. G., Smeets H., Lambermon H. M., Coerwinkel-Driessen M., van Oost B. A., Wieringa B., Ropers H. H. A multipoint linkage map around the locus for myotonic dystrophy on chromosome 19. Genomics. 1989 Oct;5(3):589–595. doi: 10.1016/0888-7543(89)90027-x. [DOI] [PubMed] [Google Scholar]
  6. Coerwinkel-Driessen M., Schepens J., van Zandvoort P., van Oost B., Mariman E., Wieringa B. NcoI RFLP at the creatine kinase-muscle type gene locus (CKMM, chromosome 19). Nucleic Acids Res. 1988 Sep 12;16(17):8743–8743. doi: 10.1093/nar/16.17.8743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Frossard P. M., Coleman R. T., Assmann G. NcoI RFLP at the human apolipoprotein CII gene locus. Nucleic Acids Res. 1986 Jun 25;14(12):5120–5120. doi: 10.1093/nar/14.12.5120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Frossard P. M., Coleman R. T., Funke H., Assmann G. Dimorphic markers for the human apolipoprotein CII gene locus. Gene. 1987;51(1):103–106. doi: 10.1016/0378-1119(87)90480-x. [DOI] [PubMed] [Google Scholar]
  10. Gibson T. J., Rosenthal A., Waterston R. H. Lorist6, a cosmid vector with BamHI, NotI, ScaI and HindIII cloning sites and altered neomycin phosphotransferase gene expression. Gene. 1987;53(2-3):283–286. doi: 10.1016/0378-1119(87)90017-5. [DOI] [PubMed] [Google Scholar]
  11. Griggs R. C., Wood D. S. Criteria for establishing the validity of genetic recombination in myotonic dystrophy. Neurology. 1989 Mar;39(3):420–421. doi: 10.1212/wnl.39.3.420. [DOI] [PubMed] [Google Scholar]
  12. Hulsebos T., Wieringa B., Hochstenbach R., Smeets D., Schepens J., Oerlemans F., Zimmer J., Ropers H. H. Toward early diagnosis of myotonic dystrophy: construction and characterization of a somatic cell hybrid with a single human der(19) chromosome. Cytogenet Cell Genet. 1986;43(1-2):47–56. doi: 10.1159/000132297. [DOI] [PubMed] [Google Scholar]
  13. Humphries S. E., Jowett N. I., Williams L., Rees A., Vella M., Kessling A., Myklebost O., Lydon A., Seed M., Galton D. J. A DNA polymorphism adjacent to the human apolipoprotein CII gene. Mol Biol Med. 1983 Dec;1(5):463–471. [PubMed] [Google Scholar]
  14. Johnson K. J., Jones P. J., Spurr N., Nimmo E., Davies J., Creed H., Weiss M., Williamson R. Linkage relationships of the protein kinase C gamma gene which exclude it as a candidate for myotonic dystrophy. Cytogenet Cell Genet. 1988;48(1):13–15. doi: 10.1159/000132577. [DOI] [PubMed] [Google Scholar]
  15. Johnson K., Shelbourne P., Davies J., Buxton J., Nimmo E., Anvret M., Bonduelle M., Williamson B., Savontaus M. L. Recombination events that locate myotonic dystrophy distal to APOC2 on 19q. Genomics. 1989 Nov;5(4):746–751. doi: 10.1016/0888-7543(89)90116-x. [DOI] [PubMed] [Google Scholar]
  16. Korneluk R. G., MacKenzie A. E., Nakamura Y., Dubé I., Jacob P., Hunter A. G. A reordering of human chromosome 19 long-arm DNA markers and identification of markers flanking the myotonic dystrophy locus. Genomics. 1989 Oct;5(3):596–604. doi: 10.1016/0888-7543(89)90028-1. [DOI] [PubMed] [Google Scholar]
  17. Korneluk R. G., MacLeod H. L., McKeithan T. W., Brooks J. D., MacKenzie A. E. A chromosome 19 clone from a translocation breakpoint shows close linkage and linkage disequilibrium with myotonic dystrophy. Genomics. 1989 Feb;4(2):146–151. doi: 10.1016/0888-7543(89)90293-0. [DOI] [PubMed] [Google Scholar]
  18. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Le Beau M. M., Ryan D., Jr, Pericak-Vance M. A. Report of the committee on the genetic constitution of chromosomes 18 and 19. Cytogenet Cell Genet. 1989;51(1-4):338–357. doi: 10.1159/000132798. [DOI] [PubMed] [Google Scholar]
  20. Little P. F., Cross S. H. A cosmid vector that facilitates restriction enzyme mapping. Proc Natl Acad Sci U S A. 1985 May;82(10):3159–3163. doi: 10.1073/pnas.82.10.3159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McKeithan T. W., Rowley J. D., Shows T. B., Diaz M. O. Cloning of the chromosome translocation breakpoint junction of the t(14;19) in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9257–9260. doi: 10.1073/pnas.84.24.9257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Meredith A. L., Huson S. M., Lunt P. W., Sarfarazi M., Harley H. G., Brook J. D., Shaw D. J., Harper P. S. Application of a closely linked polymorphism of restriction fragment length to counselling and prenatal testing in families with myotonic dystrophy. Br Med J (Clin Res Ed) 1986 Nov 22;293(6558):1353–1356. doi: 10.1136/bmj.293.6558.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nakamura Y., Lathrop M., O'Connell P., Leppert M., Lalouel J. M., White R. A primary map of ten DNA markers and two serological markers for human chromosome 19. Genomics. 1988 Jul;3(1):67–71. doi: 10.1016/0888-7543(88)90161-9. [DOI] [PubMed] [Google Scholar]
  24. Pericak-Vance M. A., Yamaoka L. H., Assinder R. I., Hung W. Y., Bartlett R. J., Stajich J. M., Gaskell P. C., Ross D. A., Sherman S., Fey G. H. Tight linkage of apolipoprotein C2 to myotonic dystrophy on chromosome 19. Neurology. 1986 Nov;36(11):1418–1423. doi: 10.1212/wnl.36.11.1418. [DOI] [PubMed] [Google Scholar]
  25. Perryman M. B., Hejtmancik J. F., Ashizawa T., Armstrong R., Lin S. C., Roberts R., Epstein H. F. NcoI and TaqI RFLPs for human M creatine kinase (CKM) Nucleic Acids Res. 1988 Sep 12;16(17):8744–8744. doi: 10.1093/nar/16.17.8744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Renaud J. F. Involvement of cation transporting systems in myotonic diseases. Biochimie. 1987 Apr;69(4):407–410. doi: 10.1016/0300-9084(87)90032-0. [DOI] [PubMed] [Google Scholar]
  27. Schonk D., Coerwinkel-Driessen M., van Dalen I., Oerlemans F., Smeets B., Schepens J., Hulsebos T., Cockburn D., Boyd Y., Davis M. Definition of subchromosomal intervals around the myotonic dystrophy gene region at 19q. Genomics. 1989 Apr;4(3):384–396. doi: 10.1016/0888-7543(89)90346-7. [DOI] [PubMed] [Google Scholar]
  28. Sealey P. G., Whittaker P. A., Southern E. M. Removal of repeated sequences from hybridisation probes. Nucleic Acids Res. 1985 Mar 25;13(6):1905–1922. doi: 10.1093/nar/13.6.1905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shaw D. J., Harley H. G., Brook J. D., McKeithan T. W. Long-range restriction map of a region of human chromosome 19 containing the apolipoprotein genes, a CLL-associated translocation breakpoint, and two polymorphic MluI sites. Hum Genet. 1989 Aug;83(1):71–74. doi: 10.1007/BF00274152. [DOI] [PubMed] [Google Scholar]
  30. Shaw D. J., Meredith A. L., Sarfarazi M., Huson S. M., Brook J. D., Myklebost O., Harper P. S. The apolipoprotein CII gene: subchromosomal localisation and linkage to the myotonic dystrophy locus. Hum Genet. 1985;70(3):271–273. doi: 10.1007/BF00273455. [DOI] [PubMed] [Google Scholar]
  31. Smeets H., Bachinski L., Coerwinkel M., Schepens J., Hoeijmakers J., van Duin M., Grzeschik K. H., Weber C. A., de Jong P., Siciliano M. J. A long-range restriction map of the human chromosome 19q13 region: close physical linkage between CKMM and the ERCC1 and ERCC2 genes. Am J Hum Genet. 1990 Mar;46(3):492–501. [PMC free article] [PubMed] [Google Scholar]
  32. Stallings R. L., Olson E., Strauss A. W., Thompson L. H., Bachinski L. L., Siciliano M. J. Human creatine kinase genes on chromosomes 15 and 19, and proximity of the gene for the muscle form to the genes for apolipoprotein C2 and excision repair. Am J Hum Genet. 1988 Aug;43(2):144–151. [PMC free article] [PubMed] [Google Scholar]
  33. Takemoto Y., Miki T., Nishikawa K., Nakura J., Kamino K., Takai S., Honjo T., Ogihara T. The locus for Japanese myotonic dystrophy is also linked to D19S19 on the long arm of chromosome 19. Genomics. 1990 Jan;6(1):195–196. doi: 10.1016/0888-7543(90)90468-a. [DOI] [PubMed] [Google Scholar]
  34. Thompson L. H., Bachinski L. L., Stallings R. L., Dolf G., Weber C. A., Westerveld A., Siciliano M. J. Complementation of repair gene mutations on the hemizygous chromosome 9 in CHO: a third repair gene on human chromosome 19. Genomics. 1989 Nov;5(4):670–679. doi: 10.1016/0888-7543(89)90107-9. [DOI] [PubMed] [Google Scholar]
  35. Todorov A., Jéquier M., Klein D., Morton N. E. Analyse de la ségrégation dans la dystrophie myotonique. J Genet Hum. 1970 Dec;18(4):387–406. [PubMed] [Google Scholar]
  36. Wallis S. C., Donald J. A., Forrest L. A., Williamson R., Humphries S. E. The isolation of a genomic clone containing the apolipoprotein CII gene and the detection of linkage disequilibrium between two common DNA polymorphisms around the gene. Hum Genet. 1984;68(4):286–289. doi: 10.1007/BF00292585. [DOI] [PubMed] [Google Scholar]
  37. Whitehead A. S., Solomon E., Chambers S., Bodmer W. F., Povey S., Fey G. Assignment of the structural gene for the third component of human complement to chromosome 19. Proc Natl Acad Sci U S A. 1982 Aug;79(16):5021–5025. doi: 10.1073/pnas.79.16.5021. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES