Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1995 Jan;56(1):123–130.

Normal variation at the myotonic dystrophy locus in global human populations.

C Zerylnick 1, A Torroni 1, S L Sherman 1, S T Warren 1
PMCID: PMC1801327  PMID: 7825567

Abstract

Myotonic dystrophy (DM) is a dominant neuromuscular disease that results from an unstable CTG-repeat expansion in the 3' UTR of the myotonin kinase gene at 19q13.3. This repeat is normally polymorphic with a trimodal distribution reflecting 5-, 11-17-, and 19-30-repeat-length alleles. An absolute association between expanded CTG alleles and the 1-kb insertion allele of an intragenic polymorphism in Caucasians has led to the proposal that the 5-repeat allele gives rise to alleles of 19-30 repeats, from which expanded alleles are derived, a transition not involving the 11-17-repeat alleles. A survey of eight global populations confirms the stability of the 11-17-repeat alleles but shows disociation between the 1-kb insertion polymorphism and both the 5- and 19-30-repeat-length alleles. These data indicate more than one ancestral allele from which expanded alleles are derived and suggest that widely variable population frequencies of DM may reflect distinct frequencies of such predisposed alleles.

Full text

PDF
123

Images in this article

126Figure 2
on p.126
127Figure 3
on p.127
127Figure 4
on p.127

Selected References

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

  1. Ashizawa T., Epstein H. F. Ethnic distribution of myotonic dystrophy gene. Lancet. 1991 Sep 7;338(8767):642–643. doi: 10.1016/0140-6736(91)90659-d. [DOI] [PubMed] [Google Scholar]
  2. Ballinger S. W., Schurr T. G., Torroni A., Gan Y. Y., Hodge J. A., Hassan K., Chen K. H., Wallace D. C. Southeast Asian mitochondrial DNA analysis reveals genetic continuity of ancient mongoloid migrations. Genetics. 1992 Jan;130(1):139–152. doi: 10.1093/genetics/130.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bouchard G., Roy R., Declos M., Mathieu J., Kouladjian K. Origin and diffusion of the myotonic dystrophy gene in the Saguenay region (Quebec). Can J Neurol Sci. 1989 Feb;16(1):119–122. doi: 10.1017/s0317167100028651. [DOI] [PubMed] [Google Scholar]
  4. Brook J. D., McCurrach M. E., Harley H. G., Buckler A. J., Church D., Aburatani H., Hunter K., Stanton V. P., Thirion J. P., Hudson T. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992 Feb 21;68(4):799–808. doi: 10.1016/0092-8674(92)90154-5. [DOI] [PubMed] [Google Scholar]
  5. Dada T. O. Dystrophia myotonica in a Nigerian family. East Afr Med J. 1973 Apr;50(4):213–228. [PubMed] [Google Scholar]
  6. Dausset J., Cann H., Cohen D., Lathrop M., Lalouel J. M., White R. Centre d'etude du polymorphisme humain (CEPH): collaborative genetic mapping of the human genome. Genomics. 1990 Mar;6(3):575–577. doi: 10.1016/0888-7543(90)90491-c. [DOI] [PubMed] [Google Scholar]
  7. Davies J., Yamagata H., Shelbourne P., Buxton J., Ogihara T., Nokelainen P., Nakagawa M., Williamson R., Johnson K., Miki T. Comparison of the myotonic dystrophy associated CTG repeat in European and Japanese populations. J Med Genet. 1992 Nov;29(11):766–769. doi: 10.1136/jmg.29.11.766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fu Y. H., Pizzuti A., Fenwick R. G., Jr, King J., Rajnarayan S., Dunne P. W., Dubel J., Nasser G. A., Ashizawa T., de Jong P. An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science. 1992 Mar 6;255(5049):1256–1258. doi: 10.1126/science.1546326. [DOI] [PubMed] [Google Scholar]
  9. Goldman A., Ramsay M., Jenkins T. Absence of myotonic dystrophy in southern African Negroids is associated with a significantly lower number of CTG trinucleotide repeats. J Med Genet. 1994 Jan;31(1):37–40. doi: 10.1136/jmg.31.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Imbert G., Kretz C., Johnson K., Mandel J. L. Origin of the expansion mutation in myotonic dystrophy. Nat Genet. 1993 May;4(1):72–76. doi: 10.1038/ng0593-72. [DOI] [PubMed] [Google Scholar]
  11. Jansen G., Bartolomei M., Kalscheuer V., Merkx G., Wormskamp N., Mariman E., Smeets D., Ropers H. H., Wieringa B. No imprinting involved in the expression of DM-kinase mRNAs in mouse and human tissues. Hum Mol Genet. 1993 Aug;2(8):1221–1227. doi: 10.1093/hmg/2.8.1221. [DOI] [PubMed] [Google Scholar]
  12. Knight S. J., Flannery A. V., Hirst M. C., Campbell L., Christodoulou Z., Phelps S. R., Pointon J., Middleton-Price H. R., Barnicoat A., Pembrey M. E. Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Cell. 1993 Jul 16;74(1):127–134. doi: 10.1016/0092-8674(93)90300-f. [DOI] [PubMed] [Google Scholar]
  13. Koide R., Ikeuchi T., Onodera O., Tanaka H., Igarashi S., Endo K., Takahashi H., Kondo R., Ishikawa A., Hayashi T. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nat Genet. 1994 Jan;6(1):9–13. doi: 10.1038/ng0194-9. [DOI] [PubMed] [Google Scholar]
  14. Kunst C. B., Warren S. T. Cryptic and polar variation of the fragile X repeat could result in predisposing normal alleles. Cell. 1994 Jun 17;77(6):853–861. doi: 10.1016/0092-8674(94)90134-1. [DOI] [PubMed] [Google Scholar]
  15. La Spada A. R., Wilson E. M., Lubahn D. B., Harding A. E., Fischbeck K. H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature. 1991 Jul 4;352(6330):77–79. doi: 10.1038/352077a0. [DOI] [PubMed] [Google Scholar]
  16. Lavedan C., Hofmann-Radvanyi H., Boileau C., Bonaïti-Pellié C., Savoy D., Shelbourne P., Duros C., Rabes J. P., Dehaupas I., Luce S. French myotonic dystrophy families show expansion of a CTG repeat in complete linkage disequilibrium with an intragenic 1 kb insertion. J Med Genet. 1994 Jan;31(1):33–36. doi: 10.1136/jmg.31.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mahadevan M. S., Foitzik M. A., Surh L. C., Korneluk R. G. Characterization and polymerase chain reaction (PCR) detection of an Alu deletion polymorphism in total linkage disequilibrium with myotonic dystrophy. Genomics. 1993 Feb;15(2):446–448. doi: 10.1006/geno.1993.1087. [DOI] [PubMed] [Google Scholar]
  18. Mahadevan M., Tsilfidis C., Sabourin L., Shutler G., Amemiya C., Jansen G., Neville C., Narang M., Barceló J., O'Hoy K. Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. Science. 1992 Mar 6;255(5049):1253–1255. doi: 10.1126/science.1546325. [DOI] [PubMed] [Google Scholar]
  19. Neville C. E., Mahadevan M. S., Barceló J. M., Korneluk R. G. High resolution genetic analysis suggests one ancestral predisposing haplotype for the origin of the myotonic dystrophy mutation. Hum Mol Genet. 1994 Jan;3(1):45–51. doi: 10.1093/hmg/3.1.45. [DOI] [PubMed] [Google Scholar]
  20. Orr H. T., Chung M. Y., Banfi S., Kwiatkowski T. J., Jr, Servadio A., Beaudet A. L., McCall A. E., Duvick L. A., Ranum L. P., Zoghbi H. Y. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet. 1993 Jul;4(3):221–226. doi: 10.1038/ng0793-221. [DOI] [PubMed] [Google Scholar]
  21. Osame M., Furusho T. [Genetic epidemiology of myotonic dystrophy in Kagoshima and Okinawa districts in Japan]. Rinsho Shinkeigaku. 1983 Dec;23(12):1067–1071. [PubMed] [Google Scholar]
  22. Sabouri L. A., Mahadevan M. S., Narang M., Lee D. S., Surh L. C., Korneluk R. G. Effect of the myotonic dystrophy (DM) mutation on mRNA levels of the DM gene. Nat Genet. 1993 Jul;4(3):233–238. doi: 10.1038/ng0793-233. [DOI] [PubMed] [Google Scholar]
  23. Scozzari R., Torroni A., Semino O., Sirugo G., Brega A., Santachiara-Benerecetti A. S. Genetic studies on the Senegal population. I. Mitochondrial DNA polymorphisms. Am J Hum Genet. 1988 Oct;43(4):534–544. [PMC free article] [PubMed] [Google Scholar]
  24. Shaw D. J., McCurrach M., Rundle S. A., Harley H. G., Crow S. R., Sohn R., Thirion J. P., Hamshere M. G., Buckler A. J., Harper P. S. Genomic organization and transcriptional units at the myotonic dystrophy locus. Genomics. 1993 Dec;18(3):673–679. doi: 10.1016/s0888-7543(05)80372-6. [DOI] [PubMed] [Google Scholar]
  25. Smeets H. J., Hermens R., Brunner H. G., Ropers H. H., Wieringa B. Identification of variable simple sequence motifs in 19q13.2-qter: markers for the myotonic dystrophy locus. Genomics. 1991 Feb;9(2):257–263. doi: 10.1016/0888-7543(91)90250-i. [DOI] [PubMed] [Google Scholar]
  26. Torroni A., Chen Y. S., Semino O., Santachiara-Beneceretti A. S., Scott C. R., Lott M. T., Winter M., Wallace D. C. mtDNA and Y-chromosome polymorphisms in four Native American populations from southern Mexico. Am J Hum Genet. 1994 Feb;54(2):303–318. [PMC free article] [PubMed] [Google Scholar]
  27. Torroni A., Miller J. A., Moore L. G., Zamudio S., Zhuang J., Droma T., Wallace D. C. Mitochondrial DNA analysis in Tibet: implications for the origin of the Tibetan population and its adaptation to high altitude. Am J Phys Anthropol. 1994 Feb;93(2):189–199. doi: 10.1002/ajpa.1330930204. [DOI] [PubMed] [Google Scholar]
  28. Torroni A., Schurr T. G., Cabell M. F., Brown M. D., Neel J. V., Larsen M., Smith D. G., Vullo C. M., Wallace D. C. Asian affinities and continental radiation of the four founding Native American mtDNAs. Am J Hum Genet. 1993 Sep;53(3):563–590. [PMC free article] [PubMed] [Google Scholar]
  29. Torroni A., Schurr T. G., Yang C. C., Szathmary E. J., Williams R. C., Schanfield M. S., Troup G. A., Knowler W. C., Lawrence D. N., Weiss K. M. Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations. Genetics. 1992 Jan;130(1):153–162. doi: 10.1093/genetics/130.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tsilfidis C., MacKenzie A. E., Mettler G., Barceló J., Korneluk R. G. Correlation between CTG trinucleotide repeat length and frequency of severe congenital myotonic dystrophy. Nat Genet. 1992 Jun;1(3):192–195. doi: 10.1038/ng0692-192. [DOI] [PubMed] [Google Scholar]
  31. Verkerk A. J., Pieretti M., Sutcliffe J. S., Fu Y. H., Kuhl D. P., Pizzuti A., Reiner O., Richards S., Victoria M. F., Zhang F. P. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell. 1991 May 31;65(5):905–914. doi: 10.1016/0092-8674(91)90397-h. [DOI] [PubMed] [Google Scholar]
  32. Wallace D. C., Torroni A. American Indian prehistory as written in the mitochondrial DNA: a review. Hum Biol. 1992 Jun;64(3):403–416. [PubMed] [Google Scholar]

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

RESOURCES