Abstract
We have studied linkage disequilibrium between CTG repeats and anAlu insertion/deletion polymorphism at the myotonin protein kinase gene (DMPK) in 102 Japanese families, of which 93 were affected with myotonic dystrophy (DM). All of the affected chromosomes are in complete linkage disequilibrium with theAlu insertion allele. Among the normal chromosomes, alleles of CTG repeats 5 and ⩾ 17 are exclusively associated with the insertion allele. On the other hand, intermediate alleles of 11-6 repeats show a significantly greater association with the deletion allele. A strikingly similar pattern of linkage disequilibrium observed in European populations suggests a common origin of the DM mutation in the Japanese and European populations.
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Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion J-P, Hudson T, Sohn R, Zemelman B, Snell RG, Rundle SA, Crow S, Davies J, Shelbourne P, Buxton J, Jones C, Juvonen V, Johnson K, Harper PS, Shaw DJ, Housman DE (1992) Molecular basis of myotonic dystrophy: expansion of trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell 68:799–808
Buxton J, Shelbourne P, Davies J, Jones C, Van Tongeren T, Aslanidis C, Jong P de, Jansen G, Anvret M, Riley B, Williamson R, Johnson K (1992) Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy. Nature 355:547–548
Dada TO (1973) Dystrophia myotonica in Nigerian family. East Afr Med J 50:213–228
Davies J, Yamagata H, Shelbourne P, Buxton J, Ogihara T, Nokelainen P, Nakagawa M, Williamson R, Johnson K, Miki T (1992) Comparison of the myotonic dystrophy associated CTG repeat in European and Japanese populations. J Med Genet 29:766–769
Fu Y-H, Pizzuti A, Fenwick RG Jr, King J, Rajnarayan S, Dunne PW, Dubel J, Nasser GA, Ashizawa T, Jong P de, Wieringa B, Korneluk R, Perryman MB, Epstein HF, Caskey CT (1992) An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science 255:1256–1258
Goldman A, Ramsay M, Jenkins T (1995) New founder haplotypes at the myotonic dystrophy locus in Southern Africa. Am J Hum Genet 56:1373–1378
Harley HG, Brook JD, Rundle SA, Crow S, Reardon W, Buckler AJ, Harper PS, Housman DE, Shaw DJ (1992) Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature 355:545–546
Harper PS (1989)Myotonic dystrophy. 2nd edn. WB Saunders, London
Harper PS, Harley HG, Reardon W, Shaw DJ (1992) Anticipation in myotonic dystrophy: new light on an old problem. Am J Hum Genet 51:10–16
Imbert G, Kretz C, Johnson K, Mandel J-L (1993) Origin of the expansion mutation in myotonic dystrophy. Nat Genet 4:72–76
Krahe R, Eckhart M, Ogunniyi AO, Osuntokun BO, Siciliano MJ, Ashizawa T (1995) De novo myotonic dystrophy mutation in a Nigerian kindred. Am J Hum Genet 56:1067–1074
Lavedan C, Hofmann-Radvanyi H, Boileau C, Bonaïti-Pellié C, Savoy D, Shelbourne P, Duros C, Rabes J-P, Dehaupas I, Luce S, Johnson K, Junien C (1994) French myotonic dystrophy families show expansion of a CTG repeat in complete linkage disequilibrium with an intragenic 1 kb insertion. J Med Genet 31:33–36
Mahadevan M, Tsilfidis C, Sabourin L, Shutler G, Amemiya C, Jansen G, Neville C, Narang M, Barceló J, O'Hoy K, Leblond S, Earle-Macdonald J, Jong P de, Wieringa B, Komeluk RG (1992) Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science 255:1253–1255
Mahadevan MS, Foitzik MA, Surh LC, Korneluk RG (1993) Characterization and polymerase chain reaction (PCR) detection of anAlu deletion polymorphism in total linkage disequilibrium with myotonic dystrophy. Genomics 15:446–448
Neville CE, Mahadevan MS, Barceló JM, Korneluk RG (1994) High resolution genetic analysis suggests one ancestral predisposing haplotype for the origin of the myotonic dystrophy mutation. Hum Mol Genet 3:45–51
Osame M, Furusho T (1983) Genetic epidemiology of myotonic dystrophy in Kagoshima and Okinawa districts in Japan. Rinsho Shinkeigaku 23:1067–1071
Yamagata H, Miki T, Ogihara T, Nakagawa M, Higuchi I, Osame M, Shelbourne P, Davies J, Johnson K (1992) Expansion of unstable DNA region in Japanese myotonic dystrophy patients. Lancet 339:692
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Yamagata, H., Miki, T., Nakagawa, M. et al. Association of CTG repeats and the 1-kbAlu insertion/deletion polymorphism at the myotonin protein kinase gene in the Japanese population suggests a common Eurasian origin of the myotonic dystrophy mutation. Hum Genet 97, 145–147 (1996). https://doi.org/10.1007/BF02265255
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DOI: https://doi.org/10.1007/BF02265255