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Polymorphism of Trinucleotide Repeats at Loci FRAXA and FRAXE in the Population of Tomsk

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Abstract

Polymorphism of CGG and GCC trinucleotide repeats, whose expansions at the FRAXA and FRAXE loci have been identified as causative mutations in two forms of mental retardation, was studied in Slavic population of Tomsk. At the FRAXA locus a total of 31 allelic variants ranging from 8 to 56 copies of CGG repeat with two modal classes of 28–29 and 18–20 repeat units (with the frequencies of 24.6 and 11.5% respectively) were revealed. Compared to other populations, this locus was characterized by unusually high frequency of intermediate alleles with the sizes of more than 40 CGG repeat units (12.4%). Since intermediate repeats of the FRAXAlocus were more prone to instability than normal alleles, it was suggested that Slavic population of Siberia had higher risk of the development of FMR1 dynamic mutations, giving rise to the Martin–Bell syndrome. The FRAXE allele frequency distribution was demonstrated to be normal with 18 allelic variants ranging from 9 to 27 GCC repeat units. In the population of Tomsk this locus had higher than in other populations frequency (26.7%) of short (less than 15 repeat units in size) alleles. In addition, in the Tomsk population both loci were characterized by high level of heterozygosity and low frequencies of modal allele classes. These results can be explained by the high level of outbreeding typical of the population of Siberia.

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REFERENCES

  1. Richards, R.I. and Sutherland, G.R., Dynamic Mutation: A New Class of Mutation Causing Human Disease, Cell (Cambridge, Mass.), 1992, vol. 70, pp. 709-712.

    Google Scholar 

  2. Morton, N.E. and Macpherson, J.N., Population Genetics of the Fragile-X Syndrome: Multiallelic Model for the FMR1 Locus, Proc. Natl Acad. Sci. USA, 1992, vol. 89, pp. 4215-4217.

    Google Scholar 

  3. Imbert, G., Kretz, C., Johnson, K., et al., Origin of the Expansion Mutation in Myotonic Dystrophy, Nat. Genet., 1993, vol. 4, no. 1, pp. 72-76.

    Google Scholar 

  4. Rubinszshein, D.C., Amos, W., Leggo, J., et al., Mutational Bias Provides a Model for the Evolution of Huntington's Disease and Predicts a General Increase in Disease Prevalence, Nat. Genet., 1994, vol. 5, pp. 525-531.

    Google Scholar 

  5. Murray, A., Youings, S., Dennis, N., et al., Population Screening at the FRAXA and FRAXE Loci: Molecular Analyses of Boys with Learning Difficulties and Their Mothers, Hum. Mol. Genet., 1996, vol. 5, no. 6, pp. 727-735.

    Google Scholar 

  6. Larsen, L.A., Grónskov, K., Norgaard-Pedersen, B., et al., High-Throughput Analysis of Fragile X (CGG)n Alleles in the Normal and Premutation Range by PCR Amplification and Automated Capillary Electrophoresis, Hum. Genet., 1997, vol. 100, pp. 564-568.

    Google Scholar 

  7. Li, C.C., First Course in Population Genetics, Pacific Grove: Boxwood, 1976.

    Google Scholar 

  8. Borovikov, V.P., Populyarnoe vvedenie v programmu STATISTICA (Accessible Introduction to the STATISTICA Program), Moscow: Komp'yuterPress, 1998.

    Google Scholar 

  9. Kunst, C.B., Zerylnick, C., Karickhoff, L., et al., FMR1 in Global Population, Am. Hum. Genet., 1996, vol. 58, pp. 513-522.

    Google Scholar 

  10. Fu, Y.-H., Kuhl, D.P.A., Puzzuti, A., et al., Variation of the CGG Repeat at the Fragile X Site Results in Genetic Instability: Resolution of the Sherman Paradox, Cell (Cambridge, Mass.), 1991, vol. 67, pp. 1047-1058.

    Google Scholar 

  11. Chiang, S.-C., Lee, Y.-M., Wang, T.-R., and Hwu, W.-L., Allele Distribution at the FMR1 Locus in the General Chinese Population, Clin. Genet., 1999, vol. 55, pp. 352-355.

    Google Scholar 

  12. Zong, N., Lui, X., Gou, S., et al., Distribution of FMR1 and Associated Microsatellite Alleles in the Normal Chinese Population, Am. J. Med. Genet., 1994, vol. 51, pp. 417-422.

    Google Scholar 

  13. Crawford, D.C., Schwartz, C.E., Meadows, K.L., et al., Am. J. Hum. Genet., 2000, vol. 66, pp. 480-493.

    Google Scholar 

  14. Morris, A., Morton, N.E., Collins, A., et al., An N-Alleles Model for Progressive Amplification in the FMR1 Locus, Proc. Natl Acad. Sci. USA, 1995, vol. 92, pp. 4833-4837.

    Google Scholar 

  15. Haddad, L.A., Aguiar, M.J.B., Costa, S.S., et al., Fully Mutation and Gray-Zone FRAXA Alleles in Brazilian Mentally Retarded Boys, Am. J. Med. Genet., 1999, vol. 84, pp. 198-201.

    Google Scholar 

  16. Kunst, C.B. and Warren, S.T., Cryptic and Polar Variation of the Fragile Z Could Result in Redispotion Normal Alleles, Cell (Cambridge, Mass.), 1994, vol. 54, pp. 853-861.

    Google Scholar 

  17. Eichler, E.E., Holden, J.A., Popovich, B.W., et al., Length of Uninterrupted CGG Repeats Determines Instability in the FMR1 Gene, Nat. Genet., 1994, no. 8, pp. 88-94.

  18. Zhong, N., Ju, W., Pietrofesa, J., et al., Fragile X “Gray Zone” Alleles: AGG Patterns, Expansion Risk, and Associated Haplotypes, Am. J. Med. Genet., 1996, vol. 64, pp. 261-265.

    Google Scholar 

  19. Knight, S.J.L., Voelckel, M.A., Hirst, M.C., et al., Triplet Repeat Expansion at the FRAXE and X-Linked Mild Mental Handicap, Am. J. Hum. Genet., 1994, vol. 55, pp. 81-86.

    Google Scholar 

  20. Zong, N., Ju, W., Curley, D., et al., A Survey of FRAXE Allele Size in Three Populations, Am. J. Med. Genet., 1996, vol. 65, pp. 415-419.

    Google Scholar 

  21. Ritchie, R.J., Chakraborti, L., Knight, S.J.L., et al., Population Genetics of the FRAXE and FRAXF GCC Repeats, and a Novel CGG Repeat, in Xq28, Am. J. Med. Genet., 1997, vol. 73, pp. 463-469.

    Google Scholar 

  22. Váisánen, M.L., Haataja, R., and Leisti, J., Decrease in the CGGn Trinucleotide Repeat Mutation of the Fragile X Syndrome to Normal Size Range during Parental Transmission, Am. J. Hum. Genet., 1996, vol. 59, pp. 540-546.

    Google Scholar 

  23. Knight, S.J.L., Flannery, A.V., et al., Trinucleotide Repeat Amplification and Hypermethylation of a CpG Island in FRAXE Mental Retardation, Cell (Cambridge, Mass.), 1993, vol. 74, pp. 127-134.

    Google Scholar 

  24. Kucher, A.R., Ivanova, O.F., Puzyrev, V.P., et al., Genetic Demographic Characterization of a Modern Siberian Town (Exemplified by Tomsk), Genetika (Moscow), 1995, vol. 30, no. 2, pp. 276-281.

    Google Scholar 

  25. Amos, W., Sawcer, S.J., Feakes, R.W., et al., Microsatellites Show Mutational Bias and Heterozygote Instability, Nat. Genet., 1996, vol. 13, no. 4, pp. 390-391.

    Google Scholar 

  26. Weber, J.L. and Wong, C., Mutation of Human Short Tandem Repeats, Hum. Mol. Genet., 1993, vol. 2, pp. 1123-1128.

    Google Scholar 

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  1. Institute of Medical Genetics, Tomsk Research Center, Russian Academy of Medical Sciences, Tomsk, 634050, Russia

    E. N. Tolmacheva & S. A. Nazarenko

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  1. E. N. Tolmacheva
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  2. S. A. Nazarenko
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Tolmacheva, E.N., Nazarenko, S.A. Polymorphism of Trinucleotide Repeats at Loci FRAXA and FRAXE in the Population of Tomsk. Russian Journal of Genetics 38, 205–209 (2002). https://doi.org/10.1023/A:1014394329797

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