Abstract
The differences in the polymorphic allele frequency distribution patterns of the biallelic (M470V and TUB20) and microsatellite (IVS6aGATT, IVS8CA, and IVS17CA) markers within the CFTR gene between normal and delF508 chromosomes have been established. For most of the marker loci similar distribution of the allele frequencies on normal and mutant chromosomes without delF508 was demonstrated. Certain polymorphic alleles displayed substantial linkage disequilibrium with the delF508 mutation. Analysis of the IVS6aGATT-IVS8CA-M470V-IVS17CA-TUB20 haplotypes association on normal and mutant chromosomes provided identification of the delF508 ancestral haplotype. It was suggested that delF508 mutant chromosomes were introduced into the modern Bashkir gene pool as a result of Slavic migrations from the Eastern Europe. The IVS6aGATT-IVS8CA-M470V-IVS17CA-TUB20major haplotype (77272) revealed was statistically significantly most frequently found on the mutant chromosomes without the delF508 mutation. This finding suggests that the Bashkir cystic fibrosis patients, mostly belonging to the Turkic-speaking families, possessed specific CFTR gene defect associated with the given haplotype.
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References
Kerem, B., Rommens, J.M., Buchanan, J.A., et al., Identification of the Cystic Fibrosis Gene: Genetic Analysis, Science, 1989, vol. 245, pp. 1073–1080.
Riordan, J.M., Rommens, J.M., Kerem, B., et al., Identi-fication of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNA, Science, 1989, vol. 245, pp. 1066–1073.
Rommens, J.M., Iannuzzi, M.C., Kerem, B., et al., Identification of Cystic Fibrosis Gene: Chromosome Walking and Jumping, Science, 1989, vol. 245, pp. 1059–1065.
The CF Mutation Database, 2002, http://www. genet.sickkids.on.cax/cftr.
Korytina, G., Victorova, T., Ivaschenko, T., et al., The Mutation Spectrum of CFTR Gene in the CF Patients from Bashkortostan, Eur. J. Hum. Genet., 2002, no. 10, p. 179.
Nakamura, Y., Leppert, M., O'Connell, P., et al., Variable Number of Tandem Repeat (VNTR) Markers for Human Gene Mapping, Science, 1987, vol. 235, pp. 1616–1622.
Jeffreys, A.J., Royle, N.J., Wilson, V., et al., Spontaneous Mutation Rates to New Length Alleles at Tandem-Repetitive Hypervariable Loci in Human DNA, Nature, 1988, vol. 332, pp. 278–281.
Morral, N., Bertranpetit, J., and Estivill, X., The Origin of the Major Cystic Fibrosis Mutation (delF508) in European Populations, Nat. Genet., 1994, vol. 7, pp. 169–175.
De Vries, II.G., van der Meulen, M., Rozen, R., et al., Haplotype Identity between Individuals Who Share a CFTR Mutation Allele “Identical by Descent”: Demonstration of the Usefulness of Haplotype-Sharing Concept for Gene Mapping in Real Populations, Hum. Genet., 1996, vol. 98, pp. 304–309.
Dork, Th., Neumann, T., Wulbrand, U., et al., Intra-and Extragenic Marker Haplotypes of CFTR Mutations in Cystic Fibrosis Families, Hum. Genet., 1992, vol. 88, pp. 417–425.
Mathew, C.C., The Isolation of High-Molecular-Weight Eukaryotic DNA, Methods in Molecular Biology, Walker, J.M., Ed., New York: Humana, 1984, pp. 31–34.
Ivashchenko, T.E. and Baranov, V.S., Biokhimicheskie i molekulyarno-geneticheskie osnovy patogeneza mukovistsidoza (Biochemical and Molecular Genetic Factors Underlying Cystic Fibrosis), St. Petersburg: Intermedika, 2002.
Schneider, S., Roessli, D., and Excoffier, L., ARLEQUIN Ver 2.0: A Software for Population-Genetics Data Analysis, Genetics and Biometry Laboratory, Geneva: Univ. of Geneva, 2000.
Swofford, L. and Selander, B., BIOSYS-2: Computer Program for the Analysis of Allelic Variation in Genetics, Univ. of Illinois, Current Release, 1997.
Roff, D.F. and Bentzen, P., The Statistical Analysis of Mitochondrial DNA: ϰ2and the Problem of Small Samples, Mol. Biol. Evol., 1989, vol. 6, pp. 539–545.
Zhivotovsky, L.A., Populyatsionnaya biometriya (Population Biometry), Moscow: Nauka, 1991.
Nei, M., Molecular Evolutionary Genetics, New York: Columbia Univ. Press, 1987.
Krawczak, M., Konecki, D.S., Schmidtke, I., et al., Allelic Association of the Cystic Fibrosis Locus and Two DNA Markers, Xv-2c and KM-19 in 55 German Families, Hum. Genet., 1988, vol. 80, pp. 78–80.
Bandelt, H.J., Phylogenetic Network, Verh. Naturwiss. Ver. Hamburg, 1994, vol. 34, pp. 51–71.
Chebab, F.F., Johnson, J., Louie, E., et al., A Dimorphic 4-bp Repeat in the Cystic Fibrosis Gene Is in Absolute Linkage Disequilibrium with the delF508 Mutation: Implications for Prenatal Diagnosis and Mutation Origin, Am. J. Hum. Genet., 1991, vol. 48, pp. 223–226.
Morral, N., Nunes, V., and Casals, T., CA/GT Microsatellite Allele within the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene Are not Generated by Unequal Crossing Over, Genomics, 1991, vol. 10, pp. 692–698.
Morral, N., Dork, Th., et al., Haplotype Analysis of 94 Cystic Fibrosis Mutations with Seven Polymorphic CFTR DNA Markers, Hum. Mutat., 1996, vol. 8, pp. 149–159.
Amosenko, F.A., Sazonova, M.A., Kapranov, N.I., et al., Analysis of Several Polymorphic Markers of the CFTR Gene in Cystic Fibrosis Patients and Healthy Donors from the Moscow Region, Genetika (Moscow), 1995, vol. 31, no. 4, pp. 532–535.
Ivashchenko, T.E., Cystic Fibrosis: Molecular Genetic Analysis of the Gene, Development of New Approaches to Diagnostics and Therapy, Doctoral (Med.) Dissertation, Moscow, 2000.
Sazonova, M.A., Amosenko, F.A., Kapranov, N.I., and Kalinin, V.N., Molecular Genetic Analysis of Intergenic Polymorphisms of the TUB18 and TUB20 Genes and Several Mutations of the CFTR Gene in the Moscow Region, Genetika (Moscow), 1997, vol. 33, no. 9, pp. 1303–1307.
Petrova, N.V., Relative Frequencies of Several Mutations of the CFTR Gene and Analysis of Haplotypes with Linked DNA Markers in Populations of Russia, Cand. Sci. (Biol.) Dissertation, Moscow, 1996.
Claustres, M., Desgeorges, M., Moine, P., et al., CFTR Haplotype Variability for Normal and Mutant Genes in Cystic Fibrosis Families from Southern France, Hum. Genet., 1996, vol. 948, pp. 336–344.
Gimbovskaya, S.D., Kalinin, V.N., Ivashchenko, T.E., and Baranov, V.S., Polymorphic Markers Linked with the Cystic Fibrosis Gene in the Moldova Republic: Characterization of Haplotypes and Their Linkage with Various Mutations, Genetika (Moscow), 1994, vol. 30, no. 12, pp. 1616–1620.
Angelicheva, D., Calafell, F., Savov, A., et al., Cystic Fibrosis Mutations and Associated Haplotypes in Bulgaria—A Comparative Population Genetic Study, Hum. Genet., 1997, vol. 99, pp. 513–520.
Schwarz, M., Anuret, M., Claustres, M., et al., 394delTT: A Nordic CF Mutation, Hum. Genet., 1994, vol. 93, pp. 157–161.
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Korytina, G.F., Victorova, T.V., Ivashchenko, T.E. et al. Analysis of the Polymorphic Markers within the CFTR Gene in Cystic Fibrosis Patients and Healthy Donors from Bashkortostan. Russian Journal of Genetics 39, 1306–1312 (2003). https://doi.org/10.1023/B:RUGE.0000004146.06346.1b
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DOI: https://doi.org/10.1023/B:RUGE.0000004146.06346.1b