Independent origin of rare Y168H mutation of human phenylalanine hydroxylase gene in Russia

E. V. Brenner1, F. O. Smagulova1, I. V. Morozov1
1Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Novosibirsk, Russia

Tóm tắt

mutation Y168H of the human phenylalanine hydroxylase (PAH) gene determining phenylketonuria was described only twice: in a patient from Catalonia (Spain) and by us in a patient from Western Siberia (Russia). The association of Y168H in these families with allelic variants of STR and VNTR repeats and a number of neutral point polymorphisms of the PHA gene (IVS3nt-22C > T, Q232Q, V245V, L385L) was studied in this work. The Y186H mutation in these families was found to be associated with different haplotypes. Strong linkage of the selected markers and the mutation region excludes recombination as a possible cause of association of Y168H with different haplotypes. It was concluded that Y168H occurred independently in different populations.

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Tài liệu tham khảo

Zschocke, J., Phenylketonuria Mutations in Europe, Hum. Mutat., 2003, vol. 21, no. 4, pp. 345–356. Byck, S., Morgan, K., Tyfield, L., et al., Evidence for Origin, by Recurrent Mutation, of the Phenylalanine Hydroxylase R408W Mutation on Two Haplotypes in European and Quebec Populations, Hum. Mol. Genet., 1994, vol. 3, no. 9, pp. 1675–1677. Zschocke, J. and Hoffmann, G., Phenylketonuria Mutations in Germany, Hum. Genet., 1999, vol. 104, no. 5, pp. 390–398. Mallolas, J., Vilaseca, M.A., Campistol, J., et al., Clinical, Biomedical, Neurological and Molecular Study of 11 Patients with New Mutations in PAH Gene, Rev. Neurol., 2000, vol. 31, no. 10, pp. 907–910. Smagulova, F.O., Brenner, E.V., Kotova, L.Yu., et al., Identification of Mutation of the Phenylalanine Hydroxylase Gene Using an Automated Genetic Analyzer, Russ. J. Genet., 2004, vol. 40, no. 2, pp. 208–211. Daiger, S.P., Lidsky, A.S., Chakraborty, R., et al., Effective Use of Polymorpic DNA Haplotypes at the Phenylalanine Hydroxylase (PAH) Locus in Prenatal Diagnosis of Phenylketonuria, Lancet, 1986, vol. 1, pp. 229–232. Scriver, C.R., Beaudet, A., Sly, W.S., et al., The Metabolic and Molecular Bases of Inherited Disease, New York: McGraw-Hill, 2001. De La Vega F.M., Isaac, H.I., and Scafe, C.R., A Tool for Selecting SNPs for Association Studies Based on Observed Linkage Disequilibrium Patterns, in Pacific Symposium on Biocomputing 11, 2006, pp. 487–498. Maniatis, N., Collins, A., Xu, C.F., et al., The First Linkage Disequilibrium (LD) Maps: Delineation of Hot and Cold Blocks by Diplotype Analysis, Proc. Natl. Acad. Sci. USA, 2002, vol. 99, no. 4, pp. 2228–2233. Byck, S., Tyfield, L., Carter, K., and Scriver, C.R., Prediction of Multiple Hypermutable Codons in the Human PAH Gene: Codon 280 Contains Recurrent Mutations in Quebec and Other Populations, Hum. Mutat., 1997, vol. 9, pp. 316–321.