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

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.

Fog2 excision in mice leads to premature mammary gland involution and reduced Esr1 gene expression.

The critical role for GATA family proteins in maintaining the normal (non-transformed) cell state is corroborated by the recent findings of mutations or methylation in GATA genes both in primary cancers and tumor lines including breast. Previously, microarray profiling studies determined that the highest expression of both GATA3 and ESR1 (estrogen receptor alpha) is seen in tumors associated with the most favorable survival outcomes, whereas the lowest expression of GATA3 is detected in tumor subtypes showing the worst outcomes. At this time, genes and pathways that are regulated by GATA3 in the mammary gland are not well defined. We have previously established a requirement for FOG (Friend Of GATA) cofactors during mouse development. Here we report that in the murine mammary gland Fog2 gene expression is upregulated upon pregnancy and lactation with prominent expression in the epithelial cells of the gland during post-lactational regression. Mammary-specific deletion of Fog2 identified a role for this gene during gland involution; excision of the Fog2 gene leads to the accelerated involution of the gland despite diminished levels of the remodeling enzymes. Importantly, the levels of several genes linked to the control of cancerous transformation in the breast (Esr1, Prg and Foxa1) are significantly reduced upon Fog2 excision. This implicates FOG2 in the maintenance of epithelial cell differentiation in the mammary gland and in performing a protective role in breast cancer.

[Identification of mutation of the phenylalanine hydroxylase gene using an automated DNA sequencer]. / Identifikatsiia mutatsii fenilalaningidroksilazy s ispol'zovaniem avtomaticheskogo sekvenatora DNK.

Mutations were studied in phenylalanine hydroxylase gene of phenylketonuria patients from Kemerovo oblast and Altaiskii krai (15 and 2 families, respectively). The following mutations were identified in exons of this gene: R408W, R261Q, R243Q, Y414C, Y386C, P281L, Y168H, R68S (lead to amino acid substitutions), R243X (leads to stop codon formation), and three splice site mutations (IVS12nt 1g-->a, IVS2nt-13t-->g, IVS7nt 1g-->a).

[Determination of ureaplasma DNA by the competitive and multiplex PCR]. / Opredelenie kolichestv DNK ureaplazm s pomoshch'iu konkurentnoi i multikompleksnoi PTsR.

Quantities of Ureaplasma spp DNA were determined by the methods of competitive and multiplex polymerase chain reactions (PCR). The results obtained by each of the methods were shown to be compatible. It was established that the number of Ureaplasma spp. cells per one epithelial cell in the female cervical canal varied from 0.05 to 10.

[Mutation in the structure of exon 7 of the phenylalanine hydroxylase in phenylketonuria patients from the Novosibirsk area]. / Mutatsii v strukture ékzona 7 gena fenilalaningidroksilazy u bol'nykh fenilketonuriei Novosibirskoi oblasti.

The spectrum and frequency of mutations of exon 7 of the gene for phenylalanine hydroxylase (PAH) were studied in 34 phenylketonuria (PKU) patients living in Novosibirsk oblast. The five most prevalent mutations constituted 17.64% of defective alleles: R243Q (1.47%), R252W (1.47%), R261Q (5.88%), E280K (1.47%), and P281L (7.35%). A neutral polymorphic locus V245V was found within exon 7.

[New polymorphic sites in the structure of the human phenylalanine hydroxylase gene]. / Novye polimorfnye saity v strukture gena fenilalaningidroksilazy cheloveka.

A previously unknown sequence of the human phenylalanine hydroxylase (PAH) gene intron 7 (GeneBank AN AF204239) has been reported. Screening of the group of phenylketonuria patients from Nobosibirsk region for polymorphic sites within intron 7 revealed single nucleotide substitutions at intron positions 332, 451, 574 and 791. Polymorphic site at intron position 791 corresponds to one of the eight restriction sites (MspI) utilized for haplotype construction. Analysis of the MspI allele frequencies in 29 phenylketonuria patients showed that the frequency of the MspI+ allele in this group was 79.4%. Polymorphic sites at nucleotide position +97 from the beginning of intron 10, and at nucleotide position -54 from the end of intron 5, were also described. The polymorphic sites revealed can be used as markers for identification of the PAH alleles in population genetic studies, and also serve for diagnostics of phenylketonuria (PKU). The presence of numerous nucleotide substitutions within the intronic sequences confirms highly polymorphic structure of the PAH gene.

[Spectrum and methods of detection of mutations in a phenylalanine hydroxylase gene from patients with phenylketonuria from the Novosibirsk region]. / Spektr i metody detektsii mutatsii v gene fenilalaningidroksilazy bol'nykh fenilketonuriei Novosibirskoi oblasti.

Phenylketonuria (PKU) is a widespread autosome recessive hereditary disease caused by a deficiency of the liver enzyme phenylalanine hydroxylase, which results in the distortion of phenylalanine metabolism and accumulation of toxic metabolites. The knowledge of molecular bases of PKU is of a high social importance as it enables phenotypic correction of the disease in the case of its early diagnostics. This disease is known to be associated with mutations in the phenylalanine hydroxylase gene, the distribution and mutation spectrum having pronounced ethnic and regional features. We studied the spectrum of mutations in the phenylalanine hydroxylase gene in a group of patients with PKU from the Novosibirsk region to reveal 10 missense point mutations, 1 mutation in the splice donor site, and 1 microdeletion. For these mutations, most widely distributed in the region, we used straightforward detection methods based on the restriction fragment length polymorphism (RFLP), artificial constructed restriction sites (ACRS) PCR, and denaturing gradient gel electrophoresis (DGGE).

[Nucleotide sequence of rat tyrosine aminotransferase gene]. / Nukleotidnaia posledovatel'nost' gena tirozinaminotransferazy krysy.

The previously unknown sequences of the coding and 3'-flanking regions of the rat tyrosine aminotransferase gene were determined. The boundaries of exons and repetitive elements were established using computer analysis.

[Localization of putative elements of 5'-region of human tyrosine aminotransferase gene mediating its expression by glucocorticoids]. / Lokalizatsiia élementov 5'-oblasti gena tirosinaminotransferazy cheloveka, predpolozhitel'no oposreduiushchikh reguliatsiiu ego èkspresii gliukokortikoidami.

The sequence of the region from -1990 to -580 bp of the human tyrosine aminotransferase gene was determined. Computer analysis revealed putative binding sites for the glucocorticoid-receptor complex which mediates regulation of expression of the gene.