[Modern approaches to the primary prevention of the development of psychoactive substance dependence on the base of accounting of environmental and genetic risk factors].

In the work there was performed an assessment of the interaction of microsocial and genetic factors of the development of psychoactive substance (PS) dependence. The objects of the psycho-hygienic and molecular-genetic studies were 538 male patients from the specialized diagnostic and treatment center at the age from 17 to 65 years with a diagnosis of "PS dependence" according to F10-F09 in the ICD-10. There were determined personality predictors of early (before 25 years) manifestation of systematic abuse, such as low self-control, individualisticity, authoritarianism, unjustified optimism and reduced capacity for social adaptation. Manifestation of the PS dependence at an early age (25 years) is determined by the contribution of genotype 9R+ DAT gene in the combination with other predisposing genotypes A1 + DRD2/ANKK1, SS SERT and 7R+ DRD. The risk of development of PS dependence at a more younger age increases with the superimposition of individual predisposing genotypes ranging from 1,2 (7R+ gene DRD4) to 1,9 (A1 + gene DRD2/ANKK10 on a destructive milieu. Pairwise combinations of genotypes 7R+ DRD4 x A1+ DRD2, 7R+ DRD4 x 9R+ DAT, 9R+ DAT x A1+ DRD2, 9R+ DAT x SS SERT significantly increase the risk by 2 or more times (2.5-2.8). There was suggested an algorithm for the prenosological forecast of the development of PS dependence in adolescents and young men.

[Phenotypic polymorphism of biomedical parameters of the health status in hygienic studies].

The paper presents the results of investigating the phenotypic polymorphism of a number of biochemical and immunological parameters (the values of oxidative stress, the activity of catalase and glutathione-S-transferase in red blood cells, the serum levels of catecholamines, tumor-necrosis factor-?, and IgG antibody subclasses) in the authors' hygienic studies of genotypic and nongenotypic population samples.

[Association between dopamine (DRD2) and serotonin (5HTR2A) gene polymorphisms with the indicators of adolescent behavior adaptiveness].

The paper gives the results of a study of the impact of dopamine (DRD2) and serotonin (5HTR2A) genes on the development of personality characteristics in adolescents, by applying the Cattell (16PF) questionnaire. The study was performed in a group of 360 Moscow teenagers (185 girls and 175 boys) aged 14-17 years. The boys carrying the A1 allelle of the DRD2 gene were found to have a lower self-control, indiscipline, and impulsiveness. An association between the indicators of unconscientiousness, social introversion, and group independence was established in the girls with the G/G genotype of the 5HTR2A gene. Thus, gender differences have been revealed from the impact of dopamine and serotonin gene polymorphisms on the teenagers' personality characteristics that characterize the forms of disadaptive behavior, such as unconscientiousness, indiscipline, low self-control, and impulsiveness.

[The human son gene: the large and small transcripts contains various 5'-terminal sequences]. / Gen son cheloveka: bol'shoi i malyi transkripty soderzhat raznye 5'-kontsevye posledovatel'nosti.

Human son gene was previously identified by cloning and hybridization to GC-rich rat genomic fragment. After several cycles of human placenta library walking we were able to identify and clone two alternative transcripts of this gene. Recently we have determined nucleotide sequence of small son gene transcript, coding region of which contains four areas of complete tandem repeats. Here we report the structure of the part (2.9 kb) of large transcript of son gene from close to its 5'-end to the end of sequence, unique for this transcript. Comparison of nucleotide sequences of two transcripts indicates that they have common 3'-ends and, probably, arise from alternative splicing. 5' proximal part of large transcript contains two areas of complete tandem repeats not present in small transcript. Results of analysis of this area support our model for forming son gene tandem repeats structure by duplication, mutation and natural selection at the protein level.

[son Pseudogenes do not contain five repeating elements of the region of complete tandem repeats present in the homologous sequence of the son gene]. / Psevdogen son ne soderzhit piati povtoriaiushchikhsia élementov oblasti sovershennykh tandemnykh povtorov, prisutstvuiushchikh v gomologichnoi posledovatel;nosti gena son.

Recently we have published a sequence of the coding region of the son gene, containing at least six areas of the tandem repeats [V.V. Bliskovsky, F.B. Berdichevsky, A.V. Tkachenko, M.E. Belova, I.M. Chumakov--Molecularnaya biologiya, 1992, V. 26. P. 793-806; V.V. Bliskovsky, A.V. Kirillov, V.M. Zacharyev, I.M. Chumakov--Molecularnaya biologiya, 1992, V. 26. P. 807-812]. The presence of several areas of tandem repeats with different nucleotide sequences of the repeated elements within one and the same gene supports the proposition that genomic localization of the sequence influences its duplication. Here we present a nucleotide sequence of the son pseudogene isolated as the result of hybridization screening of a human genomic library using the sequence of the son gene as a probe. The comparison of the gene and the pseudogene nucleotide sequences shows that the sequence of pseudogene does not contain five repeated units of an area of the tandem repeats, which are presented in the homology sequence of the son gene. Because the pseudogene was probably generated by the reverse son-gene transcript insertion to the genome, and so the nucleotide sequences of the coding region of the gene and the sequence of the pseudogene were identical at this moment, the differences between the gene and the pseudogene are the results of their evolution after the generation of the pseudogene. Possible factors, influenced the son gene and the son pseudogene evolution are discussed.

[Stable maintenance of dicentric mini-chromosomes in CHL4 mutants in yeast]. / Stabil'noe podderzhanie ditsentricheskikh mini-khromosom u mutanta drozhzhei po genu chl4.

Earlier we have identified the chl4-1 mutation in a screen for yeast mutants with increased loss of chromosome III and circular artificial minichromosome in mitosis. Mutation in the CHL4 gene leads to a 50-100-fold promotion in the rate of chromosome loss per cell division compared to the isogenic wild type strain. Detailed analysis of behaviour of the circular minichromosome marked by the CUP1 gene has shown that minichromosome nondisjunction (2:0 segregation) leading to an increase in the copy number of minichromosome in part of a cell population is the main reason of minichromosome instability in the mutant. The unique peculiarity of chl4-1 mutation is the ability of the strains carrying this mutation to stably maintain circular dicentric minichromosomes without any rearrangement during many generations. (In the wild type strains dicentric minichromosomes are extremely unstable. As a consequence of that there is a strong selection for cells harboring monocentric derivatives in a population of cells derived from a cell containing a dicentric plasmid). Introduction of the second centromere into one of the natural chromosomes (chromosomes II or III) in the chl4-1 mutant leads to the same dramatic consequences as that in the wild type strain (mitotic lag of cells harboring dicentric chromosomes and, as a result of that, selective pressure for cells harboring monocentric derivatives of dicentric chromosome). A genomic clone of CHL4 was isolated by complementation of the chl4-1 mutation. Nucleotide sequence analysis of CHL4 revealed a 1.4-kb open reading frame with a predicted 53-kDa protein sequence. Analyzing the sequence of the CHL4 protein we have found a region meeting the necessary requirements for the helix-turn-helix (HTH) structure. This region of the CHL4 protein has about 40% homology with the repressor of tryptophane operon (TrpR) of E. coli. A strain containing a null allele of CHL4 was viable under standard growth conditions, but had temperature-sensitive phenotype (conditional lethality at 34 degrees C). We suggest that the CHL4 gene product is one of the components of the segregation cell machinery.

[CHL15--a new gene controlling the replication of chromosomes in saccharomycetes yeast: cloning, physical mapping, sequencing, and sequence analysis]. / CHL15--novyi gen, kontroliruiushchii replikatsiiu khromosom u drozhzhei--sakharomitsetov: klonirovanie, fizicheskoe kartirovanie, sekvenirovanie i funktsional'nyi analiz.

We have analyzed the CHL15 gene, earlier identified in a screen for yeast mutants with increased loss of chromosome III and artificial circular and linear chromosomes in mitosis. Mutations in the CHL15 gene lead to a 100-fold increase in the rate of chromosome III loss per cell division and a 200-fold increase in the rate of marker homozygosis on this chromosome by mitotic recombination. Analysis of segregation of artificial circular minichromosome and artificially generated nonessential marker chromosome fragment indicated that sister chromatid loss (1:0 segregation) is a main reason of chromosome destabilization in the chl15-1 mutant. A genomic clone of CHL15 was isolated and used to map its physical position on chromosome XVI. Nucleotide sequence analysis of CHL15 revealed a 2.8-kb open reading frame with a 105-kD predicted protein sequence. At the N-terminal region of the protein sequences potentially able to form DNA-binding domains defined as zinc-fingers were found. The C-terminal region of the predicted protein displayed a similarity to sequence of regulatory proteins known as the helix-loop-helix (HLH) proteins. Data on partial deletion analysis suggest that the HLH domain is essential for the function of the CHL15 gene product. Analysis of the upstream untranslated region of CHL15 revealed the presence of the hexamer element, ACGCGT (an MluI restriction site) controlling both the periodic expression and coordinate regulation of the DNA synthesis genes in budding yeast. Deletion in the RAD52 gene, the product of which is involved in double-strand break/recombination repair and replication, leads to a considerable decrease in the growth rate of the chl15 mutant. We suggest that CHL15 is a new DNA synthesis gene in the yeast Saccharomyces cerevisiae.

[Characteristics of the pH2-42 probe for the D13S25 locus of human chromosome 13: nucleotide sequence, localization, and PCR markers]. / Kharakteristika proby pH2-42 lokusa D13S25 13-i khromosomy cheloveka: nukleotidnaia posledovatel'nost', lokalizatsiia, PTsR-markery.

The sequence of the HindIII-HindIII fragment of probe pH2-42 of locus D13S25 of human genome is given. Localization of the probe in q14-q21 of human chromosome 13 is confirmed by hybridization in situ. Seven oligonucleotide primers for the polymerase chain reaction are chosen so that amplified products almost completely cover the analyzed sequence. Reconstruction of localization of polymorphic SspI-sites in D13S25 was based on the data of Bowcock and Hebert [3] and this study. The results obtained make it possible to use the primer sets to screen cosmid libraries and to mark the D13S25 locus of human chromosome 13.

[Cloning and nucleotide sequence determination of the aadB gene from a Salmonella oranienburg strain]. / Klonirovanie i opredelenie nukleotidnoi posledovatel'nosti gena aadB iz shtamma Salmonella oranienburg.

Cloning and nucleotide sequence determination of the aadB gene and boundary DNA fragments from a high molecular weight plasmid of Salmonella oranienburg were performed. The data on the restriction mapping showed that the aadB gene was located within the integrone. Analysis of the nucleotide sequence of the cloned fragment revealed a high level conservative nature of the aadB gene and boundary DNA areas.