To date, about 7,000 hereditary diseases are known. However, modern diagnostic methods reveal the cause of the disease in about 40% of cases. This is partly due to the complexity and wide variety of molecular mechanisms of pathogenesis. MicroRNAs are one of the most powerful genes expression regulators. But their participation in the pathogenesis of hereditary diseases has not yet been studied enough because of the difficulties in finding such disorders. In this work, we collected and analyzed pathogenesis of hereditary diseases mediated by dysregulation of gene expression by microRNA. such cases have been identified for such hereditary diseases as cystic fibrosis, Duchenne muscular dystrophy, beta-thalassemia, glaucoma, facioscapulohumeral muscular dystrophy Landouzy-Dejerine, Hirschsprung disease, Rett syndrome, Tourette syndrome, pemphigus (Hailey-Hailey disease).

Identification of genomic imbalances in cases with balanced chromosomal rearrangements and abnormal phenotype is a current trends in cytogenetics practice, requiring the development of unique approach using modern molecular genetic technologies. The aim of this study is diagnostics etiologies of the abnormal phenotype in patients with balanced chromosomal rearrangements. We report the investigations results of 20 patients with abnormal phenotype and balanced chromosomal rearrangements by conventional cytogenetic analysis. Genomic imbalances by microarray studies detected in 13 of 20 cases (65%). Most of CNVs was microdeletion or microduplication at a rearrangement breakpoint (69.2%) and 20.8% microdeletion/microduplication in other chromosomes.

The variety of causes of the articular syndrome (AS) and the similarity of its clinical manifestation in many diseases significantly complicate the differential diagnosis. Despite the prognosis of the juvenile idiopathic arthritis (JIA) depends on the early diagnosis, there are still no highly specific laboratory tests. Objective: to assess the association of the polymorphic loci of the genes involved into the regulation and implementation of the immune system functions with predisposition to the JIA and other joint pathology in children in the Republic of Belarus. Three groups of children: 275 patients with JIA, 230 patients with joint pathology of various origins, with the exception of JIA and 291 children without autoimmune and chronic inflammatory diseases (control) were genotyped for 11 polymorphic loci of 8 genes: STAT4 (rs7574865), CTLA4 (rs231775), PTPN2 (rs2542151, rs7234029), IL-6 (rs1800795), IL-6R (rs2228145, rs4845618), RUNX1 (rs9979383)) TRAF1/C5 (rs3761847) using real-time PCR and PCR-RFLP. It was found that CC genotype at the rs1800795 locus of the IL-6 gene is associated with the JIA in the general (OR 1.75 [1.18 - 2.58], p = 0.0058), and GG genotype at the rs3761847 locus of the TRAF1/C5 gene - with the systemic JIA (OR 2.79 [1.29 - 6.06], p = 0.01). GG genotype at the rs3761847 locus of the TRAF1/C5 (р = 0.04; OR 1.66 [1.03 - 2.68]) gene and CC genotype (р = 0.0002; OR 2.26 [1.47 - 3.47]) as well as C allele (р = 0.006; OR 2,01 [1.14 - 3.52]) at the rs1800795 locus of the IL-6 gene are associated with early-onset JIA (≤ 5 years). The most common JIA subtypes (oligoarthritis, seronegative polyarthritis, systemic arthritis) differ in the prevalence of allelic variants at the rs3761847 loci of the TRAF1/C5 gene and rs7574865 of the STAT4 gene. JIA patients differ significantly from the AS patients at the following loci: IL-6R (rs2228145, rs4845618), FOXP3 (rs2232365), TRAF1/C5 (rs3761847), as well by the frequencies of 33 paired genotype combinations of the studied polymorphisms. Among JIA patients, sex-dependent features of the genotype distribution in polymorphic variants of the IL-6R (rs2228145, rs4845618) and RUNX1 (rs9979383) genes were revealed. Conclusion. The data obtained indicate genetically determined differences between JIA subtypes as between JIA and AS in case of other joint pathology. This can be used as a basis for the additional criteria development for the differential diagnosis of joint diseases in children.

Common and often comorbid cardio- and cerebrovascular diseases (CCVD), including arterial hypertension (AH), coronary heart disease (CHD), and cerebral stroke (CS), are the leading cause of death worldwide. Oxidative stress has many pathological effects on vascular homeostasis and is currently regarded as one of the common mechanisms for the development of CCVD. The aim of our study was to investigate the association of single nucleotide polymorphisms of the redox-homeostasis genes rs2070424 SOD1, rs4880 SOD2, rs769214 CAT, rs713041 GPX4, rs41303970 GCLM, rs17883901 GCLC, rs854560 PON1, rs7493 PON2, rs1695 GSTP1, rs2266782 FMO3 with the development of isolated and comorbid CCVD. A total 2702 individuals of Slavic origin were included for this study. The patients group included 1815 subjects with various CCVD and their combinations: isolated AH (IAH); isolated IHD (IIHD), combination of AH and IHD (AH+IHD); combination of AH and CS (AH+CS); comorbid cardio- and cerebrovascular pathology (AH+IHD+CS). From the total sample of healthy individuals (N=887), 5 sex- and age-matched control groups were formed. Genotyping was performed using TaqMan-based PCR. To analyze the associations of genotypes with the risk of diseases, a log-additive regression model was used. All calculations were performed relative to the minor allele; corrections for gender and age have been introduced. SNP rs1695 GSTP1 was associated with IAH exclusively (OR=1.19, 95%CI=1.01-1.39, P=0.034). SNP rs7493 PON2 was associated with the development of all studied comorbid CCVD: AH+IHD (adjOR=1.32, adj95%CI=1.07-1.63, adjP=0.01); AH+CS (adjOR=1.79, adj95%CI=1.45-2.21, adjP<0.0001); AH+IHD+CS (adjOR=1.51, adj95%CI=1.09-2.09, adjP=0.01), as well as shortening of prothrombin time (adjDifference=-0.35; adjP=0.01). SNP rs2266782 FMO3 was associated with the development of AH+CS (adjOR=1.24, adj95%CI=1.02-1.51, adjP=0.03), as well as decreased age of manifestation of CS (adjDifference=-2.31; adjP=0.03). Thus, it was found that genes involved in regulation of redox-homeostasis, can represent an important genetic component in the formation of differentiation of cardio- and cerebrovascular phenotypes.

According to one of the modern concepts of human aging and longevity, the cause of the degradation of endogenous processes is the increased genome instability with age. Factors of genetic instability include transposons, or mobile genetic elements. Alu-retrotransposons are ubiquitous in the human genome. Among the members of this family, AluYa5 and AluYb8 are the only ones that retained transpositional activity. To test the hypothesis about the role of of AluYa5 and AluYb8 transposons activity in human aging and longevity, we performed the comparative analysis of their expression level among individuals of different ages. The study group included 75 healthy residents of the Republic of Bashkortostan aged between 21 and 97 years. The total sample was divided into the following groups according to age: middle-aged (38 people, 21-39 years old), elderly (23 people, 82-89 years old) and a group of long-livers (14 people, 90-97 years old). RNA samples were isolated from leukocytes of peripheral venous blood by the standard method using Trizol reagent. Quantitative analysis of AluYa5-RNA and AluYb8-RNA in blood leukocytes was performed by real-time PCR. The relative amount of mRNA was determined using the ΔΔCt method. Comparison of age groups was carried out using one-way analysis of variance with the Kruskal-Wallis test. In the total analyzed sample, the expression levels of AluYa5 and AluYb8 were 0.84 and 0.80 rel. units respectively. According to the results of comparative analysis of AluYa5-RNA and AluYb8-RNA in blood leukocytes of people from three age groups, there were no statistically significant differences in the expression of AluYa5 (H = 3.59, p = 0.17) and AluYb8 (H = 2.65, p = 0.27). After combining the groups of elderly people and long-livers and comparing them with middle-aged people, the differences in the median values also did not reach the level of statistical significance (p = 0.1). At the same time, people aged 82 and older demonstrated lower level of expression of AluYa5 subfamily (0.75 versus 2.69 rel. units) and AluYb8 subfamily (0.73 versus 2.15 rel. units). There were no statistically significant changes in the relative expression level of the AluYa5 and AluYb8 subfamilies with age in the study group.

The influence of population-genetic structure on the prevalence of monogenic and multifactorial pathology is no longer in doubt. The purpose of this study is to study the gender and age structure of the population of North Ossetia-Alania in the framework of a comprehensive genetic and epidemiological survey of the population and comparison with the obtained data of distribution of gender and age characteristics of patients with hereditary pathology. On the basis of statistical data as of January 1, 2018, the gender and age structure of North Ossetia population is analyzed by a standard method, 1054 patients with confirmed diagnosis and type of inheritance were identified in 4 districts: Ardonsky, Alagirsky, Pravoberezhny, Kirovsky. Gender and age pyramids for the urban and rural population of North Ossetia, having the form of a bell, between which no significant differences were revealed, were compiled. There has been a slight increase in fertility in the urban population, due to the outflow of young people to the cities from rural areas. The reproductive part does not exceed a quarter of the population. There is a predominance of women in older age groups. The ratio of males to females is 1:1.19 in the urban population, 1:1.11 in the rural population, the ratio is different in different age cohorts. Aging rate 17.2%. The demographic burden ratio is 39.4%. The proportion of children and older persons is almost the same. It is shown that the gender-age structure of North Ossetia is characterized by a stationary type and an old population with a practically simple reproduction character. Among patients with hereditary pathology, other characteristics of the gender and age structure are observed. in all age cohorts, the number of men exceeds the number of women.

The current state of research in the field of genetic toxicology of pharmaceuticals is discussed. Applied and fundamental problems of genetic toxicology are highlighted.

It has been shown that paraquat (1,1-dimethyl-4,4 dipyridylium dichloride) induces luminescence of biosensors carrying the promoters of the soxS and katG genes that specifically react to the superoxide anion radical and hydrogen peroxide. The antioxidants glutathione and acetylcysteine reduced the level of biosensor luminescence and DNA breaks.

A single and repeated doses of nanoparticles caused DNA damage in the liver, lung and kidney of mice as well as in the in vitro comet assay on bone marrow cells. No statistically significant increase in the percentage of cells with chromosomal aberrations was observed in mice treated with nanoparticles after a single or repeated injection.

The genotoxicity of more than 200 technical grade active ingredients (TGAI) of pesticides has been studied. An algorithm for evaluating the equivalence of TGAIs to the original active ingredients upon the criterion of “mutagenicity” has been developed. The necessity of studying the genotoxic activity of the combinations of pesticide active ingredients was substantiated. Limitations of the genotoxicity tests due to toxicity of pesticides of different chemical classes have been established. The dependence of the erythropoiesis-inhibiting action of triazole pesticides on the structure of the active ingredient was revealed. The effects and the general mechanism of the carbendazim action on the processes of karyokinesis, extrusion of nuclei and cytokinesis in mammalian bone marrow erythroid cells were studied. The criteria for expert evaluation of pesticide mutagenicity have been developed.

The induction of cisplatin mutations was studied in female Drosophila carrying yellow, white, singed marker mutations on the same chromosome when crossed with wild-type males Canton-S.

The genotoxicity of some organophosphate pesticides applied in agriculture was studied using the Ames test and the mammalian erythrocyte micronucleus test in vivo. Technical grade active ingredients (TGAI) of chlorpyrifos and diazinon did not show genotoxicity either in vitro or in vivo. The weak mutagenic effects of dimethoate were revealed with bacterial strains. Some TGAIs of glyphosate, dimethoate, and pyrimifos-methyl induced cytogenetic abnormalities in CD-1 mice. The observed effects in vivo were low even at the maximum tolerated doses. Therefore, according to the pesticide hygienic classification adopted in the Russian Federation all studied organophosphate pesticides can be assigned a 3 or 4 class of hazard upon the criterion “mutagenicity”.

The genotoxic effect of paclitaxel on the chromosomal material of differentiated bone marrow cells in male and female mice was revealed in the early and long-term periods of the study. It was found that during the same observation period paclitaxel causes bone marrow hypoplasia and reduces the number of early erythropoiesis progenitor cells in the bone marrow of experimental animals, and also contributes to a decrease in their proliferative potential regardless of gender.

A methodology for evaluating DNA damage in one - and two-cell mouse embryos using the comet assay has been developed. The applicability of the developed methodology for assessing genotoxicity in vivo and in vitro was confirmed in experiments with model genotoxicants - methyl methanesulfonate, dioxidine, etoposide and mitomycin C.

We studied the genotoxic effect of bactericidal agents: dioxine, furaciline and nalidixic acid on cells of the deuterated culture lux-biosensor E. coli MG1655 (pColD::lux), which luminesces as a result of activation of the colicin gene promoter colD in response to DNA damage. For the first time, it was shown that deuterium oxide (D2O) at a concentration of 9% increases the SOS response by 1.6-2.8 times in E. coli cells induced by the studied drugs.

The antimutagenic activity of anti-radiation drugs betaleukin, flagellin, indraline and riboxin with different mechanisms of action was studied in short-term and chronic experiments in mice in vivo. All drugs showed antimutagenic properties in bone marrow cells, as well as hepatoprotective effect. The greatest effect under the used experimental conditions was noted for betaleukin and the new anti-radiation drug flagellin.

Using different concentrations of Achillea millefolium L. extract selected 5% demonstrating more pronounced protective properties regarding the toxic effects of etoposide. They have established stimulation of fertility in the cultivation of individuals on a nutrient medium with extract. Genotoxic manifestations in A. millefolium L. in 5% concentration were not found.

In this study, we investigated the cell survival, the DNA repair foci level and the radiation-induced micronuclei frequency in the model systems in vitro and in the human peripheral blood lymphocytes with differential expression of ADAMTS1, RBFOX2, THBS1 and WHSC1 genes. The results indicate the potential opportunity of using these genes expression level to identify the individuals with increased radiosensitivity.

The effect of mexidol, dihydroquercetin, dibornol and paratyrosol on the amount of DNA damage and the redox potential in rat testicular tissue cells was studied. It was established, that all studied compounds, except mexidol, reduced the number of DNA breaks in the cells and had a normalizing effect on their redox potential under the conditions of DNA damage to spermatogenic tissue cells. The highest therapeutic activity was detected in dihydroquercetin.

Fibroblasts with the mutation of m.14441 T>C in the ND6 gene and fibroblasts of a healthy donor were chosen as a research model. It was shown that this mutation in the ND6 mitochondrial DNA gene has a significant effect on the cellular response during oxidative stress.

The results of the assessment of DNA damage using an alkaline modification of the comet method in samples of fresh and cryopreserved cells at -80 ° C and -196 ° C are presented.

The significance of genomic instability and mutagenesis processes in the mechanisms of cancer formation and the presence of transgenerational phenomenon in I-II generations exposed to the radiation factor was investigated.

The impact of qualitative and quantitative changes in the composition of the bacterial microbiome in the sputum of 17 patients with lung cancer and 17 control donors on the parameters of somatic cell cytogenetic homeostasis was first assessed. Donors with high frequencies of chromosomal aberrations (CA) over 3.5 % had a significant decrease in the microbiome of the genera Prevotella, Selenomonas, Veillonella, as well as an increase in representatives of the genus Kocuria compared to donors with a low level of CA in lymphocytes. At the species level, differences were found in the contents of Anaerosinus glycerini, Selenomonas bovis, Actinomyces hyovaginalis, Granulicatella balaenopterae and Clostridium bolteae. Moreover, only the latter species was represented more often in the sputum of donors with high levels of CA, the remaining 4 types of bacteria were significantly more likely to be present in the sputum of donors with a low level of mutations in lymphocytes.

We studied possible relations between heavy metal content and cytogenetic characteristics of exfoliated buccal cells. To this end, we examined children living in the area where the tungsten-molybdenum plant is located. Despite the increased content of heavy metals in environmental objects, their accumulation in the hair of children was not detected. Significant correlations were found between the content of manganese, zinc and copper in the hair with the indicators of cell proliferation.

There was no reveled induction of genotoxic effects in rat bone marrow at the constant use of “melaxen” at a dose of 10 mg/kg. The chronic joint intragastric injection of a cadmium salt of 0.3 mg / kg (in terms of metal) and “melaxen “ showed the protective properties of the remedy (p<0.01) after metaphase analysis.

Using the micronucleus test, the protective effect of melaxen (10 mg / kg) was shown in chronic experimental cadmium intoxication (0.3 mg / kg) in rat blood, p <0.001. The studied remedy demonstrated the ability to reduce the expected number of micronuclei and polychromatophilic red blood cells (PCE) induced by cadmium during two-week and one-month exposure. In chronic intragastric injection of melaxen, an increase in the number of micronuclei and PCEs was not registered in comparison with the control, p> 0.05.