Mitochondrial forms of hearing loss account for no more than 1-2% among all non-syndromic cases of hearing loss. However, one of the most common causative variants of the mitochondrial genome is m.1555A>G of the MT-RNR1 gene, which is associated with a deafness induced by aminoglycoside antibiotics (OMIM:561000). Currently, the contribution of the mitochondrial deafness to the etiology of hearing loss remains insufficiently studied, since the detection of the m.1555A>G of the MT-RNR1 gene is not included in all research protocols. In this work, using PCR-RFLP analysis followed by Sanger sequencing, the pathogenic variant m.1555A>G of the MT-RNR1 gene for the first time was searched in 165 hearing impaired patients in the Republic of Buryatia. As a result, the m.1555A>G of the MT-RNR1 gene in the homoplasmic state was detected in 21 out of 165 studied patients. The total contribution of the m.1555A>G (MT-RNR1 gene) to the etiology of hearing impairment in Buryatia was 12.7%. At the same time, a high proportion of m.1555A>G of the MT-RNR1 gene was detected in Buryat patients (20.2%), compared to Russian patients (1.3%). A genetic-epidemiological analysis of the identified mitochondrial form of hearing loss revealed its increased prevalence in three south districts in the Republic of Buryatia, with the maximum accumulation in the Dzhidinskii district (4.5 per 10,000 peoples). The analysis of the global prevalence of the variant m.1555A>G of the MT-RNR1 gene among 43435 patients with hearing impairment showed that its share is on average 1.9%. The results obtained on the high contribution of the m.1555A>G to the etiology of hearing impairment in Buryat patients indicate that we have found in the Baikal Lake region one of the largest of the world accumulation of the mitochondrial forms of hearing loss with most likely due to founder effect.

Juvenile idiopathic arthritis (JIA) is ineffective in childhood and adolescence and responds to therapy largely due to genetic differences. The aim of the work was to search for associations of methotrexate therapy in JIA patients with the presence of polymorphic allelic variants of the immune response mediator genes TNF-α rs1800629, IL10 rs1800872 and IL6 rs1800795. The article presents an analysis of the distribution of IL10/IL6 diplotypes and TNF-α/IL10/IL6 triplotypes. The experiments involved 239 patients who received basic therapy with the use of methotrexate. For the purpose of genotyping, the real-time PCR method was used. In the subgroup of RF patients with anegative form of JIA, an association of the polymorphic variant IL10 -592C>A with no effect on methotrexate therapy was found. Ithasbeen established that the presence of one IL10 *A allele increases the likelihood of a lack of response to therapy, while the presence of the *CC genotype increases the chances of a response. A diplotype (IL10*АA/IL6*GC) and a triplotype (TNF-α*GG/IL10*AA/IL6*GC) were identified, which are significantly more common in the general group of patients diagnosed with JIA among patients with no response to methotrexate. It is assumed that the results obtained in further studies can be used as pharmacogenetic predictors of the effectiveness of therapy in patients with JIA.

Sanger sequencing, next generation sequencing, and methyl-sensitive PCR were compared to determine the methylated state of the target locus. The clinical significance of the resulting discrepancies in application to determining the methylation status of the promoter region of the MGMT gene in glioblastoma is discussed. It has been shown that MP-PCR is characterized by false-negative results, and it is also difficult to assess low levels of methylation that do not have clinical significance. Sanger sequencing does not allow profiling individual cell clones and requires separate software to quantify methylation. For routine laboratory practice, a technology of targeted clonal bisulfite DNA sequencing was proposed using a new generation sequencing method to determine the methylation status of a CpG island that includes the MGMT gene promoter region. The use of the Ion Torrent PGM is recommended to avoid calculating correction factors for methylation bias.

Background. The demographic structure of Russian populations has undergone significant changes since 1990, accompanied by unfavorable trends in the processes of population reproduction. Therefore, studies of the dynamics of the formation of urban populations and the analysis of the biological component of the reproduction process, in which reproduction acts as a universal indicator of the social and biological state of society, are relevant.

Aim: to study the temporal variability of selection parameters due to differential fecundity in the Cheboksary population.

Methods. The parameters of differential fertility as components of natural selection (Crow’s index) were calculated according to the obstetric history of post-reproductive age female residents of Cheboksary in 1989, 2019.

Results. In 1989, the narrowed type of population reproduction was observed. There was an average of 5.72±0.29 pregnancies, 1.88±0.07 births, 3.42±0.29 medical abortions, 0.44±0.08 spontaneous abortions, miscarriages, and ectopic pregnancies per woman. Only 32.6% of all pregnancies resulted in a live birth. The decline in the average number of offspring is an indication of the prevalence of birth control practices (abortion, contraception). In 2019, the average number of pregnancies decreased 4.31±0.21, the number of births increased 2.61±0.05, the number of medical abortions decreased sharply 1.39±0.21, and the use of contraceptives increased. The families of Cheboksary have undergone significant changes in their attitudes and strategies towards reproduction. The level of simple reproduction is exceeded in the population (average number of offspring   Ê=2.46±0.08). Increased inter-familial differences in the number of offspring reflect the growth of multi-child families. Higher values are expected to be found in cohorts of individuals who have not finished reproduction.

Conclusion. Positive changes in the reproductive behavior of women in Cheboksary testify to the transition from the strictly regulated nature of narrowed-type reproduction to expanded reproduction.

Atherosclerosis is the leading cause of death worldwide. Despite significant advances in the diagnosis, treatment, and risk stratification of atherosclerosis, there is still a need for new diagnostic biomarkers and therapeutic targets to prevent an epidemic of the disease. Recently, more and more evidence has been published linking dysregulation of microRNAs with cardiovascular disease, including atherosclerosis. MicroRNAs are endogenous, stable, single-stranded, short, non-coding RNAs and can be used as diagnostic and prognostic biomarkers of atherosclerosis.

The aim of our study was to search for an association between polymorphic variants of microRNA genes MIR96 (rs13231740), MIR758 (rs1885068), MIR33a (rs9620000), and the risk of atherosclerosis in residents of the Rostov region.

Venous blood samples from 100 patients (57% of men and 43% of women) with atherosclerosis were collected as material for the study. The control group consisted of 103 people (42,71% of men and 57,29% of women) without cardiovascular diseases. Isolation of genomic DNA from peripheral blood was performed using a QIAamp DNA Blood mini kit (Qiagen, Germany). Genotyping was performed using an allele-specific PCR mixture qPCRmix-HS (Evrogen, Russia) on a Real-time CFX96 Touch device (USA). Analysis of the Hardy-Weinberg equilibrium and differences in the distribution of allele variants between groups of patients and controls were assessed using the χ2test.

To assess the risk of developing atherosclerosis, we used odds ratios (ORs) and confidence intervals (CIs).

The study found that the AC genotype of the MIR96 gene (rs13231740) (OR 1.92 95% CI 1.07–3.45, P=0.02) and the TC and CC genotypes of the MIR33a gene (rs9620000) (OR 4. 85 95% CI 2.35-10.00; OR 4.12 95% CI 1.11-15.24 P=4.0E-7) are associated with an increased risk of atherosclerosis. The presence of the polymorphic allele of the MIR758 gene (rs1885068) is not associated with the development of atherosclerosis. Thus, the results of the study emphasize the importance of searching for diagnostic biomarkers in the noncoding region of the genome.

Structural and numerical rearrangements of the sex chromosomes represent the most commonly observed chromosomal abnormalities that are compatible with live birth. Compared to numerical or structural autosomal rearrangements abnormalities of sex chromosomes tend to have less pronounced clinical consequences. In women with phenotypic manifestations of Turner syndrome, structural anomalies of the X chromosome, particularly in the mosaic form, are frequently observed in the karyotype. However, in individuals with a structurally rearranged sex chromosome, developmental anomalies may be absent. This can be attributed to the absence of cell clone 45,X and selective inactivation of the rearranged X chromosome. The wide phenotypic variability and limited data available on patients with structural anomalies of the X chromosome significantly complicate the process of medical genetic counseling for such patients. In this report, we present a unique case of a pseudotricentric X chromosome featuring a short arm duplication, four copies of the Xq11.1q22 region, and a deletion of the Xq22 long arm terminal region. The aim of the study was to establish the structure and mechanism of the formation of an abnormal X chromosome in a patient with delayed psychomotor and sexual development. A standard cytogenetic study, FISH, chromosomal microarray analysis was carried out. The pseudotricentric X chromosome with a duplicated short arm, partial tetraplication, and a long arm deletion is a unique structural gonosomal rearrangement. An integrated molecular cytogenetic approach made it possible to determine the structure of the derivative X chromosome and establish the genotype-phenotype interaction in the presence of a pseudotricentric X chromosome in the genome.

The number of cases with the description of primary multiple tumors is growing, however, reports of synchronous-metachronous neoplasms are extremely rare. Moreover, there is practically no genetic analysis of such tumors and possible ways of their progression in the literature. The purpose of this study was to establish the independence of the origin of multiple tumors in a patient with Lynch syndrome. A retrospective analysis of the material included both the study of the morphological features of tumors and the detection of mutational damage in the studied genes by whole exome sequencing of DNA isolated from available paraffin blocks. The combination of histological types and established mutational profiles of neoplasms confirms their independent origin. Thus, a new case of primary multiple tumors is presented and possible ways of their formation with the participation of congenital disorders of the DNA mismatch repair system are suggested.