For a long time, ethical issues related to preconception genetic testing have been associated primarily with prevention programs for a limited number of hereditary diseases in specific regions of the world. The prospect of introducing preconception genetic screening into healthcare systems brings to light a complex set of ethical challenges, including providing comprehensive information to prospective parents, ensuring their truly informed decision-making, preventing discrimination, and drawing upon the accumulated experience of medical genetics. Sociocultural factors are particularly important in this context, as they influence the decision-making process regarding testing, shape social perceptions of risk, and affect individuals’ willingness to make choices based on information received from medical geneticists.

Heat shock proteins, which perform the functions of chaperones, contribute to the process of de novo folding of synthesized proteins and refolding of denatured proteins. It has been shown that mutagens formaldehyde, sodium azide, and potassium bichromate cause disturbances in protein structures, which was recorded by the luminescence of biosensors based on the E. coli strain K12 MG1655, which luminesce in response to the appearance of structurally disturbed proteins in the cell.

Diffuse leiomyomatosis is a rare disorder that is associated with X-linked Alport syndrome in most cases. The prevalence of X-linked Alport syndrome with diffuse leiomyomatosis is unknown (less than 50 clinical cases have been published to date). The disease is resulting from contiguous deletions of COL4A5 and COL4A6. Therefore, the clinical manifestations and prognosis of patients are determined by the combination of X-linked Alport syndrome and leiomyomatosis. We describe the case of Caucasian female patient with a lifelong history of microhematuria and persistent cough and dysphagia that developed at age 9. A chest Х-ray revealed mediastinal mass. A computed tomography scan of the chest and abdomen and esophagoduodenoscopy showed marked irregular parietal thickening of the esophagus and cardia with dilatation of the upper regions of the esophagus corresponding to diagnosis of diffuse leiomyomatosis. No indications for surgical intervention of leiomiomatosis were identified. The Alport syndrome genes panel was negative. Whole genome sequencing has revealed contiguous deletions of genes COL4A5 and COL4A6. The patient had albuminuria; no sensorineural hearing loss was detected. Herein, we highlight the importance of genetic testing to determine the management (including multidisciplinary approach) and prognosis (including familial) of the patient, as well as the need for an individual approach to the choice of genetic method.

HPV types of high oncogenic risk are recognized as the cause of cervical cancer. The literature notes differences in the expression of certain lncRNAs in cells affected by HPV-associated cancer compared with uninfected ones, which makes them potentially good markers for predicting cancer development. The aim of the study was to evaluate the level of transcription of the DINO and HOST2 lncRNAs genes in epithelial cells of the cervical canal of women with HPV infection with a clinically significant viral load. RT-PCR was used to obtain data on the relative expression levels of DINO and HOST2 in the women cells in two groups (HPV infected and control group). The relative level of the lncRNAs transcription is the same in these groups of cells. A direct correlation was found between the expression levels of HOST2 and DINO. It was found that the expression levels of DINO and HOST2 lncRNAs correlate with the mRNA levels of protein-coding genes TP53 and TP73 under high viral load.

Since 2023, the Russian Federation (RF) has been conducting newborn screening (NBS) for 36 hereditary diseases, including spinal muscular atrophy 5q (SMA 5q). As a result of expanded neonatal screening in 2023-2024, the total incidence of SMA 5q was 1 in 8,439 newborns.

The study was carried out on representative samples of Oirats from 14 populations in the Russian Federation, Kyrgyzstan, and Mongolia, collected in 2013-2017. The blood of 454 men served as material for the study of the Oirat gene pool, and 80 samples were genotyped using Illumina Omni Express v1.2 kits. The anthropological study sample was 1057 people (548 females and 509 males). Interpopulation distances for all studied systems (genetic, ethnoanthropological, anthropometric) and further calculation of pairwise closeness of distance matrices – multivariate generalisation of Pearson’s quadratic correlation coefficient – were used for comparison of genetic and anthropological data. Stable genophenotypic relationships between the applied genetic systems and anthropometric data of men and women were established, which indicates the stability of these relationships. Male anthropometric data are more strongly correlated with the genetic systems, with the strongest correlations showing transverse dimensions (0.81; 0.71; 0.72), skeletal proportions (0.73; 0.75; 0.52), followed by longitudinal dimensions (0.69; 0.62; 0.79) and girth dimensions (0.66; 0.70; 0.69). Such correlations are in favour of the applicability of anthropometric data in population studies and are suggested for introduction in the study of genetic diversity of the population.

Familial dysbetalipoproteinemia (FD) is a prevalent and highly atherogenic genetically based hyperlipidemia. The aim was to evaluate genetic drivers, contributing to FD using genetic data, n=4594. 24 lipid-related genes and 40 variants included in the hypertriglyceridemia genetic risk score were analyzed by NGS. The genetic basis of FD was identified in 67 patients, for 76.1% of whom was established FD. The autosomal recessive form contributed 74.5%, and the autosomal dominant FD was predominated by the carriage of APOE p.Arg154Cys (61.5%). In addition, 13.7% of FD patients were carriers of two or more causal variants in lipid-related genes (3 carriers of ε2ε1 APOE, 2 – of ε2ε2/LDLR, 1 – of ε2ε2/LPL, 1 – of p.Arg154Cys and compound heterozygous for two LPL variants). Polygenic hypertriglyceridemia was found in 41.7% of FD patients. The results demonstrate the diversity of genetic drivers in the overall structure of FD.

The trisomy 21 syndrome is one of the most common chromosomal diseases. Prenatal testing play an important role in diagnosing trisomy 21. Each stage of prenatal screening has its own limitations. This work demonstrates the challenges of diagnosis using first trimester screening, noninvasive prenatal test (NIPT), and invasive prenatal testing (IPT). The medical documentation of 29 children with diagnosed trisomy 21 was analyzed. First-trimester screening was conducted in 25 cases, with a high risk identified for 13 fetuses. NIPT was conducted in 10 cases, and high risk was identified in 9 cases. Ultrasound signs of fetal defects were detected in 24 cases. IPT was performed in 8 cases, and in three of them, trisomy 21 was not detected using the cytogenetic method on a chorionic villus sample. Thus, the most informative method was NIPT. Optimization of the use of laboratory methods and the timing of invasive diagnostics is required.

DNA methylation is one of the key mechanisms for controlling the individual development program of an organism. Disruption of this program can be associated with lethal effects during embryogenesis. The aim of the study was to analyze genome-wide methylation disorders in the fetal part of the placenta in cases of pregnancy loss. Genome-wide methylation profiles were analyzed from chorionic villi of spontaneous abortions with a normal karyotype (n = 7) and induced abortions (n = 7). Methylation profiles were obtained using reduced representation bisulfite sequencing (RRBS). Differential methylation of these regions is explained by both insufficient demethylation during reprogramming at the cleavage stage and insufficient methylation when establishing tissue-specific methylation patterns in the fetal part of the placenta.

The increasing incidence of obesity among the younger generation is one of the key problems of modern society, while the genetic factor is considered as a likely prerequisite for the development of this disease. Analysis of polymorphic variants of the PPARG, FABP2, ADRB2, and ADRB3 genes in 258 respondents showed a predominance of the frequency of the rs1042713 risk allele of the ADRB2 gene in the study sample, which may indicate its possible association with the development of obesity among children and adolescents.

Allergic diseases (AD) are common diseases of multifactorial nature. MicroRNAs play an important role in the AD pathogenesis by regulating the expression of inflammation and immune response-related genes and therefore appear to a promising marker of AD. The selection of gene polymorphisms was based on a thorough analysis of more than 6000 miRNA binding sites polymorphisms in genes involved in AD pathogenesis found in the miRNASNP and MIRDB databases. The aim of the study was the association analysis of polymorphisms in microRNA target sites of IKZF3 (rs907091), HLA-G (rs1063320) and VDR (rs739837) genes with upper respiratory tract AD in individuals of different ethnicity. The rs907091*T allele was associated with asthma and asthma with combined allergic rhinitis (AR) in Russians. The rs1063320*CC genotype was associated with asthma with combined AR in Russians, while the rs1063320*GC genotype was associated with asthma in Tatars. The results of the study suggest a definite role of IKZF3 and HLA-G genes in the AD pathogenesis.

Alternative splicing of mRNA (AS) is a key stage of gene expression post-transcriptional regulation, ensuring the various RNA isoforms expression. This mechanism plays an important role in the placenta development and function. The study focuses on decidual cells, which play a crucial role in both maintaining physiological pregnancy and the obstetric complications development. The research involved deep whole transcriptome sequencing with a detailed analysis of AS events in placental tissue under physiological pregnancy and fetal growth restriction. In decidual cells with fetal growth restriction, 8770 AS events were identified for 5411 genes, whereas in physiological pregnancy, 6489 events were detected for 4195 genes, suggesting a broader AS landscape in the disease. The analysis of differential AS between groups identified 51 genes involved in the fibroblast growth factor and Wnt signaling pathways, whose disruption may contribute to the fetal growth restriction development, as they play a crucial role in maintaining physiological pregnancy.

Background. Pharmacogenetic studies provide an opportunity to identify accurate predictors of individual responses to antidepressants, which potentially allows personalizing treatment for each specific patient.

Aim: to analyze the association of the rs6295 polymorphism of the HTR1A gene with the efficacy and safety of the selective serotonin inhibitor (SSRI) sertraline in patients with mixed anxiety-depressive disorder from the Republic of Bashkortostan.

Methods. The study included 100 patients taking sertraline for 6 weeks. The efficacy of therapy was assessed using the MontgomeryAsberg MADRS scale, the Clinical Global Impression scale CGI, and the side effect assessment scale UKU.

Results. The severity of depressive symptoms according to the scales and the severity of adverse reactions were statistically significantly higher in carriers of the rs6295*G/G genotype.

Conclusions. Polymorphic variants of the HTR1A gene may be predictors of response to SSRIs.

The aim of the study was to investigate the clinical and genetic features of diseases in patients with different types of leukodystrophies in Yakutia. The material for the study was the data from the Registry of Hereditary and Congenital Pathology of the Medical and Genetic Center of the Republican Hospital № 1-National Center of Medicine named after M.E. Nikolaev» and the Research Laboratory «Molecular Medicine and Human Genetics» of the Medical Institute of the NEFU. A total of 4 types of leukodystrophies were registered for the period from 2001 to 2024: hypomyelinating leukodystrophy type 7 with / without oligodontia and with / without gonadotropic hypogonadism – 1, adrenoleukodystrophy – 2, metachromatic leukodystrophy – 1, leukodystrophy with acquired microcephaly with / without dystonia – 5 cases from 4 families. All diseases, except leukodystrophy with acquired microcephaly with/without dystonia, manifest in childhood, and are characterized by a progressive course with various neurological manifestations. Further population and genetic-demographic studies are needed to develop disease prevention measures in the region.

In Krasnodar region neonatal screening (NS) for congenital hypothyroidism (CH) has been carried out since 1994; blood sampling from children was carried out on days 4-5 of life. It was of interest to evaluate the effectiveness of NS on CH in connection with the transition to early blood sampling in newborns. 101,445 children born from 1/1/23 to 12/31/24 were examined for CH: at the age of the first 2 days of life (group 1) – 93,431 (92.1%), at the age of 3-14 days of life (group 2) – 8,014 (7.9%). The threshold blood TSH level for children in group 1 was 10.2 µIU/ml, in group 2 – 8.52 µIU/ml. The average blood TSH level in group 1 was 3.23+3.4 µIU/ml, in group 2 – 2.15+5.4 µIU/ml.An increase in primary hyperthyrotropinemia was noticed in 2023-2024: 1.29% in group 1 and 1.49% in group 2. CH was diagnosed in 45 newborns (1:2254 newborns).Analysis of the results of NS on VH showed an increase in the threshold blood TSH level when examining children in the first 24-48 hours of life compared to the threshold TSH level during a later examination. Thus, changing the timing of examination of newborns during NS requires careful consideration of TSH threshold levels to prevent unnecessary retests.

The SLC26A4 gene is one of the most significant in the etiology of hereditary forms of hearing loss in many populations of the world. Currently, about 600 pathogenic SLC26A4 variants are known and, apparently, at least 25% of them lead to aberrant splicing. This study presents the results of an experimental in vitro analysis of the effect on splicing of several rare variants of the SLC26A4 gene identified in patients with hearing loss from the Republics of Tyva and Altai (Southern Siberia), using a minigene assay. The choice of these variants is due to the ambiguity of assessments obtained using bioinformatic prognostic programs. The pathogenic effect of the intronic variant c.2034+1G>A, leading to aberrant splicing, was experimentally confirmed. Functional analysis of the intronic variant c.1708- 18T>A showed that the acceptor site disruption and exon 16 skipping were observed only in a small proportion of transcripts with this variant, and three intronic variants c.1545-168A>G, c.1708-125T>C, c.1804-31C>T and the exon variant c.1545T>G did not affect the splicing process in the in vitro system. The obtained data emphasize the importance of an integrated approach to assessing the effects of genetic variants, combining in silico predictions with in vitro functional analysis, which is necessary for the correct interpretation of the identified genetic variations and accurate molecular genetic diagnosis.

The aim of the study was to investigate the relationship between the sputum microbiome composition and the level of chromosome damage in blood leukocytes of lung cancer patients. The bacterial microbiome composition of sputum, as well as the frequencies of chromosomal aberrations in blood leukocytes of 150 patients diagnosed with lung cancer and 104 healthy donors were studied. The results of NGS sequencing of the V3-V4 amplicon of the 16S rRNA gene showed that the sputum of lung cancer patients has signs of dysbiosis with a simultaneous increase in the content of bacteria of the genus Streptococcus. In patients with lung cancer and in the control, a direct relationship was found between the frequency of aberrant metaphases in lymphocytes and the content of representatives of the genus Streptobacillus in sputum. Only in patients were there positive correlations between the frequency of chromosomal aberrations and the content of bacteria of the phylum Fusobacteria, the genera Bacteroides and Leptotrichia. The results obtained indicate the presence of a genotoxic effect of a number of bacteria inhabiting the human respiratory tract. Future studies should be aimed at identifying the clastogenic potential of bacteria within the gut microbiome of colorectal cancer patients.

Introduction. The isonymy method is a cost-effective tool in population genetics, particularly valuable when molecular-genetic data are lacking. It allows for the assessment of inbreeding levels, migration patterns, and population structure using surname distribution.

Objective. To describe the theoretical and applied aspects of the isonymy method in studying Russian populations, and to demonstrate its utility in modeling the prevalence of hereditary diseases.

Methods. Electoral registers were used to calculate surname frequencies and random inbreeding coefficients. Additional tools included Barrai parameters (entropy, migration index), cartographic analysis, and cluster analysis using the McKusick arccosine metric.

Results. Significant correlations were found between random inbreeding values and the genetic burden of hereditary diseases. Family landscape schemes revealed ethnic structures, elementary population boundaries, and migration vectors.

Conclusion. The isonymy method enables large-scale demographic and genetic screening, helping to identify regions at higher risk for hereditary pathologies and to characterize complex population structures, including polyethnicity and migration patterns.

Statistical analysis of complete galactose level was carried out in blood samples of full-term newborns. Samples were obtained on the 4th day of life from children born in 2022 and on the first or second day of life from children born in 2023. The analysis showed (indicated) 17-fold decrease in high-risk group at the first step of galactosemia screening in 2023 compared to 2022. To increase the effciciency of newborn galactosemia screening an algorithm of optimization with second-level test was suggested. Determination of activity of galactose-1-phosphate uridyltransferase (GALT) enzyme allows to detect galactosemia type I regardless from reaching a critical level of galactose.

The aim of this study was to investigate the relationship between five polymorphisms identified by genome-wide association studies as susceptibility loci for arterial hypertension and the risk of developing peripheral artery disease (PAD). The rs7129220 locus in the AMPD3 gene was found to be associated with an increased risk of PAD (OR = 7.584; 95% CI: 1.89-30.33; Pperm=0.0001), regardless of gender. The polymorphism rs4373814 in the CACNB2 gene exhibited a statistically significant negative correlation with the ankle-brachial index (β=-0.053; Pperm=0.03). Additionally, SNP rs932764 in the PLCE1 gene was associated with elevated levels of low-density lipoprotein cholesterol (β=0.211; Pperm=0.03) and triglycerides (β=0.048; Pperm=0.04) in the plasma of patients with PAD. These findings suggest potential pleiotropic effects of genes involved in blood pressure regulation on other phenotypes related to atherosclerosis.

Algorithm for assessing the generic pesticide equivalence to original products based on the «mutagenicity» criterion, developed taking into account national characteristics in the field of pesticide handling, as well as examples of algorithm testing are described. To increase the sensitivity of the Ames test and overcome the cytotoxicity of substances from the sulfonylureas and triazolopyrimidines classes, new strains of S. typhimurium were obtained and an optimized testing protocol was developed. The data on the assessment of individual sensitivity to the genotoxic effect of pesticides in a model system on human lymphocytes are presented, indicating the need to take into account the sensitivity of cells from different donors when assessing mutagenicity in vitro.

Currently, as a result of the active processes of migration and assimilation, the transformation of the structure of the gene pools of the indigenous peoples of the world is being recorded, which in turn can lead to a change in the structure of morbidity. New data have been obtained regarding polymorphic variants of the vitamin D receptor genes VDR rs1544410, rs7968585, rs731236, rs2228570, rs3847987, rs79752 and vitamin-D binding protein GC rs7041, rs4588, rs375596 in local ethnic groups of Siberian Tatars in the Tomsk region. A specific genetic structure has been identified, characterized by polymorphic variants of genes encoding proteins with increased ability to bind and retain vitamin D in conditions of vitamin D deficiency.

Background. The protein MuRF1 is encoded by the TRIM63 gene and is a component of the ubiquitin-proteasome protein degradation system in cardiomyocytes. Recently, an autosomal recessive form of hypertrophic cardiomyopathy (HCM) has been identified in the context of mutations in TRIM63 [1]. Currently, there are no studies utilizing cardiogenically differentiated induced pluripotent stem cellderived cardiomyocytes (iPSC-CMs) that focus on TRIM63 mutations.

Objective. To identify potential nexus in the molecular pathogenesis of cardiomyopathy associated with the TRIM63 mutation.

 Patients and methods. Experiments were conducted on cardiomyocytes differentiated from induced pluripotent stem cells (iPSCs) obtained from a 19-year-old patient with HCM due to compound-heterozygous TRIM63 variants (C39G и S161CfsTer8) [2]. The study of calcium dynamics was conducted under conditions of electrical and chemical stimulation using the fluorescent probes Fura-2AM and Fluo-4AM.

Results. During electrical stimulation of iPSC-derived cardiomyocytes with the TRIM63 mutation, a 57% increase in the calcium transient duration was observed, accompanied by a 27% reduction in calcium release rate compared to donor cardiomyocytes. The peak release rate was reached significantly later than in healthy cells. Additionally, a significant increase in calcium influx amplitude due to storeoperated entry was noted, showing a 67% enhancement.

Conclusion. In the context of TRIM63-associated hypertrophic cardiomyopathy, alterations in physiologically important cellular processes were observed. The increase in the time to reach peak calcium release rate may indicate a delay in calcium release from the sarcoplasmic reticulum, as evidenced by the parameter measuring the time to 10% of the peak. It is suggested that the sarcoplasmic reticulum exhibits unregulated calcium uptake, its retention, and consequently, calcium overload.

Chronic obstructive pulmonary disease (COPD) is a multifactorial heterogeneous chronic inflammatory disease that affects distal airways (bronchi and bronchioles) and lung parenchyma and leads to pulmonary emphysema. We investigated the expression levels of selected genes in peripheral blood mononuclear cells (PBMCs) and lung tissue from patients with COPD: lncRNAs – TP53TG1, LINC00342, H19, MALAT1, DNM3OS, MEG3, LUCAT1, CDKN2B-AS1, SNHG5, miRNAs – miR-18a-5p, miR-200a-3p, miR-34a-5p, miR-126-3p, miR-218-5p, miR29a-3p, miR-150-5p, miR-570-3p, miR-155-5p, miR-15b-5p, miR-141-3p, miR-379-5p. Lung tissue and blood samples were collected from 141 patients and 138 healthy controls. Gene expression levels were analyzed by RT-qPCR. Our study identified significant differential expression in PBMCs 5 lncRNAs MALAT1, TP53TG1, LINC00342, DNM3OS, LUCAT1; 9 miRNAs: miR-155-5p, miR-141-3p, miR-379-5p, miR18a-5p, miR-34a-5p, miR-126-3p, miR-218-5p, miR-29a-3p, miR-150-5p. In lung tissue significant expression changes were observed in 4 lncRNAs: LUCAT1, CDKN2B-AS1, DNM3OS, TP53TG1; 7 miRNAs: miR-155-5p, miR-15b-5p, miR-18a-5p, miR-200a-3p, miR-34a-5p, miR126-3p, miR-218-5p. In silico pathway enrichment analysis indicates that RNAs differentially expressed in COPD patients are implicated in critical cellular processes, including apoptosis, antioxidant response, inflammation, and cellular senescence.

Most patients with Classical Phenylketonuria older than 16 years old, havehigh levels of serum phenylalanine. It is related to the difficulty in following to a low-phenylalanine diet. In these cases, it is leading to the development of complications. According to literary sources, the prevalence of intellectual disability, anxiety disorders, and depression in patients over 16 years old with Phenylketonuria is higher than in the general population. In this way, the appointment of enzyme replacement therapy is an optimal solution for the treatment in this group of patients. The analysis of the results of the use of enzyme replacement therapy in patients of the Russian Federation with an established diagnosis of classical phenylketonuria according to the clinical register of phenylketonuria/hyperphenylalaninemia (PKU/HFA) is presented in the article.

Relevance. Acute cerebrovascular accident (ACVA) in severe preeclampsia (PE) during pregnancy is recognized as a severe complication of pregnancy, childbirth, and the postpartum period, leading to increased maternal and perinatal morbidity and mortality.

Objective. To study the associations of 20 polymorphic loci of genes involved in coagulation and fibrinolysis, angiogenesis and endothelial dysfunction, immune response, lipid metabolism, and GWAS-associated loci with the risk of developing ACVA in severe PE. Methods. A DNA study was conducted on 103 Kazakhstani female patients with ACVA in PE (40 of whom (38.8%) had a fatal outcome) and 104 Kazakhstani women with severe PE in the comparison group. Genotyping of polymorphic loci was performed using real-time polymerase chain reaction.

Results. Significant associations (р<0.05) were identified for genotypes of five gene polymorphisms: coagulation (FV, FII); angiogenesis and endothelial dysfunction (PGF); immune response (TLR4, PLECHA1), with a high risk of developing ACVA in PE. The presence of an unfavorable heterozygous or homozygous genotype increases the risk of developing acute cerebrovascular accident in severe preeclampsia during pregnancy by 3.5 to 8.4 times.

Conclusion. The identified genetic associations enable the prediction of the development and severity of ACVA in PE, the formation of high-risk groups, the prevention of disease progression, and the personalization of therapy to prevent adverse outcomes for both mother and fetus.