The main hypothesis of carcino-evo-devo theory posits that hereditary tumors provide evolving multicellular organisms with extra cell masses for expression of evolutionarily new genes, which originate in DNA of germ cells. As a result of expression of novel genes and gene combinations, tumor cells acquire new functions and differentiate in new directions, which may lead to the origin of new cell types, tissues and organs. Several non-trivial predictions have been confirmed in our laboratory. In 1987, when only a dozen oncogenes have been described, I predicted that the number of oncogenes should correspond to the number of differentiated cell types in multicellular organism, two hundred cell types in humans at that time. Indeed, by now over two hundred different oncogenes have been described. Using computer genomics we confirmed the prediction about co-evolution of oncogenes, tumor suppressor and differentiation gene classes. Expression of evolutionarily new genes in tumors has been studied in many our publications. We described a new class of genes - tumor specifically expressed, evolutionarily novel (TSEEN) genes. The possibility of tumor participation in formation of new organs was confirmed on the model of «hoods» of goldfishes. We proved that «hoods» are benign tumors, the first example of artificial selection of tumors in the literature. Using the model of transgenic inducible tumors in fishes we have shown that human orthologs of fish TSEEN genes acquire progressive functions not encountered in fishes. This is a direct confirmation of the main hypothesis.

Background. In recent decades, special attention in the study of schizophrenia has been paid to the features of emotion recognition and the influence of both genetic and environmental factors on the development of the individual and the risk of developing mental illness. There is an assumption that disorders of emotion recognition are one of the endophenotypes of the disease. The important role of the violation of social cognitions, and in particular the recognition of emotions, in the social adaptation of patients with schizophrenia has been established. Establishing the role of genetic and environmental risk factors for schizophrenia in these disorders is an important step towards the formation of therapeutic approaches to their correction. Aim - to assess the contribution of the rs1344706 polymorphism of the ZNF804A gene and an unfavorable environment in childhood (the presence of alcoholism in the parental family) to the recognition of emotions in patients. Methods. The sample consisted of 854 patients divided into two groups: with alcoholism in the parental family and without it. To assess the recognition of mimic expression of emotions, photographs of six basic and three social emotions were used. Genotyping was performed by the HRM method. Results. An interaction effect between the genetic variant ZNF804A (rs1344706) and alcohol abuse by one of the proband’s parents on impairment of emotion recognition was found (p=0.02). Patients with the AA genotype were worse at recognizing emotions than those with the CC genotype. Conclusion. The results suggest an important role for the interaction of neurodevelopmentally associated schizophrenia risk genes and early environmental stressors in social cognition anomalies in schizophrenia.

Asthma is a complex,multifactorial and heterogenic inflammatory disease of the airways, associated withan imbalance between pro-inflammatory and anti-inflammatory cytokines and characterized by genetic determinism. Most patients with severe asthma are classified as T2-endotypeand have eosinophilic inflammation in the mucosa of the lower respiratory tract. The aim of the study was to analyze the distribution of genotypes IL4 rs2243250, IL5 rs2069812, IL13 rs1800925 in children with different phenotypes of bronchial asthma. Genotyping of polymorphisms was performedusing RT-PCR. The frequency of the TT genotype and the T allele rs1800925 IL13 has been shown to be significantly higher in patients with the eosinophilic asthma phenotype compared with a control group of healthy children (p<0,05).

The aim of the study was searching for miRNAs that are secreted by adipose tissue (AT) and could act as potential biomarkers of AT dysfunction and the development of concomitant pathologies in obesity. At the first step, miRNA profiling of extracellular vesicles from cultivated ex vivo adipose tissue was carried out in two groups of individuals: obese and non-obese. The next step included analysis of AT expression levels of the main target genes for microRNAs, which showed variation of their content in AT extracellular vesicles, this analysis was carried out in extended sample group of patients with obesity, including those with type 2 diabetes mellitus (DM2), and in the control group. The study has identified microRNAs (hsa-miR-145-5p and hsa-miR-302d-3p), that are associated with a decrease in the expression of key genes of lipid and glucose metabolism - PPARG, SLC2A4 - in AT of patients with obesity and DM2.

Background. Schizophrenia is characterized by a significant heterogeneity of symptoms. This fully applies to negative symptoms (NS), the heterogeneity of which, according to modern concepts, is determined by various neurobiological mechanisms. A widespread model of NS provides two factors (subdomains) in the structure of NS: abulia-apathy (AA) and expressive deficit (ED). Immunological studies have shown that the concentration of the pro-inflammatory cytokine TNF-α is differentially associated with NS subdomains. Objective. To investigate the relationship between NS factors and the TNF-α polymorphism rs1800629G/A. Methods. The sample for genotyping included 541 people. The severity of NS was determined by the Positive and negative syndromes scale (PANSS). PANSS symptoms were included into subdomains in accordance with the previously proposed approach. Genotypes were determined by PCR. Results. Differences in the severity of symptoms of the ED factor depending on the genetic variant rs1800629 were revealed (p=0.035). In patients with two copies of the A allele, which has a higher transcriptional activity, the severity of ED symptoms was higher than in the G allele carriers (22.8±4.7 versus 19.2±5.9 points). No significant effect of genotype on factor AA was found. Conclusion. The discovery of a differentiated relationship between TNF-α rs1800629 polymorphism and NS is consistent with the data of immunological studies, and also confirms the assumption of various biological mechanisms that determine the heterogeneity of schizophrenia NS.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, accounting for approximately one-third of hospitalizations for heart rhythm disorders. AF is associated with an increased risk of death, stroke and other thromboembolic complications, impaired quality of life, decreased exercise tolerance, and left ventricular dysfunction. Laboratory diagnosis of predisposition to the occurrence of thromboembolic complications is carried out by determining the polymorphism of genes of hemostasis factors. Of particular interest is the identification of cases of congenital thrombophilia resulting from molecular defects in the hemostasis system or its inhibition processes. The study included 41 healthy volunteers aged 53.4 ± 1.25 years and 52 patients with AF: paroxysmal and persistent forms at the age of 60.20 ± 1.73. Of these, 8 patients (15.38%) developed thromboembolic complications against the background of adequate anticoagulant therapy. Genetic methods of investigation included DNA isolation and examination of polymorphic variants of genes of the hemostasis system and platelet receptors using real-time polymerase chain reaction method. Comparative analysis of hemostasis system factors genotypes: rs1799963 FII, rs6025 FV, rs1800790 FGB, rs1799899 PAI-1 and platelet receptors: rs1126643 ITGA2, rs5918 ITGB3 in patients with atrial fibrillation and controls showed no significant differences. The studied genetic polymorphisms of hemostasis system factors and platelet receptors were not associated with the risk of thromboembolic complications in patients with atrial fibrillation.

Currently, the type of course of schizophrenia is a key feature in the classification of the disease. In this work, associations of polymorphic variants of the SLC1A2 gene with this trait were studied. Glutamate is the main excitatory neurotransmitter in the central nervous system. The SLC1A2 gene encodes EAAT2, one of the excitatory amino acid transporters (EAATs) that potentially influence glutamatergic neurotransmission by removing excess glutamate from the synaptic cleft. The study group included 655 patients with schizophrenia, 2 subgroups were identified: a subgroup of 398 patients with a continuous course of schizophrenia and a subgroup of 257 patients with episodic schizophrenia. Genotyping of 11 polymorphic variants of the SLC1A2 gene was carried out. It was found that the CT genotype and the C allele rs1042113 SLC1A2, as well as the CT genotype rs12294045 SLC1A2, were associated with the continuous course of schizophrenia. Thus, the present study showed the involvement of the SLC1A2 gene in determining the type of course of schizophrenia.

Tardive or tardive dyskinesia is a severe motor side effect of antipsychotic drugs characterized by involuntary rapid muscle contractions and athetoid movements of the trunk, limbs, and orofacial muscles. The exact mechanism of tardive dyskinesia is still unknown. Glutamate is the main excitatory amino acid neurotransmitter in the mammalian central nervous system. The GRIN2A gene encodes the GluN2 subunit of the ionotropic glutamate receptor NMDA. The aim of this study was to investigate the association of polymorphic variants of the GRIN2A gene with tardive (tardive) dyskinesia in patients taking antipsychotic drugs. 944 patients with schizophrenia were examined (435 women and 509 men), Tardive dyskinesia was diagnosed in 229 patients. Genotyping of 12 polymorphic variants of the GRIN2A gene was carried out. The results of the associative analysis showed that the polymorphic variant rs8057394 is associated with tardive dyskinesia. rs7206256 of the GRIN2A gene showed an association with the orofacial form of dyskinesia. It was also found that the GG genotype and the G allele rs7192557 of the GRIN2A gene have a protective effect against the development of the limbthoracic type of tardive dyskinesia. Thus, it was possible to confirm the hypothesis about the association of the GRIN2A gene with antipsychotic-induced tardive dyskinesia in patients with schizophrenia.

Aim: to analyze the structure of congenital malformations (CM) of the central nervous system (CNS) in fetuses for the period 2017-2021. Pregnant women underwent ultrasound examination of the fetus (ultrasound) as part of early prenatal screening of the first trimester (RPS) at 11-13.6 weeks of gestation, ultrasound of the second and third trimesters - at 19-21 and 30-34 weeks of gestation, respectively. For the period from 2017 to 2021, a total of 1585 cases of CM in fetuses were detected in various organs and systems. During the same period, the share of CNS CM in fetus of various nosological groups was 17.09%, 13% CNS CM were found in the first trimester, in the second and third trimesters - 48% and 39%, respectively. During the study period the frequency of detection of CNS CM varied from 17.7% in 2017 to 21.7% in 2019. All pregnant women with fetal CNS malformations were offered invasive dagnostics, 26.19% of patients agreed to an invasive procedure. In 84.6% of fetuses with CNS pathology, no numerical and visible structural chromosome disorders were detected (a normal karyotype was established). Chromosomal pathology in fetuses was detected in 15.4% cases: trisomy of chromosome 21 (2.8%); trisomy of chromosome 18 (1.4%); trisomy of chromosome 13 (1.4%); trisomy of chromosome 9 (1.4%); triploidy (1.4%); partial monosomy of the long arm of chromosome 21 and partial monosomy of the long arm of chromosome 3 (4.22%); translocation between chromosomes 10 and 20 (1.4%), partial monosomy 1q21.1-1.4%. Of this amount, 35% percent of pregnancies were terminated by family decision.

Inhaled glucocorticosteroids (GCS) are one of the most commonly used groups of anti-inflammatory drugs prescribed to asthma treatment. The aim of this work has been to perform a meta-analysis of the associations of polymorphic variants of genes involved in GCS metabolism or associated with sensitivity to GCS treatment according to GWAS with asthma development, age of manifestation and severity in individuals of Russian, Tatar, and Bashkir ethnicity. DNA samples of 846 of asthma patients and controls aged 3 to 67 years from the Republic of Bashkortostan have been used in the study. A meta-analysis of the associations of 10 polymorphic variants of studied genes with asthma development and clinical course severity in individuals of Russian, Tatar, and Bashkir ethnicity has been carried out. The associations of the rs10044254*T allele of the FBXL7 gene and the rs1876828*T allele of the CRHR1 gene with risk of asthma development, the rs10044254*T allele of the FBXL7 gene and the rs2395672*G allele of the CMTR1 gene with asthma manifestation in childhood, the rs1876828*T allele of the CRHR1 gene with severe and moderate asthma have been found.

We conducted a replicative associations analysis of the single-nucleotide polymorphisms of 8 most significant candidate genes of preeclampsia: rs1801133 in the MTHFR gene, rs1799963 in the F2 gene, rs6025 in the F5 gene, rs1799889 in the SERPINE1 gene, rs1799983 and VNTR in the NOS3 gene, rs3025000, rs3025010 and rs10434 in the VEGF gene, rs699 in the AGT gene, rs4646994 in the ACE gene. The results demonstrate а significant associations of preeclampsia with 5 SNP 6 genes: rs1799889 in the SERPINE1 gene and rs1799983 in the NOS3 gene in Buryats, Russians and Yakuts, VNTR in the NOS3 gene in Buryats, rs1801133 in the MTHFR gene, rs6025 in the F5 gene and rs3025010 in the VEGF gene in Russian.

The results of the study of microRNAs miR-221 and miR-223 in blood plasma microvesicles in patients with pulmonary embolism, as well as their relationship with clinical blood test parameters and the severity of complications, were presented.

Ficolins involved in the protecting from pathogenic microorganisms through the lectin pathway activation of the complement system. In current study data on the prevalence of genotypes and allelic variants for H-ficolin FCN3 rs532781899 in the ethnic groups of the Krasnoyarsk region (Nenets, Dolgan-Nganasans and Russians) were obtained. Genotyping was carried out using RT-PCR. The frequency of the variant del* FCN3 (+1637delC) rs532781899, leading to low concentration or complete absence of the activator of the lectin complement pathway, N-ficolin, namely, 3.6% among Russians and 0% in the Nenets, 0.8% in Dolgan-Nganasans was revealed.

In this work, the contribution of mitochondrial DNA (mtDNA) polymorphism to the predisposition to the development of type 1 diabetes (T1D) and its complications was studied. The study was conducted in a group of patients with T1D (n=396) and a population sample of residents of the Tomsk city (n=424). MtDNA polymorphism was studied by sequencing the hypervariable mtDNA D-loop segment and further classification of mtDNA haplotypes according to known haplogroups. The study revealed a protective effect of a rare haplogroup W with T1D (OR=0,28 (95% CI 0,09-0,85), p=0,03) and a risk effect of haplogroup T for the development of neuropathy in T1D (OR=1,72 (95% CI 1,04-2,87), p=0,048).

The study involved 559 miners living in the Kemerovo region of Russia were examined, including 236 patients with lung cancer and 323 without signs of oncological diseases. A comparative analysis of polymorphic variants of the MMP1 -1607insG (rs1799750) gene was carried out in miners with lung cancer and individuals without cancer living in the same area. Analysis of single-locus effects showed a significant relationship between the risk of lung cancer and the 2G/2G genotype of the MMP1 gene in the general group (OR = 1.55, CI: 1.08-2.21, p = 0.02) and the smoking group (OR= 2.08 95% CI: 2.08 1.20- 3.59, p=0.008). The 2G allele also showed a significant association with the risk of developing PD in miners in the general group (OR= 1.32 95% CI: 1.04-1.67, p=0.02) and the smoking group (OR= 1.63 95% CI: 1.16-2.31, p =0.005).

Preeclampsia (PE) occurs in 2-8% of pregnancies and is one of the most important causes of maternal and perinatal morbidity and mortality in the world. Numerous studies have demonstrated the key role of impaired placentation processes associated with pathological trophoblast invasion and reduced remodeling of myometrial spiral arteries in the development of PE. The molecular mechanisms and genetic factors behind this observation are still unclear. On the example of PE, we tested a systematic approach to the search for promising biomarkers of gestational complications, which is based on a combination of genomic, transcriptomic, and bioinformatic methods. This approach has demonstrated its effectiveness and made it possible to discover new genetic markers of PE, to reveal the significant role of regulatory regions of the human genome in susceptibility to this disease.

Numerous studies on genetic markers of osteoarthritis (OA) have been conducted over the past decades, but the molecular pathogenesis of the disease is still unclear. MicroRNA binding sites, which serve as an intermediate between genetic and epigenetic mechanisms, represent a promising new area of research. The aim of the study was to investigate the microRNA binding sites of target genes in women with OA taking according ethnicity. Material and Methods. The study enrolled 356 women (51.67±11.5 years) with OA and 161 age-matched women without joint pathology. The loci rs1061237, rs1061347 (COL1A1), rs9659030 (COL11A1), rs229069, rs229077, rs9978597 (ADAMTS5), rs5854, rs470215 (MMP1), rs1042840 (MMP13), rs1042673 (SOX9) rs13317 (FGFR1), rs4647940 (FGFRL1), rs73611720 (GDF5), rs6854081 (FGF2) were genotyped by competitive allele-specific PCR (KASP). Results. The C allele of the rs229069 and the T allele of the rs13317 were associated with OA in the total sample (OR=1.43 and OR=1.67). After Benjamin-Hochberg correction, rs13317 remained statistically significant (p<0,05). Considering ethnic heterogeneity, associations of the T allele (rs1061237) with OA in women of Russian origin (OR=1.77), the G allele (rs6854081) in women of Tatar origin (OR=4.78), the C allele (rs229069) and the T allele (rs73611720) in women of mixed and other ethnic groups (OR=2.25 and OR=3.02) were identified. All associations remained statistically significant after the Benjamin-Hochberg correction. Conclusions. Associations of polymorphic variants of FGFR2, FGF2, ADAMTS5 genes with osteoarthritis in different ethnic groups from Bashkortostan Republic were revealed.