Throughout their lives, cells synthesise new and dispose of the old, denatured proteins and insoluble protein aggregates. An important role in maintaining proteostasis is played by chaperones, which fold various proteins and promote degradation of denatured or misfolded proteins via proteasomes or autophagy. Despite protein folding being an accurate process, as organisms age and experience stress, errors accumulate, which leads to the formation of protein aggregates that can result in pathological changes. In addition, stress factors such as elevated temperature and altered pH can promote protein denaturation that can result in the proteins not only losing their native functions, but also gaining novel cytotoxic properties. With the increase of human average lifespan, more and more cases of proteinopathies – diseases caused by disruptions in proteostasis, e. g. Alzheimer’s disease, Huntington’s disease etc. – emerge. Therefore, identification of mechanisms preventing the formation of cytotoxic protein aggregates and promoting their clearance is of high importance. Heat shock proteins (HSPs) are the molecular chaperones involved in folding nascent proteins and refolding the denatured ones, leading to their reactivation. Heat shock proteins vary in structure and functions and are found in all prokaryotes and eukaryotes discovered to date. HSPs are constantly synthesised in cells under normal conditions, and a multitude of them are dramatically up-regulated during stress, which includes heat shock (which earned them their name) and metabolic stress caused by the increased numbers of misfolded proteins. In this review, we describe mechanisms of action and functions of members of five heat shock protein families.

   Parkinson’s disease is a neurodegenerative disorder affecting dopaminergic neurons of the substantia nigra pars compacta. The known pathological genetic variants may explain the cause of only 5 % of cases of the disease. In our study, we found two patients with a clinical diagnosis of Parkinson’s disease with the genetic va riant c.1087G>T (p.Gly363Cys) of the LGR4 gene. The LGR4 gene encodes the membrane receptor LGR4 (leucine rich repeat containing G protein-coupled receptor 4) associated with the G protein. We hypothesize that the LGR4 gene may be either a direct cause or a risk factor for this disease, since it is one of the main participants of the WNT/β-catenin signalling pathway. This signalling pathway is necessary for the proliferation of neurons during their differentiation, which may lead to Parkinson’s disease. To study the relationship between this genetic variant and Parkinson’s disease, an ideal tool is a cellular model based on induced pluripotent stem cells (iPSCs) and their differentiated derivatives, dopaminergic neurons. We reprogrammed the peripheral blood mononuclear cells of the two patients with the c.1087G>T variant of the LGR4 gene with non-integrating episomal vectors expressing OCT4, SOX2, KLF4, LIN28, L-MYC and mp53DD proteins. The obtained seven lines of induced pluripotent stem cells were characterised in detail. The iPSCs lines obtained meet all the requirements of pluripotent cells, namely, they stably proliferate, form colonies with a morphology characteristic of human pluripotent cells, have a normal diploid karyotype, express endogenous alkaline phosphatase and pluripotency markers (OCT4, NANOG, SSEA-4 and SOX2) and are capable to differentiate into derivatives of the three germ layers. The iPSC lines obtained in this work can be used as a tool to generate a relevant model to study the effect of the pathological variant c.1087G>T of the LGR4 gene on dopaminergic neuron differentiation.

   In pronuclear microinjection, the Cas9 endonuclease is employed to introduce in vivo DNA double-strand breaks at the genomic target locus or within the donor vector, thereby enhancing transgene integration. The manner by which Cas9 interacts with DNA repair factors during transgene end processing and integration is a topic of considerable interest and debate. In a previous study, we developed a barcode-based genetic system for the analysis of transgene recombination following pronuclear microinjection in mice. In this approach, the plasmid library is linearized with a restriction enzyme or a Cas9 RNP complex at the site between a pair of barcodes. A pool of barcoded molecules is injected into the pronucleus, resulting in the generation of multicopy concatemers. In the present report, we compared the effects of in vivo Cas9 cleavage (RNP+ experiment) and in vitro production of Cas9-linearized transgenes (RNP– experiment) on concatenation. In the RNP+ experiment, two transgenic single-copy embryos were identified. In the RNP– experiment, six positive embryos were identified, four of which exhibited low-copy concatemers. Next-generation sequencing (NGS) analysis of the barcodes revealed that 53 % of the barcoded ends had switched their initial library pairs, indicating the involvement of the homologous recombination pathway. Out of the 20 transgene-transgene junctions examined, 11 exhibited no mutations and were presumably generated through re-ligation of Cas9-induced blunt ends. The majority of mutated junctions harbored asymmetrical deletions of 2–4 nucleotides, which were attributed to Cas9 end trimming. These findings suggest that Cas9-bound DNA may present obstacles to concatenation. Conversely, clean DNA ends were observed to be joined in a manner similar to restriction-digested ends, albeit with distinctive asymmetry. Future experiments utilizing in vivo CRISPR/Cas cleavage will facilitate a deeper understanding of how CRISPR-endonucleases influence DNA repair processes.

   The widespread use of narrowleaf lupine (NLL, Lupinus angustifolius L.) as a feed and food crop requires source material for breeding cultivars with high-quality seeds. The priority criterion for attributing NLL cultivars to the feed or food category is the content of alkaloids. At the same time, equally important seed quality indicators are the protein and oil content, as well as moisture content, which determines the possibility of long-term storage of seeds. For the first time in Russian lupine science, an attempt was made to study the relationships between all the listed characteristics of narrowleaf lupine seeds under the conditions of Northwest Russia (Pushkin town). Sixty-two accessions from the VIR collection were studied in 2019, 2020 and 2022. The range of variability of the studied characteristics was 27.8–37.6 % for protein, 3.9–7.3 % for oil, 1.6–2017.4 mg/100 g of dry matter (D.M.) for alkaloids, and 6.4–7.3 % for moisture. A significant negative correlation between the oil and protein content (–0.33) was observed only in 2019. No significant correlations between the protein and alkaloid content were found in the studied sample. Significant negative relationships were identified between the content of oil and alkaloids only in 2019 and 2020 (–0.38 and –0.27, respectively). In 2022, no correlations were identified. Obviously, the identification of regularities in these correlations requires many years of research taking into account weather conditions. The influence of weather on the concentration of alkaloids in seeds has been proven. The average amount of alkaloids for the sample in 2019 was 504.2 ± 77.7 mg/100 g D.M., 263.7 ± 38.6 mg/100 g D.M. in 2020, and 319.8 ± 51.4 mg/100 g D.M. in 2022. It confirmed the data previously obtained by the authors that the content of alkaloids in seeds increases significantly along with the precipitation deficiency. The temperature regime during this research did not affect this indicator. An increased air temperature contributed to the accumulation of oil, and an increase in precipitation contributed to the accumulation of protein. The most stable indica-
tor independent of environmental conditions was the seed moisture. Accessions with the optimal combination of the main biochemical parameters that determine seed quality have been identified for breeding narrowleaf lupine cultivars in the region in question for feed and food purposes, as well as for green manure.

   The endocarp or stone is the most stable morphological feature of the genus Prunus. However, the identification of plum types, groups and/or genotypes based on endocarp is complicated because of a wide range of variation and morphological transitional states. From this point of view, knowledge on the degree of variability within and between plum species or cultivars is a sine qua non for taxonomists and also for pomologists. In this study, different endocarp morphological traits, such as SW, linear dimensions (L, W and T), D_a, D_g, S, V and shape indexes (φ, SI, E, RS, RO, DE and PI) were determined using analysis of variance and multivariate analysis (correlations and PCA). Results showed significant differences among accessions for all properties evaluated but with high overlaps in values. In most cases, the examined parameters were positively or negatively correlated with each other, indicating developmental relationships between them. Indeed, positive correlations were recorded for most variables, especially related to SW and endocarp linear dimensions. These results showed that the above properties could be a powerful indicator for selecting adequate endocarp size and shape in accessions, which may be used in taxonomic analysis. With an account of these correlations, PCA was employed to correctly estimate the endocarp size and shape and distribution, segregation and dispersion of accessions. All linear measurements and index values showed a normal or low variability at the individual level in most cases, with the exception of SW, V and PI in both European and Damson plums and S in Damson plums. Of the 15 examined parameters, European plum had significantly higher SW, L, T, D_a, D_g, S, E, RO and PI values than Damson plum. In contrast, Damson plum had higher SI, RS and DE values, while W, V and φ were similar.

   The content of hexoses (fructose, glucose) essential for the fruit of the tomato (Solanum lycopersicum L.) is regulated by the joint activity of sucrose hydrolysis enzymes (including invertases), invertase inhibitors, and sugar transporters. In addition to fruit taste, soluble sugars are closely related to the stress resistance of the tomato plant. In this work, we determined the diurnal dynamics of the content of soluble sugars (sucrose, fructose and glucose) and the expression of genes for sucrose hydrolysis enzymes (vacuolar invertase TAI, cell wall invertase LIN6) and the hexose transporter (STP1) in the leaves of the tomato variety Korneevsky. It was shown that both the amount of sugars and the level of transcripts of the TAI, LIN6 and STP1 genes depend on the circadian rhythm and correspond to the biological processes occurring in the plant at different periods of the day. The content of sucrose and hexoses changes in a similar way during the day. At the beginning of the light phase, the concentration of sugars is minimal, at the end it has the highest daily values; at the beginning of the dark phase, it shows a residual increase and then decreases towards the end of the phase. In silico analysis of organ-specific expression of TAI, LIN6 and STP1 in S. lycopersicum cv. Micro-Tom showed the presence of mRNA of all three genes in all tissues. The TAI gene was expressed most strongly in ripe fruits, while the level of LIN6 and STP1 transcripts was extremely low. The level of TAI mRNA in the leaves was ~2 times higher than that of LIN6 and ~27 times higher than that of STP1. Analysis using qRT-PCR of the diurnal dynamics of TAI, LIN6 and STP1 expression in the cv. Korneevsky leaves showed that all three genes were expressed at all points analyzed. Fluctuations in their expression levels occur in a similar manner: mRNA levels reach peak values in the middle of the light and dark phases. The results obtained are important for understanding the functions of invertases and sugar transporters in the tomato plant, and can be used in predicting the stress resistance of plants in tomato breeding.

   Chickpea is the second most important legume crop, which is used as a food by people in different parts of the world due to its high nutritive value. Omics technologies have revolutionized the characterization of chickpea genetic diversity by considering single-nucleotide polymorphisms, while structural variants and transposons have been overlooked. The specific contribution of transposons to the phenotypic diversification of crop species is still poorly documented, therefore its characterization is important. We focused on landraces collected before the “green revolution”, as they are a valuable source of species diversity and can be used to broaden the genetic base of modern cultivars. Analyzing 190 chickpea genomes, we found 42,324 new transposon insertion sites from 83 families and showed that such sites are highly polymorphic. Most insertions were caused by mobilization of retrotransposons (67 % of insertions); among DNA transposons, the highest number of insertions was found for the superfamilies MuDR, PIF, hAT, CMC, and TcMar. We also demonstrated an uneven distribution of insertion sites along chromosomes. Analysis of the localization of transposon insertion sites relative to genes and their structural elements has shown that the largest number of insertions in all transposon superfamilies falls on introns and the smallest, on exons. We also showed that transposon insertion sites, which until recently have been overlooked by population genomics, are an important factor that diversifies phenotypes and can be used in GWAS as markers replacing SNPs. Comparative analysis of landraces collected in different geographic regions showed that the Ethiopian accessions have many unique transposon insertion sites. Our results highlight the unique role of transposon mobilization in chickpea diversification and have important implications for breeding improved chickpea varieties adapted to global climate change.

   Arbuscular mycorrhizal fungi (AMF) play a key role in the regenerative successions of plant communities after anthropogenic disturbances, particularly in quarries. AMF help plants with water and mineral nutrition, contributing to the restoration rate of vegetation cover.

   The research is aimed to study the biodiversity of AMF using molecular genetic methods at different stages of overgrowth of two quarries in the Leningrad region.

   Molecular genetic identification of fungi was carried out using Illumina MiSeq analysis of the ITS1 and ITS2 regions as barcodes for the identification of operational taxonomic units (OTUs) with species-level identification. An adapted and error-checked AMF genetic sequence database from NCBI was used as a reference. The study applied an optimized nucleic acid isolation technique for sandy soils. The results showed maximum AMF biodiversity at the initial stages of overgrowth – pioneer and grass stages – with minimum diversity observed at the shrub stage, where it decreased by five times. At the forest stage, the biodiversity of AMF was almost restored to the level seen at the grass stage. It has been shown that the biodiversity and species composition of AMF can vary greatly between the stages of regenerative succession and probably depends primarily on the biodiversity of grasses, with which AMF most effectively enter into symbiotic relationships. The analysis showed a reliable negative correlation between the number of AMF species and the number of woody plant species. Such studies can aid in understanding how plant-fungal symbiosis develops in regenerative successions and which AMF most effectively contribute to vegetation cover restoration.

   Wolbachia pipientis is an α-proteobacterium, which is a widespread intracellular symbiont in a number of Arthropoda and some Nematoda species. With insects, W. pipientis forms a symbiont-host system characterized by very close interactions between its components. The mutual effects of Wolbachia on the host and the host on Wolbachia are important biotic factors for both components of this symbiotic system. Wolbachia is able to affect both host reproduction and somatic organ function. Due to its prevalence among insects and a wide variety of both negative (cytoplasmic incompatibility and androcide are among the most well-known examples) and positive (increasing resistance to biotic and abiotic factors, providing vitamins and metabolites) effects on the host organism, Wolbachia is of great interest for both entomologists and microbiologists. The diversity of host phenotypes induced by Wolbachia provides a broad choice of evolutionary strategies (such as reproductive parasitism or mutually beneficial symbiont-host relationships) that it utilizes. The influence of Wolbachia is to be considered in the design of any experiment conducted on insects. The application of sequencing technologies has led to new approaches being created to study the existing relationships within the Wolbachia-insect system, but interpretation of the data obtained is challenging. Nevertheless, the prospects for the use of the whole-genome analysis data to study Wolbachia-host coevolution are beyond doubt. Ongoing projects to introduce Wolbachia strains, which provide antiviral host defense, into insect populations to control the spread of RNA-viruses are actively pursued, which could result in saving many human lives.

   The aim of this brief review is to summarize the data collected by scientists over the past hundred years of Wolbachia studies and the current understanding of its genetic diversity and mechanisms of interaction with the host, including those based on transcriptome analysis.

   Our purpose was to model a combination of a prolonged consumption of ethanol with Opisthorchis felineus infection in mice. Four groups of C57BL/6 mice were compiled: OF, mice infected with O. felineus for 6 months; Eth, mice consuming 20 % ethanol; Eth+OF, mice subjected to both adverse factors; and CON, control mice not exposed to these factors. In the experimental mice, especially in Eth+OF, each treatment caused well-pronounced periductal and cholangio fibrosis, proliferation of bile ducts, and enlargement of areas of inflammatory infiltration in the liver parenchyma. Simultaneously with liver disintegration, the infectious factor caused – in the frontal cerebral cortex – the growth of pericellular edema (OF mice), which was attenuated by the administration of ethanol (Eth+OF mice). Changes in the levels of some proteins (Iba1, IL-1β, IL-6, and TNF) and in mRNA expression of genes Aif1, Il1b, Il6, and Tnf were found in the hippocampus and especially in the frontal cortex, implying region-specific neuroinflammation. Behavioral testing of mice showed that ethanol consumption influenced the behavior of Eth and Eth+OF mice in the forced swimming test and their startle reflex. In the open field test, more pronounced changes were observed in OF mice. In mice of all three experimental groups, especially in OF mice, a disturbance in the sense of smell was detected (fresh peppermint leaves). The results may reflect an abnormality of regulatory mechanisms of the central nervous system as a consequence of systemic inflammation under the combined action of prolonged alcohol consumption and helminth infection.

   Various genetic features of the hitman strain of the widespread parasitoid of Drosophilidae (Diptera), Pachycrepoideus vindemmiae (Rondani, 1875) (Pteromalidae, Pachyneurinae) were studied. This strain was established and is maintained at the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences (Novosibirsk, Russia). An analysis of air-dried chromosome preparations from prepupae of this parasitoid showed that it has n = 4 and 2n = 8 in males and females, respectively, which is the lowest known chromosome number in the family Pteromalidae. All chromosomes in the karyotype of this species are metacentric. The first and second chromosomes are of similar size, the remaining ones are substantially shorter. The same results were obtained for an additional strain of this species kept at the Moscow State University (Moscow, Russia). A comparison of the DNA sequence of the barcoding region of the mitochondrial cytochrome c oxidase (COI) gene of the hitman strain of P. vindemmiae with those available from the GenBank and BoLD databases demonstrated that this strain clustered together with conspecifics originating from China, Turkey and Italy. Despite certain endosymbionts being previously reported for the genus Pachycrepoideus Ashmead, 1904 as well as for P. vindemmiae itself, the hitman strain turned out to be free of endosymbiotic bacteria in the genera Arsenophonus Gherna et al., 1991, Cardinium Zchori-Fein et al., 2004, Rickettsia da Rocha-Lima, 1916, Spiroplasma Saglio et al., 1973 and Wolbachia Hertig, 1936. The above-mentioned results improve our knowledge of various genetic features of parasitoids of the family Pteromalidae and those of P. vindemmiae in particular.

   Russia has a significant pedigree diversity of horse breeds with unique gene pools that are well adapted to a wide variety of harsh natural and climatic conditions, are characterized by universal performance and high productive qualities, and are of significant interest to the world horse breeding. Genetic studies of population diversity in horse breeding are very relevant, since many domestic horse breeds are under threat of extinction. Biomaterials (hair, blood, semen) from horses of 15 local breeds bred in the Russian Federation and neighboring countries (CIS) were selected for the research. The sample included 2,193 horses, including: Altaiskaya (n = 48), Bashkirskaya (n = 130), Buryat skaya (n = 30), Vyatskaya (n = 220), Zabaikalskaya (n = 34), Kyrgyzskaya (n = 100), Mezenskaya (n = 148), Mugalzhar skaya (n = 109), Novoaltaiskaya (n = 514), Pechorskaya (n = 31), Shetland pony (n = 47), Priobskaya (n = 85), Tuvinskaya (n = 600), Khakasskaya (n = 47) and Yakutskaya (n = 50) breeds. The following indicators were used in the genetic and population analysis: the total number of allele variants (Na) in 17 microsatellite loci, the level of polymorphism (Ae), the average number of alleles per locus (Nv), observed (Ho) and expected (He) heterozygosity, coefficients of genetic similarity and genetic distances, as well as the coefficient of intrapopulation inbreeding (Fis). Modern local horse breeds, even relatively small in number, have a high level of biodiversity and a peculiar genetic structure, often with the presence of private alleles, which persists despite periodic crossing with stud breeds of different specializations. It was found that horses of local breeds possess a number of unique alleles, including ASB2T, HMS7S, HMS6J, HMS6H, HMS2T, HMS1O, HTG7L, HTG6L, HTG6H, VHL20S, ASB17Z, ASB17X, ASB17U, LEX3S, LEX3R and CA425E, which were not detected in representatives of stud breeds in the studied European populations. The majority of the studied breeds were characterized by a negative Fis value and the absence of inbreeding. The coefficients of genetic similarity of local breeds varied in a relatively wide range (0.828–0.973) and testified to the uniqueness of the gene pools of most local horse breeds of the Russian Federation, as well as confirmed the common origin of the Kyrgyzskaya horse with the horse populations of Southern Siberia.

   The Yaroslavl cattle is a native Russian dairy breed developed in the 19th century from the Northern Great Russian cattle, which were adapted to withstand harsh climates and poor forage conditions. Previous studies identified two breed-specific missense mutations in the MSS51 (Ala415Glu) and KAT6B (Val105Met) genes that negatively impact the body weight of the animals.

   This study aimed to confirm the association of these missense mutations in the MSS51 and KAT6B genes, along with the mutant haplotype containing both mutations, with live weight at various ages in the Yaroslavl breed using an expanded sample set.

   We genotyped 113 cows for these missense variants and analyzed their associations with live weight at birth, as well as at 6, 10, 12, 15, and 18 months in a combined sample of 143 animals, which includes earlier data. We employed linear regression and one-way ANOVA for statistical analysis. The results from linear regression indicated significant associations with live weight at 6, 12, and 18 months for the mutation in the KAT6B gene. The MSS51 gene mutation was associated with live weight at 6, 12, 15, and 18 months. Notably, the mutant haplotype was linked to live weight across all ages from 6 to 18 months. One-way ANOVA revealed significant associations of live weight with KAT6B genotypes only at 6 months. For the MSS51 gene mutation and the mutant haplotype, significant associations were found at 6, 12, 15, and 18 months. In both statistical tests, the most significant association was observed for the mutant haplotype rather than for the individual variants. These findings could be instrumental in enhancing the live weight of beef hybrids utilising the Yaroslavl cattle breed.

   Modern research shows that innate immunity plays an important role in the pathogenesis of primary open-angle glaucoma (POAG). An increase in the content of toll-like receptors (TLR) in the glaucomatous retina of the human eye was revealed. TLRs can modulate the immune response in glaucoma; provide early recognition of damaging agents, activation of signaling pathways and effector mechanisms of the nonspecific immune defense system aimed at restoring homeostasis. The TLR-encoding genes’ polymorphism alters the amino acid structure of the receptors, which leads to changes in their immune functions: expression level, ligand-binding and coreceptor functions, transport and signal transmission.

   The aim was to analyze the association of the TLR2 (rs5743708), TLR3 (rs3775291), TLR4 (rs4986790, rs4986791) and TLR6 (rs5743810) polymorphisms with primary open-angle glaucoma in patients of Western Siberia.

   Methods: 99 patients (52 men and 47 women) with a diagnosis of primary open-angle glaucoma were examined. The comparison group consisted of 100 people (81 women and 19 men). TLR2 (rs5743708), TLR3 (rs3775291), TLR4 (rs4986790, rs4986791) and TLR6 (rs5743810) polymorphisms were analyzed by RT-PCR using test systems with Syber Green (Lytex, Russia). Statistical analysis was performed using the software package SPSS 23.0 and Arlequin 3.5.2.2.

   Results: the distribution of genotypes in the patient group and in the control group corresponded to the Hardy–Weinberg equilibrium. The genotype frequencies did not significantly differ between the two analyzed groups. The frequency of TLR2-753 ArgArg:TLR6-249 ProPro was increased in the group of patients with POAG. The linkage disequilibrium between two polymorphic positions of the TLR4 gene was revealed. In addition, the linkage disequilibrium between TLR2-TLR6 gene for the glaucoma group and the control group was revealed.

   Conclusion: an increase in certain genotypes in the patient group relative to the control group may indirectly indicate the involvement of infectious factors in the initiation of POAG. However, despite the proven importance of the participation of their protein products in the pathogenesis of glaucoma, the relationship of TLR polymorphism requires additional research taking into account the ethnic characteristics of patients and intergenic interactions for a better understanding of the complex mechanisms of disease development. This will help carry out early diagnosis and develop the necessary therapeutic strategy.

   Ischemic heart disease (IHD) is an important medical and social problem. ST-elevation myocardial infarction (STEMI) is the most severe form of IHD, affecting all layers of the heart muscle. One of the diagnostic criteria for endothelial dysfunction in myocardial infarction is the level of sE-selectin, a cell adhesion molecule that recruits neutrophils and induces neutrophil inflammation.

   The aim of this study is to investigate intronic polymorphisms rs5353, rs3917412 and rs1534904 of the E-selectin coding gene SELE in patients with STEMI. We have analyzed a group of patients with STEMI (n = 74) and a population sample of Tomsk (n = 136) as the control group.

   The frequencies of the rs5353 genotypes in the SELE gene have shown statistically significant differences between patients and the control sample (p = 0.004). The CC genotype is a predisposing factor to STEMI (OR = 6.93, CI:95 % (1.84–26.04), χ² = 8.69, p = 0.002). The analyzed mar kers were not studied previously in cardiovascular diseases (CVDs) and were rarely involved in association studies at all; there is no information on these SNPs in the leading databases. At the same time, all three variants, according to the RegulomeDB classification, belong to the functional class 1f, and are highly likely to have regulatory potential relative not only to the SELE gene, but also to other genes in the nearby region. The analysis of the functional significance of the studied markers has shown the presence of a region more extensive than one gene, which is co-regulated by the studied nucleotide substitutions. The association of rs5353 with STEMI identified in this study once again confirms the involvement of the SELE gene in the pathogenesis of CVDs. It is possible that this entire region of the genome may be involved indirectly in the pathogenesis of CVD through the systems of inflammation, immune response and DNA repair.

   Pathogenic variants in the SLC26A4 gene (OMIM #605646), leading to non-syndromic recessive hearing loss type 4 (DFNB4) and Pendred syndrome, significantly contribute to the etiology of hearing loss in many populations of the world. The spectrum and prevalence of different pathogenic SLC26A4 variants are characterized by wide ethno-geographical variability. A high frequency of some of them in certain regions of the world may indicate either their independent origin or be a consequence of the founder effect. The proportion of SLC26A4-associated hearing loss in Tuvinian patients (the Tyva Republic, Southern Siberia) is one of the highest in the world (28.2 %) and the vast majority of mutant SLC26A4 alleles are represented by three pathogenic variants c.919-2A>G, c.2027T>A and c.1545T>G (69.3, 17.5 and 8.0 %, respectively). Their overall carrier frequency in the Tuvinian population reaches 7.1 %. The accumulation of these variants in Tuvinian patients suggests a role of the founder effect in their prevalence in Tuva, which can be confirmed by the common genetic background (haplotypes) for each of them. For reconstruction of haplotypes in the carriers of variants c.1545T>G and c.2027T>A, the genotyping data of a panel of polymorphic genetic markers were used: five STRs (four of them flank the SLC26A4 gene at different distances and one is intragenic) and nine intragenic SNPs. Comparative analysis of the reconstructed haplotypes for c.1545T>G and c.2027T>A with previously obtained data on haplotypes for the c.919-2A>G variant showed that each of the analyzed variants has a specific (similar for all carriers of a particular variant) genetic background, apparently inherited from different “founder ancestors”. These data confirm the cumulative founder effect in the prevalence of pathogenic variants c.1545T>G, c.2027T>A, and c.919- 2A>G of the SLC26A4 gene in the indigenous population of the Tyva Republic. The obtained data are relevant both for predicting the prevalence of SLC26A4-caused hearing loss and for development of region-specific DNA diagnostics of inherited hearing loss in the Tyva Republic.

   The fundamental understanding of many biological processes that unfold in a human body has become possible due to experimental studies on animal models. The backbone of modern biomedical research is the use of mouse models for studying important pathophysiological mechanisms, assessing new therapeutic approaches and making decisions on acceptance or rejection of new candidate medicines in preclinical trials. The use of mice is advantageous because they have small size, are easy to keep and to genetically modify. Mice make up more than 90 % of the rodents used for pharmaceutical research. We present the pilot version of MiceDEGdb, a knowledge base on the genes that are differentially expressed in the mouse used as a model object in biomedical researc h. MiceDEGdb is a collection of published data on gene expression in mouse strains used for studying age-related diseases, such as hypertension, pe rio dontal disease, bone fragility, renal fibrosis, smooth muscle remodeling, heart failure and circadian rhythm disorder. The pilot release of MiceDEGdb contains 21,754 DEGs representing 9,769 unique Mus musculus genes the transcription levels whereof were found as being changed in 25 RNA-seq experiments involving eight tissues – gum, bone, kidney, right ventricle, aortic arch, hippocampus, skeletal muscle and uterus – in six genetic mouse strains (C57BL/6J, Ren1cCre|ZsGreen, B6.129S7(Cg)-Polgtm1Prol/J, BPN/3J, BPH/2J and Kunming) used as models of eight human diseases – all these data were based on information in 10 original articles. MiceDEGdb is novel in that it features a curated annotation of changes in the expression levels of mouse DEGs using independent biomedical publications about same-direction changes in the expression levels of human homologs in patients with one disease or the other. In its pilot release, MiceDEGdb documented 85,092 such annotations for 318 human genes in 895 diseases, as suggest to 912 scientific articles referenced by their PubMed ID. The information contained in MiceDEGdb may be of interest to geneticists, molecular biologists, bioinformatics scientists, clinicians, pharmacologists and genetic advisors in personalized medicine. MiceDEGdb is freely available at https://www.sysbio.ru/MiceDEGdb.

   Anxiety is a normotypic human condition, and like any other emotion has an adaptive value. But excessively high or low anxiety has negative consequences for adaptation, which primarily determines the importance of studying these two extreme conditions. At the same time, it is known that the perception of aversive stimuli associated with anxiety leads to changes in the activity of the brain’s cingulate cortex. The advantage of animals as models in studying the genetic bases of anxiety in humans is in the ability to subtly control the external conditions of formation of a certain state, the availability of brain tissues, and the ability to create and study transgenic models, including through the use of differentially expressed genes of small laboratory animals from the family Muridae with low and high anxiety. Within the framework of the translational approach, a three-domain potential gene network, which is associated with generalized anxiety in humans, was reconstructed using mouse models with different levels of anxiety by automatically analyzing the texts of scientific articles. One domain is associated with reduced anxiety in humans, the second with increased anxiety, and the third is a dispatcher who activates one of the two domains depending on the status of the organism (genetic, epigenetic, physiological). Stages of work: (I) A list of genes expressed in the cingulate cortex of the wild type CD-1 mouse line from the NCBI GEO database (experiment GSE29014). Using the tools of this database, differences in gene expression levels were revealed in groups of mice with low and high (relatively normal) anxiety. (II) Search for orthologs of DEG in humans and mice associated with anxiety in the OMA Orthology database. (III) Computer reconstruction using the ANDSystem cognitive system based on (a) human orthologous genes from stage (III), (b) human genes from the MalaCards database associated with human anxiety. The proven methods of the translational approach for the reconstruction of gene networks for behavior regulation can be used to identify molecular genetic markers of human personality traits, propensity to psychopathology.