Vavilovskii Zhurnal Genetiki i Selektsii最新文献

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.

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 ethnogeographical 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.

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.

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 markers 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.

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), Da, Dg, 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, Da, Dg, 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.

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.

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.

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.

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.

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.