Hearing loss caused by environmental or genetic factors concerns more than 10 % of the world population. It leads to disability and considerably reduces the life quality of deaf people. On average, 1 in 1,000 newborns are born deaf, and 50-60 % of cases are due to genetic causes. Nonsyndromic hereditary deafness is a monogenic disease with uniquely high genetic heterogeneity. The prevalence of some forms of genetic deafness varies in different populations and could be determined, as for many other genetic diseases, by the ethnic composition of a population, isolation, founder and «bottleneck» effects, the proportion of consanguineous marriages, and probable heterozygote advantage. It is assumed that high prevalence of hearing loss due to mutations in the GJB2 (Cx26) gene was also influenced by some social factors: a long-standing tradition of assortative marriages between deaf people, combined with growth of their social adaptation and genetic fitness. The start for these events was the breakdown of the deep social isolation of deaf people, which occurred about 300 years ago in Europe, and later in the US, when special schools for the deaf with learning sign language as a common tool for communication were established (linguistic homogamy). Computer simulations and comparative retrospective study showed that over the past 200 years these social processes can have doubled the frequency of deafness in the US caused by the GJB2 gene mutations. Information about the sociodemographic structure of deaf communities in the past is extremely limited by an almost complete lack of relevant archival data. Nevertheless, studies of sociodemographic and medical-genetic characteristics of deaf people’s contemporary communities are important for predicting the prevalence of inherited forms of deafness, as well as for understanding the impact of social factors on the evolutionary processes occurring in human populations.

The work concerns a polymorphism of the cytochrome Р450 CYP1A1 gene, the CYP1A1*2C variant (Ile462Val, rs1048943). This substitution results in a two- fold increase in enzyme activity, which leads to accumulation of active intermediates and increases the risk of DNA mutations and chemically induced carcinogenesis. It has been demonstrated that the 462Val allele may be a risk factor in some oncological and other multifactorial diseases. This study was performed on Tundra Nenets in Yamalo-Nenets Autonomous Okrug (N = 271), Nganasans in the Taimyr Peninsula (N = 186) and Russians in North Siberia (N = 267). The cohorts did not include descendants of mixed marriages. Genotyping was performed using Real-Time PCR with competitive TaqMan allele-specific probes. The frequency of the 462Val allele in the Tundra Nenets cohort was 23.8 % (95 % CI 20.4–27.6 %), which corresponds to the frequency range found in East Asian populations and is higher than the values typical of European populations. The 462Val allele frequency in the Russian cohort was 5.8 % (95 % CI 4.1–8.1 %), which corresponds to the frequency range of European populations. The 462Val allele frequency in the Nganasans cohort was 39.0 % (95 % CI 34.2–44.0 %), which is higher than the frequencies found in European, Asian and African populations. Frequencies of the  462Val variant close to that in Nganasans have been observed in Greenland Inuits, native Americans as a whole and the Southern Chinese. A high-frequency occurrence of the 462Val allele among Tundra Nenets and Nganasans may be indicative of a populationwide risk of diseases influenced by this genetic polymorphism, especially when traditional mainstays are gone or previously unknown ecotoxicants appear in the areas.

A large number of studies showed that the gene EPAS1 may serve as a possible predictor of success in sports because of its influence on the processes of oxygen transportation and consumption. However, data concerning the impact of EPAS1 polymorphisms on sports achievements in the modern research literature are very scarce and contradictory. The aim of the present paper was to study genetic selection in the polymorphic system of the EPAS1 gene (rs1867785) in a group of male sambo practitioners. 312 Russian males from 18 to 30 years of age were studied. Of them, 220 were professional athletes and 92 were non-athletes, who served as the control group. The genotype of a single nucleotide G/A polymorphic system of the EPAS1 gene was determined for each participant of the study. Analysis of genotype frequencies revealed statistically significant differences between the two groups. An increase of АА and AG genotype frequencies was revealed in the group of athletes (χ2 = 8.68, p = 0.01). Thus, for sambo practitioners, who reached high levels, the presence of the minor А-allele in the genotypes was typical. The odd ratio (OR) calculated for this group was 1.800 (95 % CI 1.227–2.641), demonstrating that the carriers of the А-allele of the EPAS1 gene had some advantages over the carriers of the G-allele. OR for the highest-rank wrestlers was even higher, 1.990 (95 % CI 1.195–3.313). These results suggest directed genetic selection in the А-allele carriers of the EPAS1 gene among sambo practitioners.

The article presents data on destabilization signs in response to selection for catatonia at an organismal level. Experiments were conducted with the unique GC (genetic catatonia) rat strain selected for long passive-defensive freezing. The goal of this study was to detect destabilization signs in the behavioral and somatovegetative parameters of GC rats emerging in response to selection. The destabilization manifested itself as changes in rat attitudes towards humans, as became apparent from the glove test. Altered hormone levels in GC rats were detected: corticosterone concentrations were reduced in feces and increased during handling. The metabolic system showed a decrease in energy stored accompanying the fast (glucose level) and slow (triglyceride level) responses. However, the strains did not differ in the concentration of insulin, which affects glucose transport through the cell membrane. Nor did we find differences between Wistar and GC rats in cholesterol level. This lipid is important for both energy and constructive metabolism. A side effect of selection for catatonia was the worse pelage status in GC rats. The overall physical condition of catatonic rats involved reduced body weight in both neonates and adults. All these changes point to the modification of behavioral and somatovegetative patterns and intensification of the passive-defensive component of selection in GC rats.

One of the most important areas of research in the biology and genetics of farmed animals is one of identification of genes controlling the expression of traits with practical importance for animal breeding. For most of these characteristic features, wide variation in gene expression in specific loci, which are called quantitative trait loci (QTL), is typical. Eggs have been researched for decades due to their importance for the reproduction of birds, as well as for its widespread use in pharmaceutical, cosmetic and food industries. Breeding hens and cross-lines is a necessary step for producing eggs with desired quality. The results of this work are recommended for use to create systems of molecular markers for marker selection of layers and obtain new lines and cross hens with larger mass eggs. Compared to existing conventional systems of selecting layers on this basis, this will eliminate the assessment of the genotype of male progeny, which will significantly reduce breeding time. The system of markers will appear as a set of primers for detection of gene alleles that have a significant impact on the characteristics as above. The use of the molecular markers of high-performance systems for direct selection on the basis of domestic chicken eggs would lead to substantial progress in biotechnology poultry and help avoid having to purchase similar systems from outside the country. The association of the condensin NCAPG gene with the egg traits of domestic chicken has been studied. Associations of the SNP alleles of the rs14491030 marker localized in exon 8 of the NCAPG gene with the trait “the weight eggs”, p < 0.001, as well as with the elastic deformation of the egg shell, p < 0.026, have been found. It has been found that a single nucleotide nonsynonymous A G substitution leads to a significant increase in egg weight. The marker SNP rs14491030 with the observed significant effect on the trait «egg weight» can be recommended for use in breeding of laying hens. Calculations of the relative fitness of genotypes of the marker SNP rs14491030  suggest natural selection for heterozygotes. The results obtained are discussed in connection with the role of the canonical condensin complex in the compaction of chromatin and segregation of chromosomes.

The search for single nucleotide polymorphisms (SNP) in the myostatin gene is a promising direction of research as this gene is involved in the development of important biological and productive traits in chicken. Using PCR-RFLP technique, an analysis of allele and genotype frequencies in Cornish chicken breed of G5 line of Smena-8 cross has been conducted. Two pairs of primers allowing PCR product to be obtained in the myostatin gene have been used. Two single nucleotide substitutions on exon 1 of the myostatin gene have been under investigation: G/A in MST2109 and G/С in MST2244. A signifiant predominance of deoxynucleotide G in MST2244 over C and deoxynucleotide A over G in MST2109 has been observed. Differences in productive traits between genotypes in MST2109 were not detected. Analysis of allelic variability by MST2244 locus showed statistically significant differences in live weight at the age of 7 days between CC and G2G2 genotypes (p < 0.01), CG2 and G2G2 (p < 0.05). G2G2 individuals (203.52 g) were significantly heavier than CC (179.5 g) and CG2 (193.95 g) chickens at the age of 7 days. Statistically significant differences between the CC and G2G2 genotypes in live weight at the age of 33 days have been revealed (p < 0.05). Thus, this research has led to a better understanding of allele frequencies in the myostatin gene in line G5 of Cornish breed. The results obtained will allow particular myostatin gene-based genotypes to be taken into account for accelerating the breeding process in the broiler poultry industry.

We used molecular-genetic and molecular-cytology approaches to characterize the genomes of 20 varieties of wheat created in different regions of Russia. A molecular-genetic analysis was performed using 29 SSR-markers covering the entire genome, and 41 ISBP-markers localized on chromosome 5B. Analysis of genetic similarity based on the results of molecular genotyping showed that the winter wheat varieties form a common cluster, regardless of the origin or area of cultivation. This is primarily due to the fact that the varieties originating from the European part of Russia were used to establish winter wheat varieties for West Siberia. Comparative analysis of individual dendrograms constructed using 1–2 markers per chromosome, and with the involvement of a larger number of 5B-chromosome markers allowed us to identify varieties with rearrangements of this chromosome and to assess genetic diversity. We found that winter wheat Vassa and spring wheat Chelyaba 75 were clustered closely together. This is an indirect confirmation of the use of winter wheat varieties in the breeding to improve the productive potential of spring wheat. Molecular-cytology analysis by C-banding and fluorescence in situ hybridization (FISH) revealed various chromosomal rearrangements in 8 of 20 cultivars studied, including translocations from S. cereale, Ae. speltoides and Th. intermedium. Thus, a combination of the two approaches allowed us to better characterize genomes of wheat varieties of various origin.

Brassica oleraceae var. capitata L. is characterized by a high level of intraspecific heterogeneity due to some biological features that cause difficulties for breeding creating genetically homogenous forms and maintaining their genetic purity. Microsatellites (SSR) are highly polymorphic markers of plant genomes and represent one of the most effective tools for assessing genetic polymorphism. Among microsatellites, EST-SSR are most interesting, because they are directly linked to the expressed sequences and for that reason are widely used for analysis of genetic diversity and population structure. In this work, we studied the effectiveness of the use of transferable EST-SSR markers for both analyzing white cabbage diversity and genotyping pure lines. As a result, 15 microsatellite loci were characterized for the information content, allelic frequencies and heterogeneity levels. The effective multiallelic markers (Bo20TR, BoDCTD4, BoPC34, BoPLD1, BoCalc, BoPC15) with high information content (PIC > 0.7) that could be successfully used for analysis of inter- and intravarietal polymorphism in B. oleracea var. capitata were identified. It has been shown that intervarietal polymorphism expressed as the allelic diversity of EST SSR loci greatly facilitates varietal identification and typing of individual plants for breeding purposes. Based on the SSR-evaluation and subsequent clustering, the genetic structure of the breeding collection was identified, which showed that most experimental forms, in spite of different origin, have a common ancestral genetic basis. The identified donors of rare alleles could potentially be a source of valuable genetic segregation for further B. oleracea breeding improvement.

Spike parameters of hexaploid wheats from the genus Triticum L. are determined by the major genes and play an important role in systematics. Having a strong pleiotropic effect they are also have a practical importance. In this work, the interaction of the dominant genes QS and Q with the dominant gene C17648 determining a spike shape was investigated. The gene Q is situated in 5AL chromosome and determines the formation of elongated lax spike in the species T. spelta L. The homoeoallelic gene QS introgressed into bread wheat from Aegilops speltoides Tausch. and causing the formation of speltoid spike also situated in 5AL chromosome of the line 84/98w. The gene C17648 is analogous in the phenotypic manifestation to the gene C determining the formation of a dense short spike on a short culm like in T. compactum Host. It was mapped to 5AL chromosome in bread wheat line ANBW-5A and the donor of the gene was a mutant of durum wheat. In the present work, spike length, spikelet number, index of spike density and stem length were studied in F1 , F2 and F3 of three different hybrid populations. For the first time it was showed that the gene C17648 is epistatic to the dominant genes QS and Q. It was manifested in the formation of compact spike in F1 hybrids and in numerical prevalence of plants with a compact spike in F2 . At the same time, the gene C17648 showed a smaller effect on stem length and did not affected spikelet number. Using the genetic analysis it was found that the genes QS and Q are independently inherited from the gene C17648 but a substantial linkage was observed between QS or Q and b1 gene.

Drosophila Pnut protein belongs to the family of septins, conservative GTPases participating in cytokinesis and many more other fundamental cellular processes. Because of their filamentous appearance, membrane association and functions, septins are considered as the fourth component of the cytoskeleton, along with actin, microtubules and intermediate filaments. However, septins are much less studied than the other cytoskeleton elements. We had previously demonstrated that deletion of the peanut (pnut) gene leads to mitotic abnormalities in somatic cells. The goal of this work was to study the role of pnut in Drosophila spermatogenesis. We designed a construct for pnut RNA interference allowing pnut expression to be suppressed ectopically. We analyzed the effect of pnut RNA interference on Drosophila spermatogenesis. The most sensitive to Pnut depletion were germ line cells at the earliest stages of spermatogenesis: the suppression of pnut expression at these stages leads to male sterility as a result of immotile sperm. Testes of those sterile males did not show any significant meiotic defects; axonemes and mitochondria were normal. We also analyzed the effect of mutations in Pnut conservative domains on Drosophila spermatogenesis. Mutations in the GTPase domain resulted in cyst elongation defects. Deletions of the C-terminal domain led to abnormal testis morphology. Both GTPase domain and C-terminal domain mutant males were sterile and produced immotile sperm. To summarize, we showed that Pnut participates in spermiogenesis, that is, late stages of spermatogenesis, when major morphological changes in spermatocytes occur.

The main method of pest control is by applying chemical insecticides. The efficacy of insecticides is reduced due to the development of resistance by pest populations. This is an especially important problem with the Colorado potato beetle. There are different strategies for the use of insecticides to slow the development of resistance. Based on long lasing research, we propose a hypothesis about delaying the development of resistance by applying insecticides at low doses. To test this hypothesis, we have built predictive discrete genetic models of resistance in Colorado potato beetle populations. The model based on the classical equations of population genetics has been supplemented by various factors. Calculations of the survival rates of Colorado potato beetle individuals were carried out taking into account the statistical regularities of the distribution of the toxic substance after treatment by insecticides. We have calculated the survival rates of different genotypes using a lognormal distribution after changing the insecticide dose two-fold or more. The factor of differentiated mortality during the winter was additionally introduced into the model. The use of phenetic markers of nonspecific resistance to environmental factors allowed us to compute the model with mediated intergenic interactions. Various hypotheses about strategies in overcoming resistance have been tested using this model. Calculations demonstrated that the use of insecticides at minimum effective doses (low dose) leads to a slower increase in the proportion of resistant individuals in populations of the Colorado potato beetle for two seasons. Resistance develops much more slowly following alternate treatment with insecticides from different chemical classes. The best strategy is through off-season treatment with insecticides of different chemical classes at lower doses. 

A somatic mutation and recombination test (SMART) on the wing cells of Drosophila melanogaster is described in this article in detail. SMART can be used to evaluate the effect of various factors on the genome: physical (temperature, various types of radiation, electromagnetic fields), biogenic (genetic, physiological, infectious factors) and a wide range of chemical compounds. SMART is used as an in vivo version of the method for evaluating promutagenic and mutagenic properties of food, food supplements, potential drugs and cosmetics, and environmental pollutants. The method is based on the influence of the agents under study on the dividing cells of the wing imaginal discs of larvae heterozygous for recessive mutations, marking the wing cells. The mutations, multi wing hairs (mwh; 3 – 0.3) and flare (flr; 3 – 38.8), are located on the left arm of chromosome 3. The Drosophila melanogaster wing contains 24,400 cells arranged in two layers. Each normal cell has only one wing fiber. Recombination or mutational events in the cell leads to the formation of mutant spots/clones visible by microscopic analysis of the wing surface. The Drosophila and mammalian detoxication system is arranged on similar principles, which are based on the action of cytochrome P450. There are modifications to SMART, based on elevated cytochrome P450 expression, allowing more reliable extrapolation of the test results to mammals. Detailed recommendations for the use of the SMART method on the wing cells of Drosophila melanogaster presented in the paper can be used as a textbook in practice and for training purposes.

Histones, the major protein components of chromatin, undergo post-translational modifications, which particularly affect the structural and functional organization of chromosomes. The most common post-translational modifications are phosphorylation, methylation, acetylation and ubiquitination. Histone phosphorylation occurs mainly at N-terminal tails of serines (Ser) and threonines (Thr), and coordinates various processes of mitotic and meiotic division. It has been shown that this type of modification is required for activation of transcription, DNA damage repair, recombination and also for chromosome condensation and segregation. Histone H3 is characterised by the presence of a large number of modification sites among the four core histones. In plants, phosphorylation of histone H3 at serine positions 10 and 28 and at threonine positions 3, 11, 32 and 133 is the most well studied. This review contains the most complete data on the spatial and temporal distribution of H3 phosphorylation of serine at position 10 (phH3Ser10) in mitosis and meiosis in different plant species. Most species are characterised by phosphorylation of the centromeric region in mitosis and second meiotic division, and by phosphorylation throughout the chromosomes in the first meiotic division. However, there are exceptions to the phH3Ser10 distribution in mosses and cestrum, as well as in species with holocentric chromosomes. There are contradictory data on the phH3Ser10 distribution in mitosis and meiosis in the same species. The functional significance of phH3Ser10 in cell division in plants is associated with the activity of the centromere, centromere cohesion and sister chromatid and chromosome segregation. We discuss the participation of currently known candidate kinases and phosphatases in the dynamics of H3Ser10 phosphorylation. The review provides an overview of the role of phH3Ser10 modification in the chromosome division and segregation in mitosis and meiosis.

Existence of a small subset of cancer cells referred to as tumor initiating stem cells (TISCs) largely responsible for tumor progression and resistance to chemotherapeutic cytostatic drugs reperesent an important recent paradigm shift. The present work is the first report in the series of papers from our group where we describe the development of anticancer therapy based on the selective targeting of TISCs. Here were characterize a cytoreductive activity of cyclophosphamide (CP), double-stranded DNA (dsDNA) and combinations thereof against the TISC population present in mouse Krebs-2 ascites. We evaluated engraftment potential of Krebs-2 cancer cells treated in ascites-bearing mice in vivo, followed by re-engraftment to congenic recipient mice in a form of a solid graft. These data indicate that with our approach TISCs can be completely eliminated even from a well-established ascites. We demonstrate that dsDNA-internalizing and CD34-positive cells are more sensitive to the synergistic effects of CP and dsDNA. When Krebs-2 ascites are treated with human DNA 1-12 hours post CP injection, this results in either elimination of cells that internalize TAMRA-labeled DNA (TISCs) or alters their phenotype, which is accompanied with the loss of surface expression of CD34. Next, we show that the timepoint 18 hrs post CP treatment is critical to the ongoing repair process in that it divides the repair into two phases: nucleotide excision repair + dsDNA break repair and homologous recombination. Importantly, both of these phases can be conveniently used for targeting the tumorigenic potential of the graft. In the context of monotherapy, CP is most effective against ascites grafts when administered as serial injections. To achieve maximum efficiency, the timing of consecutive injections must match the time when cancer cells found at G2/M during the first injection enter G1/S and/or the time of active repair via homologous recombination.

In the present paper, we report on the series of experiments where multiple regimens of CP and dsDNA injections were tested for targeting the ascites form of murine Krebs-2 cancer in situ. We show that combining CP with cross-linked human and salmon dsDNA results in a synergistic toxicity for ascites-bearing mice, an observation supported by the histopathology analysis of organs and tissues of experimental animals. In contrast, using a composite mixture of native and cross-linked human and salmon DNA after CP injections leads to a significant increase in average lifespan of the treated mice. Further, we demonstrate that repeated rounds of CP+dsDNA injections result in dramatic anticancer effect. The timing of injections is chosen so that they target the cells that were insensitive to the previous treatments as they were in the G2/M phase. 3-4 rounds of injections are needed to eliminate the subpopulation of tumor-initiating cancer stem cells. Our experiments identified the regimen when complete resorption of the primary Krebs-2 ascites occurs in all of the treated animals, followed by a remarkable remission period lasting 7-9 days. Yet, this regimen does not prevent secondary site metastases (either solid or ascites form) from developing, which is likely caused by the migration of ascites cells into adjacent tissues or by incomplete eradication of cancer stem cells. To address these and other questions, we expanded the study and performed histopathology analysis, which indicated that secondary metastases is not the only cause of death. In fact, many animals displayed unfolding systemic inflammatory reaction which was culminated by multiple organ failure. Thus, we developed the concept for treating ascites form of Krebs-2 cancer, which allows elimination of the primary ascites.

Earthworms are a widespread and ecologically important group of animals, which has the highest total biomass in some ecosystems and often defines the composition of soil fauna. Earthworms are known to have high cryptic genetic diversity. In this study we attempted to estimate earthworm species diversity in the south of West Siberia by DNA barcoding. This method employs short fragments of the genome to identify species, and allows one to work with specimens that cannot be identified by conventional techniques, as well as to search for new species and predict their phylogenetic affinities. As the target sequence we took a fragment of the mitochondrial cytochrome oxidase 1 (cox1) gene. The studied territory (Novosibirsk and Tomsk oblasts, Altai krai, and the Altai Republic) is known to contain 16 species and subspecies of earthworms. We analyzed 259 individuals from twelve locations and detected 27 genetic clusters. Ten of them correspond to known species (A. caliginosa, E. fetida, O. tyrtaeum, D. r. tenuis, D. octaedra, E. balatonica, E. sibirica, as well as three genetic lineages of E. nordenskioldi nordenskioldi). Seventeen of the 27 clusters do not have close sequence similarity to any known earthworm species. Representatives of some of these novel clusters are morphologically similar to the Eisenia n. nordenskioldi/E. n. pallida species complex and may belong to new genetic lineages of this complex. The rest of the novel clusters probably represent new earthworm species. Therefore, we can conclude that a large portion of earthworm biodiversity in the south of West Siberia is still unexplored.