The SMC protein family, including cohesin and condensin I/II, plays a pivotal role in maintaining the topological structure of chromosomes and influences many cellular processes, notably the repair of double-stranded DNA breaks (DSBs). The cohesin complex impacts DSB repair by spreading γH2AX signal and containing DNA ends in close proximity by loop extrusion. Cohesin supports DNA stability by sister chromatid cohesion during the S/G2 phase, which limits DNA end mobility. Cohesin knockdown was recently shown to stimulate frequencies of genomic deletions produced by distant paired DSBs, but does not affect DNA repair of a single or close DSBs. We examined how auxin-inducible protein degradation of Rad21 (cohesin) or Smc2 (condensins I+II) changes the frequencies of rearrangements between paired distant DSBs in mouse embryonic stem cells (mESCs). We used Cas9 RNP nucleofection to generate deletions and inversions with high efficiency without additional selection. We determined optimal Neon settings and deletion appearance timings. Two strategies for auxin addition were tested (4 independent experiments in total). We examined deletion/inversion frequencies for two regions spanning 3.5 and 3.9 kbp in size. Contrary to expectations, in our setting, Rad21 depletion did not increase deletion/inversion frequencies, not even for the region with an active Ctcf boundary. We actually observed a 12 % decrease in deletions (but not inversions). At the same time, double condensin depletion (Smc2 degron line) demonstrated high biological variability between experiments, complicating the analysis, and requires additional examination in the future. TIDE analysis revealed that editing frequency was consistent (30–50 %) for most experiments with a minor decrease after auxin addition. In the end, we discuss the Neon/ddPCR method for deletion generation and detection in mESCs.

Metapolycentromeres consist of multiple sequential domains of centromeric chromatin associated with a centromere-specific variant of histone H3 (CENP-A), functioning collectively as a single centromere. To date, they have been revealed in nine flowering plant, five insect and six vertebrate species. In this paper, we focus on their structure and possible mechanisms of emergence and evolution. The metapolycentromeres may vary in the number of centromeric domains and in their genetic content and epigenetic modifications. However, these variations do not seem to affect their function. The emergence of metapolycentromeres has been attributed to multiple Robertsonian translocations and segmental duplications. Conditions of genomic instability, such as interspecific hybridization and malignant neoplasms, are suggested as triggers for the de novo emergence of metapolycentromeres. Addressing the “centromere paradox” – the rapid evolution of centromeric DNA and proteins despite their conserved cellular function – we explore the centromere drive hypothesis as a plausible explanation for the dynamic evolution of centromeres in general, and in particular the emergence of metapolycentromeres and holocentromeres. Apparently, metapolycentromeres are more common across different species than it was believed until recently. Indeed, a systematic review of the available cytogenetic publications allowed us to identify 27 candidate species with metapolycentromeres. Тhe list of the already established and newly revealed candidate species thus spans 27 species of flowering plants and eight species of gymnosperm plants, five species of insects, and seven species of vertebrates. This indicates an erratic phylogenetic distribution of the species with metapolycentromeres and may suggest an independent emergence of the metapolycentromeres in the course of evolution. However, the current catalog of species with identified and likely metapolycentromeres remains too short to draw reliable conclusions about their evolution, particularly in the absence of knowledge about related species without metapolycentromeres for comparative analysis. More studies are necessary to shed light on the mechanisms of metapolycentromere formation and evolution. 

Blue-grain lines were created on the basis of the spring bread wheat variety Saratovskaya 29 (S29) with chromosome 4B or 4D replaced with chromosome 4Th from Thinopyrum ponticum. The leaf pubescence of the two lines differs from S29 and from each other. In this work, we studied the effect of these substitutions on the manifestation of this trait. To quantify pubescence, the LHDetect2 program was used to determine trichome length and number on the leaf fold microphotographs. The key gene Hl1 on chromosome 4B and another unidentified gene with a weak effect determine the leaf pubescence of the recipient S29. Their interaction leads to the formation of trichomes of up to 300 microns in length. Replacement of both copies of chromosome 4B with two copies of wheatgrass chromosome 4Th modifies leaf pubescence in line S29_4Th(4B) so that the leaf pubescence characteristic of S29 becomes more sparse, and trichomes of up to 600–700  µm in length are formed. Additionally, we described modification of pubescence in the substitution line S29_4Th(4D) where chromosome 4D that does not carry any pubescence gene was replaced. Under this substitution, trichomes of up to 400 µm in length were formed and the average length of trichomes on the underside of the leaf was reduced. The replacement of the Hl1 gene in the lines was also confirmed by the allelic state of the linked microsatellite marker Xgwm538. Thus, as a result of the studies, a new leaf pubescence gene introgressed from Th. ponticum into bread wheat was identified. We designated it as Hl1th. For the purpose of selection, we propose to use the unlicensed informative microsatellite markers Xgwm538 and Xgwm165, allowing chromosomes 4A, 4B, 4D and 4Th to be distinguished. 

The effect of T. aestivum L. chromosomes 1A and 1D on fertility of recombinant bread wheat allolines of the same origin carrying the cytoplasm of barley H. vulgare L. and different levels of cytonuclear compatibility was studied. Alloline L-56 included mainly fully sterile (FS) and partially sterile (PS) plants, alloline L-57 included partially fertile (PF) plants and line L-58 included fertile (F) ones. Analysis of morphobiological traits and pollen painting indicated complete or partial male sterility in plants of allolines L-56 and L-57. To differentiate genotypes with cytonuclear coadaptation and genotypes with cytonuclear incompatibility, PCR analysis of the 18S/5S mitochondrial (mt) repeat was performed. Heteroplasmy (simultaneous presence of barley and wheat mtDNA copies) was found in FS, PS, PF and some F plants, which was associated with a violation of cytonuclear compatibility. Wheattype homoplasmy (hm) was detected in the majority of the fertile plants, which was associated with cytonuclear coadaptation. The allolines used as maternal genotypes were crossed with wheat-rye substitution lines 1R(1A) and 1R(1D). In F1, all plants of PF×1R(1A) and PF×1R(1D) combinations were fertile, and in F2, a segregation close to 3 (fertile) : 1 (sterile) was observed. These results showed for the first time that chromosomes 1A and 1D carry one dominant Rf gene, which controls the restoration of male fertility of bread wheat carrying the cytoplasm of H. vulgare. All plants of F1 combinations FS×1R(1A), FS×1R(1D), PS×1R(1A), PS×1R(1D) were sterile, which indicates that a single dose of genes localized on wheat chromosomes 1A or 1D is not enough to restore male fertility in FS and PS plants. All plants of hybrid combinations F(hm)×1R(1A) and F(hm)×1R(1D) in both F1 and F2 were fertile, that is, fertility of allolines with cytonuclear coadaptation does not depend on wheat chromosomes 1A and 1D. 

Eggplant (Solanum melongena L.) ranks fifth in importance among vegetable crops of the Solanaceae family, in part due to the high antioxidant properties and polyphenol content of the fruit. Along with the popular purplefruited varieties of S. melongena, there are cultivars, the fruits of which are rich in phenolic compounds, but are whitecolored due to the lack of anthocyanin biosynthesis. Determination of the amount of anthocyanins and other phenolic compounds, as well as carotenoids and sugars, is included in the assessment of the quality of eggplant fruits of commercial (technical) ripeness. In addition to antioxidant and taste properties, these metabolites are associated with fruit resistance to various stress factors. In this study, a comparative analysis of the content of anthocyanins, carotenoids and soluble sugars (sucrose, glucose, fructose) in the peel and pulp of the fruit of both technical and biological ripeness was carried out in purple-fruited (cv. Vlas) and white-fruited (cv. Snezhny) eggplant accessions of domestic selection. The peel and pulp of biologically ripe fruits of the cvs Vlas and Snezhny were used for comparative transcriptomic analysis. The key genes of the flavonoid and carotenoid metabolism, sucrose hydrolysis, and soluble sugar transport were shown to be differentially expressed between fruit tissues, both within each cultivar and between them. It has been confirmed that the purple color of the peel of the cv. Vlas fruit is due to substantial amounts of anthocyanins. Flavonoid biosynthesis genes showed a significantly lower expression level in the ripe fruit of the cv. Vlas in comparison with the cv. Snezhny. However, in both cultivars, transcripts of anthocyanin biosynthesis genes (DFR, ANS, UFGT) were not detected. Additionally, the purple fruit of the cv. Vlas accumulated more carotenoids and sucrose and less glucose and fructose than the white fruit of the cv. Snezhny. Biochemical data corresponded to the differential expression pattern of the key genes encoding the structural proteins of metabolism and transport of the compounds analyzed. 

Imputation is a method that supplies missing information about genetic variants that could not be directly genotyped with DNA microarrays or low-coverage sequencing. Imputation plays a critical role in genome-wide association studies (GWAS). It leads to a significant increase in the number of studied variants, which improves the resolution of the method and enhances the comparability of data obtained in different cohorts and/or by using different technologies, which is important for conducting meta-analyses. When performing imputation, genotype information from the study sample, in which only part of the genetic variants are known, is complemented using the standard (reference) sample, which has more complete genotype data (most often the results of whole-genome sequencing). Imputation has become an integral part of human genomic research due to the benefits it provides and the increasing availability of imputation tools and reference sample data. This review focuses on imputation in human genomic research. The first section of the review provides a description of technologies for obtaining information about human genotypes and characteristics of these types of data. The second section describes the imputation methodology, lists the stages of its implementation and the corresponding programs, provides a description of the most popular reference panels and methods for assessing the quality of imputation. The review concludes with examples of the use of imputation in genomic studies of samples from Russia. This review shows the importance of imputation, provides information on how to carry it out, and systematizes the results of its application using Russian samples. 

The diversity of geographically distributed human populations shows considerable variation in external and internal traits of individuals. Such differences are largely attributed to genetic adaptation to various environmental influences, which include changes in climatic conditions, variations in sleep and wakefulness, dietary variations, and others. Whole-genome data from individuals of different populations make it possible to determine the specific genetic sites responsible for adaptations and to further understand the genetic structure underlying human adaptive characteristics. In this article, we searched for signals of single nucleotide polymorphisms (SNPs) under selection pressure in people of different populations. To identify selection signals in different population groups, the PER1, PER2 and PER3 genes that are involved in the coordination of thermogenic functions and regulation of circadian rhythms, which is directly reflected in the adaptive abilities of the organism, were investigated. Data were analyzed using publicly available data from the 1000 Genomes Project for 23 populations. The Extended Haplotype Homozygosity Score statistical method was chosen to search for traces of selection. The comparative analysis performed identified points subject to selection pressure. The SNPs were annotated through the GWAS catalog and manually by analyzing Internet resources. This study suggests that living conditions, climate, and other external factors directly influence the genetic structure of populations and vary across races and geographic locations. In addition, many of the selection variants in the PER1, PER2, PER3 genes appear to regulate biological processes that are associated with major modern diseases, including obesity, cancer, metabolic syndrome, bipolar personality disorder, depression, rheumatoid arthritis, diabetes mellitus, lupus erythematosus, stroke and Alzheimer’s disease, making them extremely interesting targets for further research aimed at identifying the genetic causes of human disease. 

The ability to metabolize lactose in adulthood is associated with the persistence of lactase enzyme activity. In European populations, lactase persistence is determined mainly by the presence of the rs4988235-T variant in the MCM6 gene, which increases the expression of the LCT gene, encoding lactase. The highest rates of lactase persistence are characteristic of Europeans, and the lowest rates are found in East Asian populations. Analysis of published data on the distribution of the hypolactasia-associated variant rs4988235-C in the populations of Central Asia and Siberia showed that the frequency of this variant increases in the northeastern direction. The frequency of this allele is 87 % in Central Asia, 90.6 % in Southern Siberia, and 92.9 % in Northeastern Siberia. Consequently, the ability of the population to metabolize lactose decreases in the same geographical direction. The analysis of paleogenomic data has shown that the higher frequency of the rs4988235-T allele in populations of Central Asia and Southern Siberia is associated with the eastward spread of ancient populations of the Eastern European steppes, starting from the Bronze Age. The results of polymorphism analysis of exons and adjacent introns of the MCM6 and LCT genes in indigenous populations of Siberia indicate the possibility that polymorphic variants may potentially be related to lactose metabolism exist in East Asian populations. In East Asian populations, including Siberian ethnic groups, a ~26.5 thousand nucleotide pairs long region of the MCM6 gene, including a combination of the rs4988285-A, rs2070069-G, rs3087353-T, and rs2070068-A alleles, was found. The rs4988285 and rs2070069 loci are located in the enhancer region that regulates the activity of the LCT gene. Analysis of paleogenomic sequences showed that the genomes of Denisovans and Neanderthals are characterized by the above combination of alleles of the MCM6 gene. Thus, the haplotype discovered appears to be archaic. It could have been inherited from a common ancestor of modern humans, Neanderthals, and Denisovans, or it could have been acquired by hybridization with Denisovans or Neanderthals. The data obtained indicate a possible functional significance of archaic variants of the MCM6 gene. 

The Nivkhs are a small ethnic group indigenous of the Russian Far East, living in the Khabarovsk Territory and on Sakhalin Island, descending from the ancient inhabitants of these territories. In the Nivkhs, a specific Sakhalin-Amur anthropological type is prevalent. They are quite isolated, due to long isolation from contacts with other peoples. The gene pool of the Nivkhs and other Far Eastern and Siberian populations was characterized using a genome-wide panel of autosomal single-nucleotide polymorphic markers and Y chromosome haplogroups. Bioinformatic processing of frequencies of autosomal SNPs, Y chromosome haplogroups and YSTR haplotypes showed that the Nivkh gene pool is very different from the other populations’. Analysis of the SNP frequencies using the PCA method divided the Far Eastern populations in full accordance with the territories of their residence into the northern group of the Chukchi and Koryaks and the southern group, including the Nivkhs and Udege. The remoteness of the Nivkhs coincides with their geographic localization, with the Nivkhs and Udege demonstrating the greatest kinship. The Nivkhs have a specific component of their gene pool, which is present with much less frequency in the Udege and Transbaikal Evenks. According to the IBD blocks, the genotypes of the Nivkhs show a very small percentage of coincidence with the Udege, Koryaks, Evenks and Chukchi, the value of which is the lowest compared to the IBD blocks among all other Siberian populations. The Nivkh-specific composition of haplogroups and YSTR haplotypes was shown. In the Nivkhs, the C2a1 haplogroup is divided into three sublines, which have a fairly ancient origin and are associated with the ancestors of modern northern Mongoloids. The Nivkh haplogroup O2a1b1a2a-F238 is found among residents of China and Myanmar. The Q1a1a1-M120 line is represented among the Nivkhs, Koryaks, Evenks and Yukaghirs. Phylogenetic analysis of individual Y chromosomal haplogroups demonstrated the closeness of the Nivkh gene pool with the ancient population of the Amur and Okhotsk regions, the Koryaks, the Tungus peoples and the population of Southeast Asia. The Nivkh gene pool confirms the relative smallness of their ancestral groups without mixing with other populations. 

Problematic video games use, as a specific form of problematic Internet use, is widespread among adolescents and can have negative effects on their mental and somatic well-being. An increasing incidence of addictive video gaming, as well as the overuse of the Internet, among the young population makes the current study of susceptibility factors, including the genetic component, relevant. There has been a number of investigations related to the involvement of gene variants of the neurotransmitter system in the development of Internet addiction, with the results being different for various ethnic groups. The dopamine type 2 receptor gene (DRD2) is one of the candidate genes for susceptibility to video game addiction. The aim of the work was to study polymorphic variants of the dopamine receptor gene DRD2 (rs6277, rs1800497) in Russian adolescents with problematic use of computer video games. A sampling of 407 adolescents aged 14.1±1.8 years was tested, of which 56 (13.8 %) were identified as having problems with the pathological use of video games use based on the GASA scale results. Boys in the sample proved to be addicted to video games more than girls (p = 0.041). As a result of comparing the allele frequency of DRD2 (rs6277), a tendency to a higher frequency of the minor allele T was revealed in the group of adolescents with problematic video game use compared with adolescents without problematic video game use (i. e. 0.563 and 0.466, respectively, p = 0.06). When using the dominant inheritance model, it was revealed that adolescents with problematic use of video games were statistically significantly more likely to carry the T (CT+TT) allele (p = 0.04, OR = 2.14, CI = 1.01–4.53). The T allele DRD2 (rs6277) is associated with low expression of the dopamine receptor D2 and leads to decreasing the density and affinity of extrastriatal dopamine type 2 receptors, which is associated with impaired social communication as well. We suggest that the presence of CT and TT genotypes of rs6277 DRD2 may be a potential risk factor for developing problematic video game use in adolescents.