Genetika

This review summarizes the current state of knowledge on the genetic factors of both primary or Mendelian cardiomyopathies (CMPs) and some of its secondary forms. Dozens of genes with pathogenic/probably pathogenic variants have been described for primary CMPs. In most cases, the spectrum of causal genetic variants is specific for different CMPs, but shared genes and variants are also discovered. On the one hand genetic causes of diseases have not been established for all cases of primary CMPs, but on the other hand pathogenic variants in Mendelian disease genes are also found for its secondary forms. The genetic component in the development of both primary and secondary CMPs was also established during genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) associated with both primary and secondary CMPs are in most cases specific for different types of disease and make a small contribution to an individual’s overall risk. The link between some SNPs and electro- or echocardiogram features of the normal heart has been reported in the population. Most of the CMPs-associated SNPs are localized in non-coding regions of the genome, but they have a regulatory potential, acting in the heart as loci that affect the level of expression (eQTL), splicing (sQTL) or epigenetic modifications. It is noteworthy that the effects of the eQTL and sQTL genotypes in some cases are not equivalent for different anatomical regions of the heart. The phenotype and clinical presentation of CMPs in general can be determined by a wide range of rare pathogenic/probably pathogenic variants with a strong effect and common polymorphisms with a small effect and modified by epigenetic factors.

This review presents the results of paleogenetic studies on the ancient population of Yakutia in the Middle Ages. The diversity of haplogroups and STR haplotypes of the Y chromosome of 74 men from Yakut burials from the 15th–19th centuries was considered and compared with the data on modern ethnogeographical groups of the Yakuts. A comparison of genetic reconstructions with historical data and the legends of the Sakha people was performed.

On the basis of molecular genetic approaches, the study of the biodiversity of the phytopathogenic fungus Pyricularia oryzae Cav. in the south of Russia and a classification of the morphological and cultural characteristics of the pathogen was carried out. For 2020–2022 monitoring was carried out and 24 strains of the pathogen were isolated from the affected herbarium material collected from the fields of five ecological rice growing zones of the Krasnodar Territory (Krasnoarmeisky, Kalininsky, Abinsky, Slavyansky districts, Krasnodar). Using the multiplex PCR system developed by us based on fragment analysis, five genotypes were identified among the studied Pyricularia oryzae Cav. strains over the entire period of the project, each of which is characterized by a unique genetic profile. Compiled their “DNA passport”. The studied isolates of the causative agent of blast were characterized by morphological and cultural characteristics. Six morphotypes of the pathogen have been identified.

The widespread using 1RS/1BL and 1RS/1AL translocation cultivars in wheat breeding was due to their high complex resistance provided by genes on 1RS chromosomes. Numerous data on the emergence of new virulent pathogen races that caused the loss of protective properties by genes on 1RS make it relevant to analyse the prospects for using both rye translocations in modern breeding programs. The use of various genetic sources of the 1RS rye chromosome in introgressive hybridization poses the problem of studying the diversity of 1RS linkage groups. We have studied the rye translocations dynamics in 240 genotypes of the wheat cultivars from 3 breeding centers of the Russian Federation. Multiple alleles of storage protein genes specific for 1RS were used to mark 1RS. The effectiveness of 1RS resistance genes to a number of pathogens, in particular to powdery mildew and stem rust, has been established. The grain quality dynamics of the 1RS/1BL cultivars has been traced. A statistically significant grain quality improvement of winter wheat cultivars since the 2000s has been confirmed. The spring cultivars quality does not depend on the presence of rye translocations in the genotypes. Accumulation of cultivars with TR:1RS/1BL observed in all three centers. A high allelic diversity of the secalin coding locus on 1RS chromosome was shown. However, all cultivars with rye translocations, regardless of 1RS origin, carried the same allele. Possible reasons for this uniformity are discussed. Translocation 1RS/1AL was not detected in the studied cultivars. Possible reasons are discussed.

Schizophrenia is a mental disorder, the hereditary nature of which has been confirmed by numerous studies. Currently, more than a hundred genetic loci associated with schizophrenia have been described, and rare variants in genes and chromosomal rearrangements associated with familial cases of the disease have also been identified. However, it is not always possible to determine the hereditary nature of the pathology, many cases of schizophrenia are sporadic, and the genetic cause of such cases remains unknown. Using whole genome sequencing data for three family trios from Russia with sporadic cases of schizophrenia, we searched for rare potentially pathogenic variants in the coding and regulatory loci of the genome, including de novo and compound mutations. The polygenic risk of schizophrenia was also assessed using common polymorphic markers. As a result of the analysis, the genetic heterogeneity of sporadic forms of schizophrenia was shown, as well as the potential role of rare substitutions in genes associated with the metabolism of glutamate and inositol phosphate in sporadic cases of schizophrenia.

Schizophrenia is a mental disorder with a prevalence of 0.7–1% of the general population and is characterized by impaired dopamine transmission in neurons. Recent data have shown that lysosomal storage disorders (LSD), characterized by a decrease in enzyme activity and a corresponding accumulation of substrate in lysosomes due to mutations in lysosomal genes, can manifest a wide range of clinical symptoms including psychosis, affective disorders, early onset dementia and schizophrenia. The purpose of this study was to assess the level of lysosphingolipids in patients with schizophrenia, Parkinson’s disease (PD) and control. The study included 52 patients with schizophrenia, 170 patients with PD patients and 166 neurologically healthy individuals (control group). Concentration of lysosomal substrates (hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), lysosphingomyelin (LysoSM)) were measured by high-liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) in blood. An increase in the concentration of LysoSM, LysoGb3, HexSph was detected in patients with schizophrenia compared to control (p < 0.0001, p < 0.0001, p < 0.0001, respectively). Our results confirm a violation of the lysosphingolipid composition of the blood in patients with schizophrenia.

The interaction of enhancers and superenhancers (SE) with promoters is functionally significant for the regulation of gene expression. Pattern of these interactions plays a key role in various processes, such as differentiation, malignant transformation, etc. In order to quantify the relationship between 3D chromatin organization and promoter–SE contacts, a computational analysis of chromatin conformations near the murine Nanog pluripotency gene was performed for normal embryonic stem (mESC) and lymphoma (CH12LX) cells. Using biophysical modeling approach, the following parameters of the promoter–SE interactions were identified: the distribution of distances between the Nanog promoter and the SEs, the frequency of contacts with one and several SEs simultaneously. In normal mESC expressing Nanog, the frequency of contacts of promoters with SEs is higher than in cancer cells, and complex contacts with two or more SEs are more frequent. The modelling reveals a small subpopulation of cancer cells, where the promoter contacts simultaneously three SEs. The predicted subpopulation of cancer cells with multiple promoter–SE contacts may be predisposed to increased stemness and hypothetically be considered as a reservoir for generation of cancer stem cells.

The existence possibility of stable differences in a selection-homogeneous range looks somewhat paradoxical from the population genetics point of view, but it is disruptive selection that can give such a divergence. Examples of population systems with stable divergence of the genetic structures of subpopulations living in a homogeneous area occur in nature and experimental systems. Comparison of these observations and modeling results allow us to explain the persistence of the stability of natural genetic divergence by the mechanism of interaction between disruptive selection (in the form of reduced fitness of hybrid forms) and a weak migration process. The results of experiments performed by Yu.P. Altukhov et al. with box populations of Drosophila melanogaster, in which the primary divergence of the genetic structures of the subpopulation at the α-GDH locus appeared, are in good agreement with this statement. One can assume the disruptive selection, in this case, the reduced fitness of heterozygotes in α-HDG, played the significant role in maintaining this divergence. An alternative hypothesis is genetic drift that fixed the differences. To identify and substantiate the possibility of the presence of this factor in a given system, and to assess the significant role that disruptive selection plays in maintaining the stability of primary genetic divergence, we analyzed mathematical models of the allele frequencies’ dynamics in a large panmictic population and in a system of 30 local migration coupled populations. Comparison of the simulation results with those of the experiment allows us to conclude with a high probability, in the considered experimental population system, there was a disruptive selection at the α‑GDH locus that facilitated the primary genetic divergence.

The dependence of the delayed formation of colonies on the dose of ionizing radiation (gamma rays of ⁶⁰Co, dose rate 10 Gy/min) was obtained for six strains of wild-type haploid and diploid yeast, capable of recovering from radiation damage and characterized by sigmoidal survival curves as well as for six haploid and diploid radiosensitive mutants defective in reparation and characterized by exponential survival curves. The delay in the formation of colonies by survival cells after irradiation is considered as a genetic instability display. It was shown that for all diploid strains, genetic instability reached 100% with an increase in the dose of ionizing radiation, regardless of the shape of survival curves and the cell ability to recover from radiation damage. Conversely, for all haploid strains, genetic instability was only close to 20%. In contrast to traditional concepts, these data indicate that the late formation of colonies by surviving yeast cells after irradiation is determined mainly by cell ploidy and does not depend on the shape of the dose-response curves and cell radiosensitivity. This means that DNA repair does not trigger genetic instability in yeast cells.

The MAOA gene is widely known regulator of aggressive behavior among human and animals. Here, we analyzed the genetic variability of the MAOA gene and its promoter region in non-canonical behavioral model – American mink (Neogale vison). We didn’t observe any significant genetic variations among animals with aggressive behavior, that suggests the presence of genetic and/or epigenetic variations in other systems involved in regulation of aggression in this model.