Open Access Open Access  Restricted Access Access granted  Restricted Access Subscription Access

Vol 59, No 6 (2023)

Cover Page

Full Issue

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access


Pathogenetics of Cardiomyopathy

Kucher A.N., Sleptcov A.A., Nazarenko M.S.


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.

Genetika. 2023;59(6):615-632
pages 615-632 views


The Y-Chromosome Lineage Variation in Ancient and Modern Populations of the Sakha (Yakuts)

Fedorova S.A., Zvénigorosky V., Alekseev A.N.


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.

Genetika. 2023;59(6):633-639
pages 633-639 views


Studying the Genetic Diversity of the Rice Break Cause Cav. on the Complex of Molecular and Morphological Features

Nartymov D.V., Dubina E.V., Ruban M.G., Aniskina Y.V., Garkusha S.V., Shilov I.A., Velishaeva N.S., Kolobova O.S., Istomin N.K.


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.

Genetika. 2023;59(6):640-647
pages 640-647 views


Dynamics of Rye Translocations Frequency in Russian Common Wheat L. Cultivars

Fisenko А.V., Lyapunova О.А., Zuev Е.V., Novoselskaya-Dragovich А.Y.


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.

Genetika. 2023;59(6):648-658
pages 648-658 views


Analysis of Genetic Factors of Sporadic Schizophrenia in Family Trios Using Whole Genome Sequencing

Andreeva T.V., Afanasiev P.A., Gusev F.E., Patrikeev A.D., Kunizheva S.S., Rogaev E.I.


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.

Genetika. 2023;59(6):659-669
pages 659-669 views


Elevated Level of Blood Lysosphingolipids in Patients with Schizophrenia

Kopytova A.E., Usenko T.S., Bezrukova A.I., Basharova K.S., Andreeva T.V., Volkova E.V., Manakhov A.D., Baydakova G.V., Palchikova E.I., Zakharova E.Y., Zalutskaya N.M., Neznanov N.G., Pchelina S.N.


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.

Genetika. 2023;59(6):670-675
pages 670-675 views


Impact of Chromatin 3D-Organization on Promoter–Superenhancer Interactions in Embryonic Stem vs Cancer Cells

Eidelman Y.A., Andreev S.G.


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.

Genetika. 2023;59(6):676-686
pages 676-686 views

Comparative Analysis of Structural Variant Callers on the Short-Read Whole-Genome Sequencing Data

Keskinov A.A., Yudin S.M., Skvortsova V.I., Mkrtchian A.A., Grammatikati K.S., Kazakova P.G., Mitrofanov S.I., Zemsky P.U., Ivashechkin .A., Pilipenko M.N., Svetlichny D.V., Sergeev A.P., Snigir E.A., Frolova L.V., Shpakova T.A., Yudin V.S.


In this study three structural variant callers (Manta, Smoove, Delly) were analysed on the whole-genome sequencing data using four different alignment algorithms: DRAGEN, GDC DNA-Seq Alignment Workflow, GDC DNA-Seq Alignment Workflow + GDC DNA-Seq Co-Cleaning Workflow, NovoAlign, different lengths of raw reads: 2 × 150 bp and 2 × 250 bp, different mean genome coverage values. Results were compared to etalon results of GIAB team. Structural variants validation was hold also with Sanger sequencing. Structural variants deletions and insertions as it turned out were best determined with Manta tool. We’ve got 89–96% of accuracy and 59–70% of sensitivity for analysed deletions, and also 96–99% of accuracy and 15–36% of sensitivity for insertions. Smoove and Delly showed less accurate and sensitive results (Smoove: 91–95% of accuracy and 8–54% of sensitivity for deletions, Delly: 78–87% of accuracy and 31–66% of sensitivity for deletions, 99–100% of accuracy and 1–13% of sensitivity for insertions). Simultaneous using of two or even three structural variant callers didn’t give a rise of accuracy and sensitivity for deletions. Analysis showed that accuracy and sensitivity of structural variant callers rise with the rising of mean genome coverage value, increasing of reads length from 150 to 250 bp influence in to varying degrees on the accuracy and sensitivity of individual tools. Another inference of this study was that accuracy of structural variants callers vary depends on structural variants size range. For example, Manta finds better deletions in the range from 200 and more bp, Delly – from 1000 to 10 000 bp, Smoove – from 200 to 10 000 bp.

Genetika. 2023;59(6):687-707
pages 687-707 views


About the Genetic Divergence of Populations Coupled by Migrations: Modern Modeling Based on Experimental Results of Yu.P. Altukhov and Coauthors

Zhdanova O.L., Frisman E.Y.


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.

Genetika. 2023;59(6):708-717
pages 708-717 views


DNA Repair Does Not Trigger Genetic Instability of Yeast Cells

Evstratova E.S., Petin V.G., Geraskin S.A.


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.

Genetika. 2023;59(6):718-722
pages 718-722 views

Identification of Hybrid Specimens of Rock Lizards Based on Microsatellite Genotyping

Girnyk A.E., Vergun A.A., Ryskov A.P.


The paper presents the results of microsatellite genotyping of hybrid lizards D. armeniaca × D. valentini from sympatric populations of Armenia. Triploid individuals were identified based on the totality of the Du281 and Du47G loci and their origin was determined. It was shown that the hybrids contain both alleles of the maternal parthenospecies D. armeniaca and alleles of the paternal species D. valentini.

Genetika. 2023;59(6):723-727
pages 723-727 views

Genetic Variability of Gene among Aggressive Animals from the Non-Canonical Behavioral Model

Manakhov A.D., Dudko N.A., Gusev F.E., Andreeva T.V., Trapezov O.V., Rogaev E.I.


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.

Genetika. 2023;59(6):728-732
pages 728-732 views

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies