Vol 59, No 7 (2023)

Early prevention of development and timely diagnosis of diseases of the cardiovascular system are some of the main tasks of modern cardiology. One of the promising approaches is aimed at identifying associations between the carriage of mitochondrial DNA (mtDNA) mutations and the development of cardiovascular diseases. Mitochondria are the only source of energy accumulation in cardiomyocytes; therefore, failure of their functioning, caused by mtDNA mutations, directly affects the bioenergetics and the work of myocardial cells. The purpose of this review is to describe the current achivements in the study of associations of mutant mtDNA with the development of various pathologies of the cardiovascular system.

Genomic difference between wild allotetraploid potato species Solanum stoloniferum Schltdl et Bouchet (genome AABB) and S. tuberosum L. (AAAA) is one of the factors hampering its use in breeding. However, there is practically no information on valuable genes of this species located in the subgenome B and on the way of their transfer into the genome A of cultivated potatoes. The objectives of this research were to identify subgenomic location of a set of S. stoloniferum genes using an original approach based on a difference of inheritance of DNA markers of the genes in backcross BC₁ of chromosome doubled triploid hybrids (6x, AAAABB) to 4х S. tuberosum dependent on belonging to A or B subgenome; to study their inheritance in BC₂ and BC₃ in the framework of four introgression schemes and marker assisted selection of the gene Rpi-sto1. The markers of late blight (LB) resistance genes Rpi-sto1, R3b, R2, potato virus Y (PVY) resistance genes Ry_sto, Ry_adg were located on the subgenome B and the marker of PVY resistance gene Ry_chc – on the subgenome A. We observed an appearance of unexpected sporadic hybrids free of markers in BC₁ that may be explained by rare cases of homeological recombination of A and B subgenome chromosomes. The segregation of the markers in BC₂ (close to 1 : 1) matched in general to that expected in the case of random transfer of the corresponding chromosomes of the subgenome B. Some promising for breeding hybrids have been selected in BC₃ having the marker of the gene Rpi-sto1.

In order to study the biogeography and history of the temperate biota of the Caucasian region, one of the centers of biological diversity of Eurasia, the phylogeographic structure of the chloroplast DNA of roburoid oaks (Quercus L. sect. Quercus, Fagaceae) was studied. We analyzed 926 trees of five species (Quercus robur, Q. petraea, Q. pubescens, Q. hartwissiana, Q. macranthera) from 70 populations located in different parts of the Caucasus. Sequencing of five fragments with a total length of more than 10 000 bp revealed eight haplotypes, which were typed using chloroplast microsatellite loci (cpSSR), sequencing, and restriction analysis. The Quercus phylogenetic tree, which includes 34 chloroplast haplotypes of Western Eurasian and East Asian roburoid species, confirmed the monophyly of roburoid oaks, which form several lines that do not have supported topological relationships with each other. The haplotypes identified in the Caucasus belong to two divergent Western Eurasian lineages. These haplotypes are endemic for the Eastern Black Sea and Caucasian region and do not have related haplotypes beyond its borders, which indicates the long-term presence of oaks in the Caucasus and the historical links of the oaks of the Caucasian region with the Eastern Crimea and Eastern Turkey in the absence of chloroplast DNA exchanges with the Eastern European part of the range. The results of the present study indicate that Caucasian populations could not significantly contribute to the colonization of northern territories, and were not influenced by more northern populations, at least through seed transfer. The distribution zones of the Caucasian haplotypes almost do not intersect with each other, occupying certain geographical areas, probably due to the settlement from individual glacial refugia and genetic drift. The geographical structure of chloroplast DNA variability indicates a long-term presence of oak in addition to Western Transcaucasia (Colchis refugium), in the regions of the Northwestern, Central, Eastern Caucasus and the Lesser Caucasus. The coincident composition of the haplotypes of the studied oak species within the geographic regions indicates the long-term coexistence of different species in different parts of the Caucasus.

Variability in the number and morphotypes of macro, as well as mini and micro B-chromosomes of Apodemus peninsulae in the valley Zeya River from Amur region is described. Micro B chromosomes were found in the karyotypes of the Korean field mice from the Far East of Russia for the first time. Two opposite trends in the geographic variability of B chromosome morphotypes have been identified. The first one is due to the presence/absence of mini and/or micro, in addition to macro B-chromosomes, in animals from the right and left river banks in the northeastern part of the Upper Zeya Plain, as well as in the northern part of the Amur-Zeya Plain. The second is a clinal variability is characterized by a gradual increase in three combined geographic populations of A. peninsulae of numerical parameters of B-chromosomes: index x̄В Max micro, x̄В Max macro, the number of morphotypes, the number of clones in mosaics, and the proportion of mosaics in the direction from north to south of the Zeya River valley. The revealed diversity of A. peninsulae B-chromosome morphotypes for 13 regions allows us to re-evaluate the geographical variability of additional chromosomes of this species in the Russian Far East Adaptive value of B-chromosome morphotypes for the species has been also assumed.

Using NGS, the coding sequence of the TTN gene was sequenced in patients with left ventricular non-compaction cardiomyopathy (LVNC, 44 individuals) and hypertrophic cardiomyopathy (HCM, 74 individuals), as well as in the control (194 individuals), and 9 nucleotide variants leading to truncated titin (TTNtv) and 372 missense variants were identified. A comparative analysis of the genetic variability of titin between the groups of patients with LVNC and HCM and the control sample was carried out in terms of the type of mutations and their localization in the exons of genes, as well as in the sarcomeric and functional domains of the protein. The role of TTNtv in the development of LVNC was confirmed, and the significance of additional variants in the same gene or in other genes associated with various cardiomyopathies for the phenotypic implementation of TTNtv was demonstrated. 75% of patients with TTNtv had a dilated LVNC phenotype. Missense substitutions in the TTN gene were found both among the patients with LVNC and HCM, and in people in the control sample, which indirectly confirms that most missense variants in this gene are benign. The paper identifies and lists highly mutable and conserved exons of the TTN gene and also presents a list of missense mutations with possible clinical significance in relation to the structural pathology of the myocardium, including new variants. It was shown that the majority of pathogenic and potentially significant mutations were located in the A-zone of the sarcomere. In all the groups, about 30–50% of new variants were identified. Probably, many of them are neutral and are of exclusively population interest.

The problems of cross-contamination and swap samples are extremely relevant during large-scale genetic studies. In this study several approaches of detecting cross-contaminated DNA samples were checked: the ratio of reads per reference and alternative allele (allele ratio, AR), the amount of heterozygos to homozygous variants ratio, the CallRate value for the DNA microarrays data, the Picard CrosscheckFingerprints (CrossCheck) program. Contaminated samples (mixtures) were created by mixing ordinary “pure” DNA samples in different ratios. Samples’ quality parameters were analyzed after whole genome sequencing and genotyping with the Illumina microarray BeadArray technology CoreExome (CE) DNA microarray. It has been experimentally established that all of these approaches can be used to detect genotyping errors associated with sample contamination.

The formation of a synaptonemal complex between homologous chromosomes during prophase I of meiosis is of great importance for the normal course of the recombination process. Disturbances in the formation of the synaptonemal complex can lead to both asynapsis (in this case, univalents will be present at the metaphase I stage) and heterologous synapsis (both univalents and multivalents will be detected at the metaphase I stage). Previously, we obtained rye mutants in which no formation of synaptonemal complexes (sy1 and sy9) was observed or the synapsis was heterologous (sy10, sy18 and sy19). We performed a bioinformatics analysis of the annotated rye genome and identified potential candidate genes for each of these mutants. The choice of candidate genes was carried out on the basis of microsatellite mapping data and their comparison with annotated sequences of the rye genome. As a result, the following genes were selected: Mei2-like for the sy1 mutant, MAD2 for the sy9 mutant, BUB3.3 and BUB3.1 for sy10 and sy18, respectively, and Meiosis 5 for sy19.

Disfunction of immune system and neuroinflammation may play a role in pathogenesis of schizophrenia. The role of adaptive immune system has to be elucidated. We present a pilot study to test the methodology of profiling of immune repertoires of the TCR gamma chain by deep sequencing using several patients with juvenile schizophrenia and unaffected control subjects. The clonotype profiles were revealed and their diversity and presumable differences in structure of CDR3 TRG region of functional clones in juvenile schizophrenia and controls were estimated. This approach is perspective for further comprehensive study of changes in adaptive immune system in representative cohorts of patients with different forms of schizophrenia.