Дилатационная кардиомиопатия (ДКМП) – одна из наиболее распространенных и клинически гетерогенных форм кардиомиопатий, для которой характерен высокий риск неблагоприятного течения и исхода. ДКМП имеет сложную этиологию, но как при семейных, так и при спорадических случаях существенный вклад в ее развитие вносят генетические факторы. В обзоре обобщается информация о роли генетических факторов в развитии ДКМП и в определении вариабельности ее клинического течения. Накопленные к настоящему времени данные свидетельствуют о высокой генетической гетерогенности ДКМП: известны многочисленные редкие патогенные варианты в более 100 генах, приводящие к развитию данного заболевания, а их тип, число и локализация могут влиять на клиническую картину болезни. Кроме того, идентифицированы распространенные генетические варианты, расположенные в различных локусах (включая регуляторные регионы генома и гены “моногенных форм” ДКМП), способные модифицировать патологический фенотип.

The advent of high-throughput sequencing technologies has expanded our understanding of the biological significance of non-coding regions of the genome. In recent years, more and more studies have been devoted to studying the role of noncoding RNAs in the development of diseases, as well as their participation in various cellular processes. Until now, all transcriptome studies of native placental tissue with the description of the noncoding RNA region were carried out without isolating individual cell populations. This approach, due to the high cellular heterogeneity of the placental tissue, significantly complicates the ability to determine the molecular-biological functions of individual cells and their role in the molecular pathogenesis of reproductive disorders. In this work, we propose a technique for obtaining total RNA from single decidual cells of frozen placental tissue obtained by laser-capture microdissection technology for transcriptome sequencing, including a cluster of noncoding RNAs. This technique can be successfully used to study the full-genome expression profile of other placental cell populations. The high accuracy of results on the transcriptome profiling of decidual cells obtained using the developed technique was additionally confirmed by an integrative analysis with the results of a 10x Genomics experiment.

Появление технологий высокопроизводительного секвенирования позволило расширить наше представление о биологической значимости некодирующих участков генома человека. В последние годы появляется все больше исследований, посвященных изучению роли некодирующих РНК в развитии болезней, а также их участия в различных клеточных процессах. До настоящего времени все полнотранскриптомные исследования нативной плацентарной ткани с описанием области некодирующей РНК проводили без выделения отдельных клеточных популяций. Такой подход, ввиду высокой клеточной гетерогенности плацентарной ткани, существенно усложняет возможность определения молекулярно-биологических функций отдельных клеток и их роли в молекулярном патогенезе репродуктивных нарушений. В представленной работе предложена методика получения тотальной РНК из единичных децидуальных клеток замороженной плацентарной ткани, полученных с помощью технологии лазерной микродиссекции, для последующего секвенирования полного транскриптома, включая кластер некодирующих РНК. Данная методика может быть успешно использована при изучении полногеномного профиля экспрессии в других клеточных популяциях плаценты. Высокая точность результатов транскриптомного профилирования децидуальных клеток, полученных с помощью разработанной методики, дополнительно подтверждается интегративным анализом с данными эксперимента, выполненного на платформе 10х Genomics.

The indigenous populations of Siberia are of significant interest for population genomics because of the specificity of their gene pools, which developed in various genetic and demographic conditions. Data on directional selection signals is an important addition to the existing data on the evolution of gene pools and the mechanisms of genetic adaptation of the population of Eurasia. We used genotype array of 1 779 819 SNPs in a group of 477 unrelated subjects, including 20 indigenous populations of Siberia, to search for directional selection signals using a test for extended homozygosity of haplotypes (nSL). The present study detected that all studied populations of Siberia strongly differ from each other in the composition of genes that demonstrate the effect of selection. The largest number of significant signals of natural selection was found in the populations of the Khanty, Koryaks, and Chukchi. The genes ADGRB3, ANO3, CDH13, CUEDC1, and PCDH15 are distinguished among the genomic loci carrying the most pronounced directional selection signals in the northern populations.

Популяции коренных этносов Сибири представляют значительный интерес для популяционной геномики по причине специфичности их генофондов, развивавшихся в различных генетико-демографических условиях. Данные о сигналах направленного отбора являются важным дополнением к существующим данным о эволюции генофондов и механизмах генетической адаптации населения Евразии. Мы использовали массив генотипов по 1 779 819 SNP в выборке из 477 человек, включающей 20 популяций коренного населения Сибири, для поиска сигналов направленного отбора с помощью теста на протяженную гомозиготность гаплотипов (nSL). Для популяций Сибири обнаружено, что все исследованные популяции сильно отличаются друг от друга по составу генов, которые демонстрируют влияние отбора. Наибольшее число значимых сигналов естественного отбора выявлено в популяциях хантов, коряков и чукчей. Среди локусов генома, несущих наиболее выраженные сигналы направленного отбора, в северных популяциях выделяются гены ADGRB3, ANO3, CDH13, CUEDC1, PCDH15.

Dysregulation of microRNA (miRNA) expression is associated with a susceptibility to many diseases, including atherosclerotic lesions of the coronary and carotid arteries and the development of clinical complications such as coronary heart disease, myocardial infarction, chronic cerebral ischemia, ischemic stroke. Recently, more and more studies analyze the miRNA regulome including a network of regulatory elements for the expression of miRNAs themselves and targets under their control. The review summarizes the data from articles concerned miRNA expression and changes in DNA methylation in the miRNA genes in human atherosclerotic arteries, as well as with the analysis of the association between single nucleotide polymorphisms and copy number variations in the miRNA genes with clinical complications of atherosclerosis.

Нарушение регуляции экспрессии микроРНК связано с предрасположенностью ко многим заболеваниям, в том числе к атеросклеротическому поражению коронарных и сонных артерий и развитию таких осложнений, как ишемическая болезнь сердца, инфаркт миокарда, хроническая ишемия головного мозга, ишемический инсульт. В последнее время появляется все больше работ, в которых анализируется регулом микроРНК, включающий сеть регуляторных элементов экспрессии собственно микроРНК и мишеней, находящихся под их контролем. В обзоре рассмотрена экспрессия микроРНК и изменения метилирования ДНК в области генов микроРНК в артериях человека при их атеросклеротическом поражении, а также проанализирована связь однонуклеотидных полиморфизмов и вариаций числа копий участков ДНК в области генов микроРНК с клиническими осложнениями атеросклероза.

The pandemic of coronavirus disease 2019 (COVID-19) warrants the identification of factors that may determine both risk and severity of infection. The factors include microRNAs that have a wide regulatory potential and hence are particularly interesting. The review focuses on the potential roles of human microRNAs and the viral genome as well as microRNAs in SARS-CoV-2 infection and clinical features of COVID-19. The review summarizes the information about the human microRNAs that are thought to specifically bind to the SARS-CoV-2 genome and considers their expression levels in various organs (cells) in both healthy state and pathologies that are risk factors for severe COVID-19. Potential mechanisms whereby SARS-CoV-2 may affect the clinical features of COVID-19 are discussed in brief. The mechanisms include blocking of human microRNAs and RNA-binding proteins, changes in gene expression in infected cells, and possible epigenetic modifications of the human genome with the participation of coronavirus microRNAs.

The pandemic of coronavirus disease 2019 (COVID-19) warrants the identification of factors that may determine both risk and severity of infection. The factors include micro RNAs that have a wide regulatory potential and hence are particularly interesting. The review focuses on the potential roles of human microRNAs and the viral genome as well as microRNAs in SARS-CoV-2 infection and clinical features of COVID-19. The review summarizes the information about the human microRNAs that are thought to specifically bind to the SARS-CoV-2 genome and considers their expression levels in various organs (cells) in both healthy state and pathologies that are risk factors for severe COVID-19. Potential mechanisms whereby SARS-CoV-2 may affect the clinical features of COVID-19 are discussed in brief. The mechanisms include blocking of human microRNAs and RNA-binding proteins, changes in gene expression in infected cells, and possible epigenetic modifications of the human genome with the participation of coronavirus microRNAs.

Detection and precise genomic mapping of balanced chromosomal abnormalities in patients with impaired fertility or a clinical phenotype represent a challenge for current cytogenomics owing to difficulties with precise breakpoint localization in the regions enriched for DNA repeats and high genomic variation in such regions. Here, we present a comprehensive cytogenomic approach to breakpoint mapping in a rare paracentric inversion on 10q (in a patient with oligoasthenoteratozoospermia and necrozoospermia) that does not affect other phenotype traits. Multicolor banding, chromosomal microarray analysis, chromosome microdissection with reverse painting, and single-copy sequencing of the rearranged chromosome were performed to determine the length and position of the inverted region as well as to rule out a genetic imbalance at the breakpoints. As a result, a paracentric 19.251 Mbp inversion at 10q22.2q23.3 was described. The most probable location of the breakpoints was predicted using the hg38 assembly. The problems of genetic counseling associated with enrichment for repeats and high DNA variability of usual breakpoint regions were discussed. Possible approaches for cytogenomic assessment of couples with balanced chromosome rearrangements and problems like reproductive failures were considered and suggested as useful part of effective genetic counseling.

The study of mitochondrial DNA (mtDNA), particularly the hypervariable segment (HVS1) region, is widely used to reconstruct a population's history, structure, and origin. The origin of the Sakha people living in the north-east of Russia has been discussed for more than 300 years, but up to the present time many aspects of their ethnogenesis remain unclear. In order to clarify the migration routes of the ancient ancestors of the Sakha, we analyzed the mitotypes of 69 unrelated representatives of this ethnic group, whose belonging to the ethnic group was traced to the third generation. In the studied Sakha group, we identified 33 mitotypes, the distribution of which by haplogroups approximately coincides with the data of other studies. The results of a comparative study of Sakha mitotypes according to EMPOP data and literature sources revealed a wide distribution of the identified mtDNA HVS1 haplotypes in many populations of Eurasia. A comparison of the obtained mitotypes with the results of mtDNA sequencing of ancient samples shows that most of the mtDNA lines of modern Sakha have long been located on the territory of Yakutia. West Eurasian and East Asian mtDNA lines were incorporated into the Sakha genome at different times in different ways. The results obtained contribute to a better understanding of the routes of ancient migrations of the ancestors of the Sakha population. © 2022, Lobachevsky State University of Nizhny Novgorod. All rights reserved.

Human ring chromosomes (RCs) are rare diseases with an estimated newborn incidence of 1/50,000 and an annual occurrence of 2,800 patients globally. Over the past 60 years, banding cytogenetics, fluorescence in situ hybridization (FISH), chromosome microarray analysis (CMA), and whole-genome sequencing (WGS) has been used to detect an RC and further characterize its genomic alterations. Ring syndrome featuring sever growth retardation and variable intellectual disability has been considered as general clinical presentations for all RCs due to the cellular losses from the dynamic mosaicism of RC instability through mitosis. Cytogenomic heterogeneity ranging from simple complete RCs to complex rearranged RCs and variable RC intolerance with different relative frequencies have been observed. Clinical heterogeneity, including chromosome-specific deletion and duplication syndromes, gene-related organ and tissue defects, cancer predisposition to different types of tumors, and reproductive failure, has been reported in the literature. However, the patients with RCs reported in the literature accounted for less than 1% of its occurrence. Current diagnostic practice lacks laboratory standards for analyzing cellular behavior and genomic imbalances of RCs to evaluate the compound effects on patients. Under-representation of clinical cases and lack of comprehensive diagnostic analysis make it a challenge for evidence-based interpretation of clinico-cytogenomic correlations and recommendation of follow-up clinical management. Given recent advancements in genomic technologies and organized efforts by international collaborations and patient advocacy organizations, the prospective of standardized cytogenomic diagnosis and evidence-based clinical management for all patients with RCs could be achieved at an unprecedented global scale.

Background: Metabolic syndrome is widespread in patients with schizophrenia receiving long-term antipsychotic therapy. Dopamine D2 receptors play an important role in mediating both the therapeutic actions of antipsychotics and their side effects. The present study examined the association of two polymorphisms of the DRD2 gene with metabolic syndrome in patients with schizophrenia.

Methods: We examined 517 patients from several regions of Siberia (Russia) with a clinical diagnosis of schizophrenia. Genotyping of two single nucleotide polymorphisms rs1799732 and rs4436578 of the dopamine D2 receptor gene (DRD2) was performed in a population of 471 patients. The results were analyzed using chi-square tests.

Results: Functional polymorphism rs1799732 of the DRD2 gene is associated with drug-induced metabolic syndrome in women with schizophrenia.

Conclusions: Our results show that the DRD2 gene may be involved in the pathogenesis of metabolic disorders in patients with schizophrenia. Further analysis of possible genetic markers will allow for personalized treatment with minimal side effects and optimal efficacy. This which seems relevant in light of the recent focus on improving the quality of life and ensuring a high level of social adaptation of patients with schizophrenia.