НИИ
медицинской
генетики

Background. DNA methylation regulates numerous biological processes, mediating normal development. Alterations in methylation patterns are associated with multiple pathological conditions like hereditary diseases and cancer, making them valuable clinical biomarkers for patient stratification, disease monitoring, early diagnosis, and prediction of response to therapy. Highly targeted, high-throughput methodologies focusing on critical genomic loci enable precise identification of distinct methylation signatures. The aim of the study was to analyze and summarize literature data describing the use of high-throughput DNA methylation analysis technologies, including those based on targeted approaches. Material and Methods. A systematic analysis of literature data was conducted using the PubMed, Web of Science, and Scopus databases, focusing on the characteristics of high-throughput DNA methylation analysis used in cancer and some genetic diseases. A total of 113 sources were analyzed, chronologically covering the period from 2000 to June 2025, 32 of which were used to write the review.

Results. The existing technologies for high-throughput methylome analysis, DNA conversion methods, and their advantages and limitations were summarized. In addition, the current targeted enrichment methods, their strengths and weaknesses, and potential applications in scientific and diagnostic practice were discussed.

Conclusion. DNA methylation analysis has evolved from a basic research tool into a cornerstone of translational medicine, particularly in oncology. Modern methylome analysis techniques facilitate the discovery of epigenetic markers critical for diagnosing diseases, assessing prognosis, guiding therapy selection, and identifying molecular targets for targeted drugs. Targeted DNA enrichment increases analytical precision and sensitivity while reducing costs. Furthermore, specialized strategies permit targeted analysis even with challenging samples. Combined with the flexibility to focus on specific genomic regions, these advantages make targeted approaches viable not only in academic research but also in routine clinical diagnostics.

Using a specific case study on the classification of the Turkic languages of Southern Siberia, this paper examines the potential for combining data from linguistic and population genetic studies. Analysis of similar rules in several dialects belonging to three Turkic genealogical language groups suggests that the influence of these rules in each group is only partly related to a Sayan-Samoyedic substrate, most likely due to language shift that is, the transition of the Sayan Samoyedic people to several Turkic languages. A similar hypothesis was previously proposed by A. Dulzon (Andreas Dulson), but it has not been supported by comparative historical analysis. For Northern Altaic idioms, it appears more likely that the Sayan Samoyeds themselves did not transite to these lects, but rather that a secondary language shift occurred among the Shors, who were already Samoyeds at that time and had adopted a Turkic language. Population genetic data support this hypothesis.

Aim. To assess the relationship between the respiration of mitochondria of peripheral blood leukocytes and mitochondrial DNA (mtDNA) polymorphism in patients with coronary heart disease (CHD) depending on the risk of developing sudden cardiac death (SCD).Materials and methods. We formed two groups of patients: the main group - patients with CHD and the high risk of SCD (n = 107); the comparison group - patients with stable course of CHD without the risk of SCD (n = 50). Using methods of high-throughput sequencing, we determined patients’ haplogroup and carriage of mtDNA polymorphisms A2706G, G3010A and G9055A. The respiratory activity of isolated mitochondria from peripheral blood leukocytes was assessed by amperometric method using NADand FAD-dependent oxidation substrates.Results. In both studied groups, H, U, and J haplogroups were predominant (74.5% and 92.5%, respectively, for the main group and the comparison group). There were more minor haplogroups in the main group than in the comparison group. The frequencies of occurrence of polymorphisms A2706G, G3010A, and G9055A did not significantly differ between the groups. In the main group, carriage of the A2706G polymorphism was associated with a decrease in the respiratory control ratio (RC) in FAD-dependent respiration (p = 0.05), and in the comparison group it was associated with a decrease in oxygen consumption rate (OCR) in the V4 metabolic state in both NADand FAD-dependent respiration (p = 0.002 and p = 0.008, respectively) without changing in RC. In the main group, carriage of the G9055A polymorphism was associated with a decrease in OCR in the V3 metabolic state (p = 0.037) in FAD-dependent respiration. For the G3010A polymorphism, no association with mitochondrial respiration was found in the studied groups.Conclusion. In patients with CHD, regardless of the risk of SCD, the frequencies of haplogroups H, U, and J and mtDNA polymorphisms A2706G, G3010A, and G9055A do not differ significantly. In patients with high risk of SCD, carriage of the A2706G polymorphism is associated with a decrease in RC in FAD-dependent respiration, and the G9055A polymorphism is associated with a decrease in OCR in V3 during FAD-dependent respiration.

Introduction . Aortic arch anomalies, especially the “bovine arch”, can cause the development of an ascending aortic aneurysm. There is a high coefficient of heritability of this pathology, however, genetic studies are rare. Since the “bovine arch” is one of the variants of the development of the aortic arch and large vessels during embryogenesis, this pathology may be associated with genes encoding proteins involved in the embryonic development of the cardiovascular system. Aim: To identify rare, clinically significant variants of genes of cardiovascular embryonic development in patients with sporadic ascending aortic aneurysm and a “bovine arch”. Material and Methods . The study included 42 patients with a sporadic form of ascending aortic aneurysm, including 11 patients with a “bovine arch”. Analysis of the clinical exome was performed based on DNA sequencing data using Clinical Exome Solution (Sophia Genetics, Switzerland) and NextSeq 500 genetic sequencer (Illumina, USA). The search for rare, clinically significant variants (minor allele frequency <1%) was carried out in exons and adjacent introns of 120 genes of embryonic development of the cardiovascular system. Validation of identified variants was performed using Sanger sequencing. Results. In patients with aortic aneurysm and “bovine arch”, the following clinically significant variants were identified: the pathogenic variant c.610-2A>G of the CCDC39 gene, which is a single-nucleotide substitution leading to the loss of the acceptor splice site (ΔScore = 0.97 Spliceailookup) and a variant of uncertain clinical significance (VUS) c.2564T>C in the ANKS6 gene, which has high pathogenicity rates on the CADD (Phred = 28.3) and AlphaMissense (0.972) scales. A likely pathogenic variant c.1151T>C of the ACVR2B gene was identified in the group of patients with aortic aneurysm without supraaortic vessels anomaly (AlphaMissense = 0.966). Among the 38 genes whose sequences revealed VUS in both groups of patients, the protein products of 17 (44.7%) are involved in the functioning of cilia and microtubules, and the proteins encoded by the genes MKS1, CCDC40, DNAAF1, ANKS6, CCDC39, DNAH5, DNAAF3 are also responsible for the development of the cardiovascular system. Conclusion . Rare, clinically significant variants in the CCDC39 and ANKS6 genes, which are crucial for primary cilia function, contribute to the development of sporadic ascending aortic aneurysm in combination with a “bull’s arch.” When a normal aortic arch is present, variants in the ACVR2B gene, belonging to the TGF-beta signaling protein superfamily, play an important role.