Alzheimer’s disease is the most common form of neurodegenerative dementia characterized by β-amyloid accumulation, tau protein hyperphosphorylation, and pronounced glial activation. Despite extensive investigation of its pathogenesis, effective disease-modifying treatments remain limited. In recent years, rare genetic variants associated with innate resistance to Alzheimer’s disease have attracted growing attention. Among them, the APOE3 Christchurch and RELN-COLBOS variants identified in carriers of the PSEN1 Glu280Ala mutation in Colombian families with autosomal dominant Alzheimer’s disease are of particular interest. In these individuals, the onset of cognitive impairment was delayed by more than two decades compared to typical cases, suggesting the existence of endogenous neuroprotective mechanisms. This review summarizes current data on the role of APOE and RELN variants in the regulation of the Reelin– ApoE signaling cascade, involving DAB1, AKT, and GSK3β proteins that control tau phosphorylation and synaptic plasticity. Potential mechanisms by which these genetic factors modulate microglial and astrocytic activity and preserve synaptic integrity are discussed. Understanding the molecular basis of brain resistance to Alzheimer’s disease provides promising avenues for the development of new pathogenetic strategies aimed at modulating Reelin–ApoE-dependent pathways and preventing neurodegeneration.

Myotonic dystrophy type 2 is a multisystem neurodegenerative disorder with an autosomal dominant inheritance pattern, traditionally considered to have an onset in the 3rd or 4th decade of life. This paper describes clinical cases of myotonic dystrophy type 2 manifested before age of 18. The authors suppose that reviewing these cases will contribute to improved understanding of the phenotypic manifestations and early diagnosis of this disorder.

We report a clinical case of pregnancy-associated breast cancer (PABC) in a woman carrying the pathogenic CHEK2 c.1100delC variant. The tumor was diagnosed postpartum and initially misinterpreted as lactostasis, which led to a delay in diagnosis at an advanced tumor size. The patient received a combined treatment regimen with a complete metabolic and pathological response, followed by confirmation of a hereditary cancer predisposition. This case highlights the biological features of PABC and the clinical implications of CHEK2 pathogenic variants, including elevated risk of contralateral breast cancer. The need for a personalized approach in diagnosis and treatment of young women with PABC is emphasized. The findings support the inclusion of the CHEK2 c.1100delC variant in standard PCR screening panels and underscore the lack of standardized guidelines for managing hereditary PABC cases.

This brief report presents the results of a transcriptome profile analysis of colon tumors and liver metastases during FOLFOXIRI chemotherapy in patients with metastatic colon cancer (mCRC). Whole-transcriptome sequencing was performed on the DNBSeq platform using the DNBSEQ-G400RS High-throughput Sequencing Kit (MGI, China). Transcriptome transformation of primary colon tumors and liver metastases during preoperative FOLFOXIRI chemotherapy in combination with targeted therapy was demonstrated. A potential panel of candidate genes, such as IL1RN, DUSP1, NAMPT, IL7R, PCSK9, DGAT1, EPS8L2, and FOS that are involved in metastasis and response to FOLFOXIRI was identified.

Shift work is a significant risk factor for human maladaptation and early myocardial remodeling. The prevalence of hypertension (HTN) is 47% among men with shift work in the Arctic. Hypertension quickly harms vital organs and can lead to heart failure. An association between TNNT2 gene polymorphisms and echocardiographic parameters was previously reported in patients with hypertrophic cardiomyopathy. Objective: To examine associations between common genetic variants of the TNNT2 gene and echocardiographic parameters in shift workers with HTN in the Arctic area. A total of 190 males (18-70 years old) were included. DNA samples were genotyped using a real-time polymerase chain reaction. As a result, rs1104859, rs3729547, and rs10920184 demonstrated a statistically significant association with several echocardiographic parameters (left atrial strain, posterior wall thickness, left ventricular volume, and interventricular septal thickness). This suggests the potential for using genotyping to predict the clinical course of early myocardial remodeling in shift workers with HTN in Arctic area.

The article presents the results of a study of the variability of the population structure of the Belgorod region from 1999 to 2019. The material for the study was data on the frequencies of 28574 surnames of the entire population (more than 1.5 million people) of the Belgorod region in 2019 compared to 1999 data. Over 20 years, the population of the region decreased by an average of 12%, the number of surnames – by 34%, the level of migration influx increased by 4.8 times, leading to a 22.7% increase in random inbreeding. Significant factors in the variability of the population structure of the region over two decades, estimated on the basis of data on surnames, remained the level of migration influx of the population and the degree of development of transport infrastructure.

In megalopolis, the main factor of dynamics of the gene pool is migration. In two generations of Moscow residents and, also, in the samples from Saint-Petersburg and Novosibirsk, 18 STR of Y-chromosome were studied, by obtained haplotypes Y-chromosome haplogroups were predicted using Internet-predictor Whit Athey’s. In two generations of Muscovites, 27 autosomal STR, not included in the system CODIS, were studied. In comparison of the sample from Novosibirsk with the samples from Saint-Petersburg and the young sample from Moscow, statistically significant estimates of genetic differentiation (FST) by profiles of 18 STR Y-chromosome were observed. For two samples of Muscovites, FST value by 18 STR of Y-chromosome was substantially higher, than the value of FST obtained by autosomal STR. The results of the investigation by DNA-markers of Y-chromosome (18 STR, haplogroups) and 27 autosomal STR demonstrate validity of specific approach for developing reference data bases for megalopolises by different DNA-markers, mediated by individual dynamics in generations. Obtained results support necessity of developing separate data bases for each megalopolis for DNA-identification and their timely update depending on gene pool dynamics in generations under action of migration.

In genome-wide association studies, single-marker and multi-marker approaches are distinguished. Single-marker methods analyze each single nucleotide polymorphism (SNP) individually, which allows for rapid identification of genetic markers associated with a phenotype. Multi-marker methods consider combinations of SNPs, which increases the power of tests and the overall informative value of the analysis, although it also increases the computational load. Previously, we proposed breaking down the linkage disequilibrium matrix into singular submatrices, using the matrix determinant as a measure of SNP correlation within a group. By applying this approach to the genotypes of individuals from Western Europe (4929 patients with ischemic stroke, 652 control individuals, 883,749 SNPs), we identified candidate genes for the disease that were not detected by single-marker methods. In this work, we reapplied this method to the same sample of individuals but using 10 times more SNPs obtained by enriching the original marker panels through imputation. The study results demonstrated the applicability of the determinant method for analyzing large SNP datasets, including those obtained via imputation, and suggested a potential role of neurogenesis in the development of ischemic stroke.