Approximately 10–15 % of clinically recognized pregnancies result in miscarriage, with chromosomal abnormalities identified in about 50 % of early pregnancy losses (PL). Triploidy accounts for approximately 12 % of all chromosomal abnormalities in miscarriages. The additional haploid set of chromosomes in triploidy may be of paternal (diandric tri ploidy) or maternal (digynic triploidy) origin. Diandric triploidy is associated with a partial hydatidiform mole (PHM), while pregnancies involving diploid embryos with two paternal genomes (and loss of the maternal nuclear genome) are the most common cause of a complete hydatidiform mole (CHM). The hydatidiform mole (HM) is the most prevalent form of gestational trophoblastic disease. Genotyping of products of conception (POC) is currently considered a reliable method for confirming HM and distinguishing its subtypes.

   The aim of this study was to use DNA genotyping of POCs to detect cases of triploidy, estimate the frequency of HM and its subtypes, and analyze the molecular and clinical characteristics of triploid pregnancies, CHM, and PHM in a Russian population.

   Between 2018 and 2024, a total of 10,000 consecutive PL cases were analyzed at the Medical Genetic Center Progen (Moscow). The main clinical indications included spontaneous miscarriage, missed miscarriage, and anembryonic pregnancy. DNA genotyping was performed using a five-color multiplex QF-PCR method, which included profiling of 26 autosomal STR markers, as well as DYS437, DXS6809, the SRY gene, and 30 markers from homologous regions located on different chromosomes. CHM was diagnosed based on the homozygosity of all STR markers. Triploidy was identified by analyzing peak area ratios of non-homozygous STR markers, which exhibited characteristic patterns of approximately 2:1 or 1:1:1. In our cohort, chromosomal abnormalities were identified in 58.8 % of all PL cases. Triploidy was detected in 8.3 % of the total sample, representing 14.3 % of all chromosomally abnormal POCs. Diandric triploidy accounted for 43 % of triploid cases. The prevalence of CHM was 0.11 %. The median age of women with triploidy was 32.1 years, and 27.9 years for those with CHM. Given the observed frequencies of PHM and CHM in our cohort, along with the relatively young maternal age associated with these conditions, enhancing current diagnostic protocols for HM – particularly through the incorporation of DNA genotyping of POCs – is essential for the effective prevention and timely diagnosis of post-molar malignant neoplasms in this population.

   Uniparental disomy of chromosome 9, in combination with low-level mosaicism for chromosome 9, represents a rare chromosomal disorder. One of the mechanisms underlying the formation of uniparental disomy is the trisomy rescue, which concurrently results in low-level mosaicism. The diagnosis of mosaic aneuploidies poses significant challenges due to the limited sensitivity and resolution of conventional cytogenetic methods, which often fail to detect low-level mosaicism. Additionally, the variable distribution of cell lines within the patient’s tissues, as well as the heterogeneity of samples derived from the same tissue, complicates the precise determination of the impact of mosaic trisomy on the phenotypic expression. Phenotypic manifestations associated with mosaic trisomy 9 are characterized by considerable variability. During the prenatal period, intrauterine growth restriction is frequently observed in cases of this chromosomal abnormality, although this finding is not pathognomonic for the condition. In liveborn infants with trisomy 9 mosaicism, characteristic phenotypic features may include craniofacial anomalies (such as micrognathia and ear malformations), scoliosis, low-set ears, feeding and respiratory difficulties, hip dysplasia, seizures, and developmental delays. To establish a diagnosis in a patient presenting with multiple dysembryogenic stigmata and psychomotor retardation, a comprehensive molecular cytogenetic analysis was conducted. This included high-resolution chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) using targeted DNA probes. CMA identified regions of loss of heterozygosity (LOH) on chromosome 9, indicative of uniparental disomy, and suggested the presence of low-level mosaicism for trisomy 9. Subsequent FISH analysis of cultured lymphocytes, employing DNA probes specific to various regions of chromosome 9, confirmed the low-level mosaicism for trisomy 9. The results of our study are consistent with the idea that mosaicism for chromosome 9, particularly when combined with uniparental disomy, constitutes a complex genetic anomaly that can lead to a spectrum of phenotypic manifestations, including developmental delay, growth abnormalities, and behavioral anomalies. CMA and FISH are highly effective methods for the diagnosis of uniparental disomy and low-level mosaicism involving chromosome 9.

   Genetic factors contribute to the etiology of intellectual disability in 25–50 % of cases. Chromosomal abnormalities, such as microdeletions and microduplications, are the most significant genetic causes. We examined a family where two boys, aged 8 and 7, were diagnosed with mild intellectual disability. Using array-based comparative genomic hybridization, we detected a duplication of Xq28 in both brothers on the X chromosome inherited from a healthy mother with skewed (88 %) X-chromosome inactivation. The size of the rearrangement is 439.6 kilobases (kb). Eight genes are located in this region, including F8, MTCP1, BRCC3, VBP1, RAB39B, CLIC2, FUNDC2, and CMC4. This chromosomal region overlaps with the region of Xq28 duplication syndrome (OMIM 300815), characterized by intellectual disability, behavioral and psychiatric disorders, recurrent infections, atopic diseases, and specific facial features in affected male individuals. Whole-exome sequencing did not reveal pathogenic or likely pathogenic variants associated with neurodevelopmental disorders. These disorders have been previously linked to X-linked recessive single-nucleotide variants in RAB39B (OMIM 300271, 311510) and CLIC2 (OMIM 300886). An assessment of the clinical significance of the identified duplication, using the AutoCNV internet resource and original data, allowed us to classify this variant as pathogenic. This implies that the identified duplication may be the cause of intellectual disability in patients.

   Interstitial deletions of the short arm of chromosome 6 are even rarer than distal deletions of 6p24-pter, with an incidence rate of 1:1,000,000 (according to MalaCards, https://www.malacards.org/). These deletions are associated with developmental delays, autism spectrum disorders, congenital anomalies, and dysmorphic features.

   The objective of our study was to identify chromosomal abnormalities in twins from a Yakut family exhibiting severe psycho-speech developmental delays, intellectual disability combined with dysmorphisms, and congenital anomalies.

   In this paper, two new cases involving monozygotic twins from a Yakut family, who underwent array comparative genomic hybridization (aCGH), were reported. The diagnostic results revealed a rare interstitial deletion in the region 6p22.3-p24.3, measuring 7.5 Mb, which was subsequently confirmed using a conventional cytogenetics (GTG-banding) method. According to the cytogenetic analysis, the karyotypes of the parents were normal, indicating a de novo structural chromosomal rearrangement in the patients. Additionally, a comparative phenotypic analysis of these twins with each other and with other previously reported patients was performed; they were found to have overlapping deletions in the 6p22-p24 region. Furthermore, a literature review and an analysis of the gene content of the deleted region 6p22.3-p24.3 were conducted, and so was a discussion of the genotype-phenotype correlation. The results of the phenotypic analysis revealed both common and distinct dysmorphogenic features, including craniofacial dysmorphisms, deformities of the auricles, and abnormalities in the development of the upper and lower limbs, which are often mentioned in the literature. However, the analyzed data, both from the literature and our observations, showed that all patients lacked a common deleted region in the 6p22-p24 area, creating challenges in establishing an accurate diagnosis. The findings indicate the complexity of defining the minimally overlapping region responsible for the observed phenotypic and behavioral traits and highlight the importance of a systematic and multi-level approach to diagnosing severe psycho-speech developmental delays.

   A paracentric inversion (PAI) is a rare type of balanced intrachromosomal structural rearrangement. Heterozygotes for PAI are usually phenotypically normal, but the presence of the inversion may occasionally lead to synapsis and recombination disruptions during meiosis. PAI can be responsible for the production of recombinant chromosomes and unbalanced gametes. The risks associated with the birth of a child with chromosomal imbalances due to the generation of unbalanced crossover gametes is considered to be low. Nonetheless, viable offspring with intellectual disabilities and/or congenital abnormalities, as well as early miscarriages, stillbirth and infertility in heterozygous carriers of PAI have been described. Paracentric inversions may arise on various chromosomes. PAI with breakpoints on the long arm of chromosome 7 is among the most prevalent ones in humans. To assess the meiotic behavior of abnormal chromosome 7, as well as the empirical risk of producing gametes with recombinant chromosomes, the sperm FISH analysis of a male heterozygous carrier of inv(7)(q11.23q22) was performed. The percentage of recombinant sperms was 0.7 % and chromosomal imbalance was represented as reciprocal breakage products of a dicentric chromosome 7. Notably, spermatozoa with a dicentric chromosome 7 were not observed, which confirms its instability during meiosis I. Meiotic segregation analysis in the heterozygous carrier of inv(7)(q11.23q22) revealed a predominant formation of gametes containing either the inverted or the intact chromosome 7, occurring at frequencies of 52.2 and 47.8 %, respectively. This report is the first study providing a detailed description of meiotic segregation patterns of inv(7)(q11.23q22) by using a sperm FISH approach. Recombinant gamete formation confirms the occurrence of crossing-over within the inversion loop. Consequently, the individual risk of generating gametes (and subsequent zygotes) with chromosome 7 imbalance for this heterozygous carrier remains low.

   Reciprocal translocations are the most common structural chromosomal rearrangements, occurring at a frequency of 0.08–0.3 % in the human population. The vast majority of carriers of reciprocal translocations are phenotypically normal, but have an increased risk of miscarriage or the birth of children with intellectual disabilities and multiple congenital abnormalities due to meiotic malsegregation of chromosomes involved in the translocation. This study presents a familial case of translocation involving the distal regions of the short arms of chromosomes 3 and 10, detected in seven family members across three generations. The investigation was prompted by the detection of a deletion 10p15 and a duplication 3p25 revealed through clinical exome sequencing in a proband exhibiting phenotypic abnormalities, which may correspond to der(10)t(3;10)(p25;p15). GTG cytogenetic study of the proband’s family revealed that the mother, grandmother, aunt and brother – none of whom displayed any clinical or phenotypic manifestations – were carriers of a balanced chromosomal rearrangement, t(3;10)(p25;p15). By contrast, the karyotype of the proband’s sibling – a girl with severe cognitive, neurological, and developmental abnormalities – was found to be 46,XX,der(3)t(3;10)(p25;p15)dmat. Molecular karyotyping facilitated further clarification of the chromosomal imbalance and the precise breakpoints on both chromosomes involved in the translocation. This study provides a detailed description of the clinical and phenotypic manifestations resulting from the presence of derivative chromosomes 3 and 10 in the karyotype. Additionally, it discusses the mechanisms underlying the formation of chromosomal imbalances in the family members with the abnormal phenotype, the relationship between the severity of clinical manifestations and changes in gene dosage due to chromosomal rearrangements, as well as potential preventive and rehabilitative measures aimed at reducing the risk of chromosomal pathology in the families with carriers of autosomal reciprocal translocations.

   Transposable elements (TEs), comprising over one-third of the human genome, play a crucial role in its evolution, serving as a significant source of regulatory sequences. Under normal circumstances, their activity is tightly controlled by DNA methylation mechanisms; however, the effectiveness of this suppression varies substantially across tissues. The placenta, characterized by global hypomethylation, represents a unique environment where retroviruses and retrotransposons, typically silenced in somatic cells, gain the opportunity for activation. This distinct epigenetic landscape of the placenta allows transposons to participate in the regulation of genomic activity, influencing processes ranging from early embryogenesis to postnatal development. DNA hypomethylation in the placenta not only promotes TE mobilization, but also opens the possibility of using their components as independent genes and regulatory elements – promoters, enhancers, and other functional modules. These elements are involved in key aspects of placental development, including syncytiotrophoblast formation, extravillous trophoblast invasion, spiral artery remodeling, and endometrial decidualization. Importantly, TEs can serve as sources of alternative promoters for neighboring genes, and ancient mammalian transposons contain multiple transcription factor binding sites, enabling coordinated regulation of genes sharing a common function. Despite the growing interest in the role of transposable elements in placental development and function, many questions remain unanswered. In particular, the mechanisms of non-long terminal repeat (non-LTR) retrotransposon function during pregnancy remain poorly understood. A deep understanding of these processes is necessary to elucidate regulatory disorders in the placenta associated with major obstetric syndromes. This review examines the contribution of transposable elements to the functioning of the human genome, particularly their impact on gene expression, in the context of pregnancy and placental development.

   Human mitochondrial DNA (mtDNA) exhibits high population-level polymorphism. While certain pathogenic mtDNA variants are known to cause hereditary mitochondrial syndromes, often presenting with cardiac arrhythmias, life-threatening ventricular tachycardia (VT) itself is a major risk factor for sudden death in cardiovascular diseases.

   The aim of the work was to study rare (“private”) missense substitutions in the mtDNA of patients with documented episodes of ventricular tachycardia in comparison with patients with ischemic heart disease without life-threatening heart arrhythmias and individuals without clinical manifestations of cardiovascular diseases.

   The sequencing of mtDNA was performed using high-throughput sequencing methods. Specialized algorithms predicting the effect of gene variants were used to assess the effect of missense substitutions. Comparative analysis of the spectrum of the identified amino acid substitutions in the studied groups showed that about 40 % of the individuals in all three groups were carriers of “private” missense variants in mtDNA. However, among such substitutions, the variants classified by the APOGEE2 predictor as “variants of uncertain significance” (VUS) were more common in the group of patients with heart arrhythmias than in the control group, where “private” missense substitutions of the VUS category were not detected (p = 0.0063 for Fisher’s exact test). In addition, the groups differed in their phred-ranked Combined Annotation Dependent Depletion (CADD) scores, which were lower for individuals in the control group. The results indicate that rare mtDNA variants may contribute to predisposition to cardiovascular disease – in particular, to the risk of developing ventricular tachycardia by some patients.

   Crouzon syndrome, which is a hereditary craniosynostosis, can be the result of inheritance from either pa­rent, as well as de novo mutations in the FGFR2 gene. With a confirmed molecular genetic diagnosis, preimplantation genetic testing for monogenic diseases (PGT­M) is available for high­risk families. However, there is currently little information in the literature about using this approach to prevent this condition.

   The aim of our study was to de­ scribe the clinical case of IVF/ICSI with PGT­M for Crouzon syndrome with a successful outcome and confirmatory diagnostics. PGT­M was planned and performed for a married couple (aged 24 and 25), in which the husband had Crouzon syndrome.

   The husband’s father had a milder form of Crouzon syndrome and the pathogenic variant of the FGFR2 gene was in a mosaic form. During preparation, a testing system was selected for the pathogenic variant
NM_000141.5(FGFR2):c.1007A>G (p.Asp336Gly) of the FGFR2 gene, and gene­linked polymorphic microsatellite mar­kers. The STR markers in the husband’s father excluded chimerism for the pathogenic variant and indicated mosaicism with the involvement of germ cells. Molecular genetic analysis was performed using а nested PCR, with detection by fragment analysis for STRs and restriction analysis of the pathogenic variant. During the IVF program, superovula­ tion stimulation and embryological procedures were performed according to standard protocols. Fertilization was achieved using the ICSI method, and blastocyst biopsy was done on the sixth day of development. For PGT­M, a direct analysis of pathogenic variants and an indirect analysis of selected informative STRs were used. The thawed embryos were transferred based on the results of preimplantation testing. We selected twelve STRs flanking the FGFR2 gene, eight informative ones were used during PGT­M. In the IVF program, 15 mature oocytes were obtained, then four blastocysts were biopsied. One of the four embryos inherited a normal paternal chromosome, the other three had the pathogenic variant and the associated risk haplotype. A singleton pregnancy has occurred as a result of embryo transfer recommended after PGT­M. Following the child’s birth, molecular diagnostics were performed, confirming the PGT­M result. The presented clinical case provides an effective example of IVF with PGT­M to prevent the birth of affected children in families with hereditary craniosynostosis.

   Genetic mechanisms regulating gene expression encompass complex processes such as transcription, translation, epigenetic modifications, and interactions of regulatory elements. These mechanisms play a crucial role in shaping phenotypic diversity in humans. High-throughput technologies, such as expression microarrays and next-generation sequencing (NGS), have enabled precise analysis of transcripts for thousands of genes genome-wide. These methods have enabled researchers to measure gene expression levels in various tissues and cells and to gain deeper insights into previously inaccessible biological processes. Numerous studies show that gene expression varies significantly among individuals. However, there are also notable differences between populations from different continental groups, driven by genetic, epigenetic, environmental factors, and natural selection. Furthermore, disease states represent an important factor influencing gene activity, as they can significantly alter the transcriptomic profiles of individual cells. In this context, comparative population genetic studies help uncover the molecular mechanisms underlying complex phenotypic traits and identify population-specific features of transcriptomic profiles in both health and disease. However, despite significant progress in this field, many aspects remain underexplored. Specifically, the distribution of gene expression variability among populations, the degree of research coverage for specific ethnic groups, the spectrum of biological materials used, and the contribution of population affiliation to observed differences in gene expression during pathological conditions require further investigation. This review presents an overview of contemporary research focused on analyzing variability in expression profiles across different human populations. It summarizes findings from individual studies, outlines the advantages and limitations of the methods employed, highlights key research directions in population transcriptomics, and discusses potential practical applications of the data obtained.

   Data on mitochondrial DNA (mtDNA) polymorphism at the population level are of significant interest to researchers in the fields of population and ethnic genetics, forensic medicine, and forensic science. In the present study, we have obtained data on the variability of whole mitochondrial genomes in the immigrant East Slavic population of Northeastern Siberia (using the Magadan region as an example). The study yielded novel data concerning mtDNA variability in the Magadan region’s inhabitants comprising maternal lineages of Russians (N = 49) and Ukrainians (N = 15), as well as individuals with a mixture of maternal and paternal ancestries, including Russians on the maternal side and indigenous populations (Koryaks, Evenes, and Itelmens) on the paternal side (N = 4). In addition, the mitogenomes of the Russian population from the Novgorod, Kaluga, and Yaroslavl regions (N = 15) were sequenced to enhance the power of the phylogeographic analysis. The results of the study demonstrated that the mitochondrial gene pool of the East Slavic immigrant population in the Magadan region is characterized by a high level of diversity. The analysis of genetic differentiation of Russian populations within Russia, as measured by the variability of complete mitochondrial genomes, revealed a low level of interpopulation differences (Fst = 0.15 %, P = 0.2). The results of multidimensional scaling of Fst distances indicate that the Russians residing in the Magadan region are genetically similar to the Russian populations inhabiting the southwestern part of the country, specifically the Belgorod and Orel regions. The gene pool of the Russian population in the Magadan region is predominantly characterized by mtDNA haplotypes of West Eurasian (including European) origin. The prevalence of East Asian-derived haplotypes among the Russian population is relatively low, accounting for approximately 4.8 % of the total. However, certain East Asian-specific haplogroups, such as F1b1 and Z1a1a, have demonstrated a prolonged presence in the gene pools of Eastern European populations, as evidenced by phylogeographic analysis. Among the European mtDNA haplotypes of Russians from the Magadan region, Eastern European variants predominate, and they also have a high proportion of mtDNA haplotypes specific to Slavs (19.4 %). Furthermore, rare mtDNA haplotypes have been identified in the mitochondrial gene pools of Russians and Ukrainians residing in the Magadan region. These rare haplotypes are linked to the maternal lines of Empress Alexandra Fedorovna Romanova (haplogroup H1af2) and Prince Dmitry, son of Prince Alexander Nevsky (haplogroup F1b1-a3a2a).

   The Forest and Tundra Nenets in different areas of the Yamalo-Nenets Autonomous Okrug were studied using Y-chromosome markers. The results of analyzing the genetic structure of Nenets clans using 44 STR markers of the Y chromosome are presented, taking into account their presence in subethnoses (Tundra and Forest Nenets), as well as to the Kharyuchi (“true Nenets”) and Vanuito (“foreigners”) phratries. The number of the Nenets (N = 606) includes the Tundra (N = 536) and Forest (N = 70) Nenets. Sublineage N1a2b1b1a~-B170 is specific for the clans in the Kharyuchi phratry, and sublineage N1a2b1b1b-B172, for the clans in the Vanuito phratry. Most Forest Nenets clans have haplogroup N1a2b1-B478. All males of the Pyak clan, which is prevalent in the Forest Nenets, have a specific haplogroup, N1a1a1a1a2a1c1~. The results of the study suggest that the Nenets clan associations typically have a common ancestor in the male line and are characterized by a recent founder effect. Each Nenets clan has its own specific cluster of haplotypes, equidistant from each other. The structure of Y-chromosome haplotypes and haplogroups in the Nenets gene pool includes the Nenets heritage from the Khanty and Enets. Many samples from these sample sets were shown to have rare haplotypes that were absent from the baseline data and to differ significantly from the other haplotypes found in the populations. They belong to various rare branches of the Y-chromosome haplogroups found only in these sample sets. Some samples form haplotype variants that have not been described previously and allow us to characterize the phylogeny of these lineages in more detail. The Forest and Tundra Nenets differ greatly in the composition of haplogroups, which is fully consistent with ethnological and linguistic data on the origin of these populations. The predominant haplogroups are N1a1a1a1a2a1c1~-Y13850, Y13852, Y28540 CTS9108 (xY24219, Y24375) and N1a2b1-B478, Z35080, Z35081, Z35082, Z35083, Z35084 (xB169) in the Forest Nenets, and N1a2b1b1a~-B170 (xZ35104), N1a1a1a1a2a1c~-Y13850, Y13852, Y13138, PH3340 (xY24219, Y24365) and N1a2b1b1b-B172, Z35108 in the Tundra Nenets.

   Occupying a fairly extensive territory within the East European Plain, representatives of the Chernyakhov culture interacted with many synchronous tribes of other cultures inhabiting neighbouring regions. The question of a possible Proto-Slavic component in the population of the Chernyakhov culture is a subject of many years of discussion, but there is still no evidence for the genetic contribution of representatives of this culture to the gene pool of the Slavs in the subsequent historical period. In this study, we present the results of the craniological and genetic analysis of an individual from the Krynichki burial ground, presumably belonging to the Slavic part of the population of the Chernyakhov culture. A craniometric comparative analysis was conducted for several series of skulls of the East Slavs and representatives of the Chernyakhov culture. The comparison of intragroup variability in the groups of the two cultures showed marked differences between them in the first three principal components. At the same time, the East Slavic and Chernyakhov cultures have similar levels of craniological variability. Differences between female specimens are not so pronounced as those of males’. Based on the analysis of whole-genome sequencing data, the individual from the Krynichki was identified as being a female. The complete sequence of mitochondrial DNA, which belongs to the haplogroup H5a1a1, was reconstructed. For this mitochondrial lineage, a phylogenetic relationship
was revealed with eight specimens from publicly available genomic databases, five of which belong to representatives of the present-day West and East Slavic populations. Furthermore, we revealed a mitochondrial sequence identical to that from our previous research on an individual from a medieval burial site located in the modern Vologda region, which is thought to have Slavic ancestry. The complete match between the medieval individual’s mtDNA sequence and that of a representative of the Chernyakhov culture points to their likely maternal ancestry. Thus, a possible continuity between representatives of the Chernyakhov culture (3^rd century AD) and the population of Ancient Rus’ (the second half of the 12^th–early 13^th centuries AD) has for the first time been shown, as genomic data suggest.