Today, mental disorders are one of the most important challenges for modern medicine. Despite the fact that mental illnesses do not significantly contribute to the mortality of the population, they have an important impact on the quality of life of each individual patient, as well as on public health and the economy of the country. According to statistical studies, about 40% of the Russian population has symptoms of mental disorders, and 5% need treatment.  As psychiatric genomics develops, disease risk prediction models based on biological structures continue to develop. Advances in the accessibility and complexity of big data, deep phenotyping, mapping of developmental trajectories, and the inclusion of large amounts of data on a large number of individuals will contribute to understanding the factors that ultimately play an important role in determining mental health. Polygenic and polyepigenetic indicators themselves, like any other marker, have a limited ability to predict the condition for which they were generated. It should be noted, however, that the optimal selection of genetic variants and other genomic markers, as well as the aggregation of related weights, are active areas of research. Continuous improvement of the technology (increasing the sample size of GWAS and the inclusion of different pedigrees, higher genotyping resolution, etc.) entails a constant revision of the guidelines for their calculation and interpretation. Due to the recent emergence of several methods discussed in this review, there is still insufficient evidence of their clinical usefulness, but as the technologies underlying functional genomics approaches continue to improve, further research is needed to assess clinical usefulness in psychiatry. It can be assumed that some of the methods described here will be replaced by newer approaches. However, the main idea is to include functional aspects rather than being guided solely by data-driven approaches.

Heterotaxy syndrome is usually accompanied by congenital heart defects, which predominantly determine the severity of the patient’s condition and the high mortality rate, reaching up to 80% in the first year of life. In some cases, heterotaxy is caused by chromosomal and genetic abnormalities, which have been actively studied in recent decades. According to literature data, the prevalence of pathogenic copy number variations (pCNVs) in this anomaly is estimated at 15-20%, while monogenic variants account for 10-20%. The aim of this study is to analyze the work of the past 10 years, which includes the results of genetic studies on patients with laterality disorders, and to summarize the findings to identify the most promising diagnostic methods. An electronic search was conducted using the PubMed and E-library databases, where techniques such as karyotyping, CNV determination, and exon sequencing were applied. In total, out of 1357 patients with heterotaxy who were examined by various methods in the reviewed studies, a suspected genetic cause was identified in 278 individuals, accounting for 20.5%. Karyotyping among 56 patients did not reveal any cases of aneuploidy. The search for pCNVs was conducted on 154 individuals, predominantly using array comparative genomic hybridization (aCGH), which resulted in the detection of aneuploidies in 4.5% of the subjects and pathogenic microstructural chromosomal rearrangements in 6.5%. Exome sequencing was performed on 1147 patients with heterotaxy, and pathogenic or likely pathogenic genetic variants were identified in 22.8% of cases. aCGH is considered a preferred diagnostic method due to the more severe clinical presentation of heterotaxy syndrome, which is often associated with microstructural chromosomal abnormalities, and its potential application in the prenatal stage. Exome sequencing is recommended as a second step for assessing the risk of heterotaxy recurrence in future pregnancies.

The use of genetic polymorphisms in determining the pathogenesis of the disease increases the effectiveness of early diagnosis and preventive measures of severe form of coronavirus. COVID-19 and its complications with pneumonia are a potential risk factor for pregnant women and can have negative consequences for both the mother and the fetus. Currently, special attention is paid to the study of the role of genetic factors in the outbreak of the coronavirus. The aim of the study: to determine the role of the ACE  gene Alu-element I/D polymorphism in the pathogenesis of COVID-19. According to the results of molecular-genetic examination and statistical analysis, alleles and genotypes of ACE  gene I/D polymorphism in pregnant women infected with coronavirus did not have significant differences compared to the control group (p=0.05). Conclusion: It is impossible to use this locus of the  ACE  gene to predict COVID-19 and its complications.

Background.  Next generation sequencing (NGS) has achieved unprecedented development in recent years. The Sanger sequencing method is actively used to validate variants identified using NGS. The use of the Sanger method is necessary when the identified variant is localized in a gene that has several pseudogenes. The presence of pseudogenes complicates the detection of pathogenic variants in protein-coding regions. The  PMS2 gene, associated with Lynch syndrome, has a large number of pseudogenes  PMS2P1-PMS2P14 and PMS2CL, so additional methodological approaches are required to verify the identified pathogenic variants.

Aim. Testing a validation protocol for identified  PMS2 gene pathogenic variants, taking into consideration the presence of numerous pseudogenes, which exhibit a high percentage of homology with the regions where the validated variants are found.

Methods. The article presents two cases with identified PMS2 gene pathogenic germline variants: chr7:5982823C>T (rs267608172) and chr7:6003716del (hg38).

Results. We developed an algorithm using nested PCR primers to validate the chr7:5982823C>T variant ( PMS2 gene, exon 12) identified by whole-genome sequencing. In the first round, a long fragment containing exons 9-12 is amplified; in the second round, a target fragment suitable for Sanger sequencing is amplified. To validate the chr7:6003716del variant (PMS2 gene, exon 4), the primers were selected in a special way: the differences in the nucleotide sequence of the gene and the pseudogene were located at the 3’-end of the forward primer. As a result, further Sanger sequencing uses the target fragment without pseudogene contamination.

Conclusions.  Specialized algorithms for Sanger sequencing of the PMS2 gene are necessary to ensure that highly homologous pseudogene sequences do not interfere with reading the functional gene sequence.

Y-autosome translocations are rare structural chromosomal abnormalities that have a different effect on the reproductive system, gametogenesis and human fertility. The article presents the results of genetic and semen examination of a group of 14 men with Y-autosomal translocations. Cytogenetic, molecular cytogenetic, molecular cytogenetic (FISH), molecular genetic and complex semen studies, including standard semen analysis and quantitative karyological analysis of immature germ cells (QKA of IGCs) from the ejaculate sediment, were performed. Non-mosaic (10 balanced and 4 unbalanced) translocations involving the Y chromosome and one of the autosomes (chromosomes 1, 5, 8, 13-16, 20-22) were detected. The patients were phenotypically normal men, without disorders of sex development, congenital malformations, growth and physical development disorders, mental retardation. Molecular analysis of the Y chromosome performed in 13 patients has detected the SRY locus in all patients; pathogenic Yq11 microdeletions (AZFa+b+c, AZFb+c) were found in two patients. Semen analysis shown various diagnosis, including azoospermia (n=11), severe oligozoospermia (n=1), oligoastenozoospermia (n=1), and normozoospermia (n=1). Signs of a complete or partial фдarrest at prophase I of meiosis were detected in 3 out of 7 patients who underwent QKA of IGCs.

The combination of an inverted duplication with a terminal 8p deletion (invdupdel(8p)) is a rare chromosomal rearrangement that manifests with neurodevelopmental delay, intellectual disability, heart defects, and brain abnormalities. It is known that a polymorphic paracentric inversion in the structure of mother’s chromosome 8 can lead to invdupdel(8p) in her child. We have created a system of DNA-probes to search with the FISH-method for cryptic inversion in chromosome 8 of the mother of a patient with developmental delay, muscle hypotonia, craniofacial anomalies and ring chromosome 8 caused by invdupdel(8p). An inversion in the structure of chromosome 8 in a woman was revealed, which indicates the need for prenatal diagnosis in the case of pregnancy.