Exposure to ionizing radiation causes significant functional changes in human cells which lead to activation of various signaling pathways and transcriptional response of many genes. The magnitude of these changes is variable for different individuals, making the phenomenon of individual radiosensitivity. In the review, markers of individual radiosensitivity are described ranging from cytogenetic markers for assessing the efficiency of DNA repair of radiation-induced damage in cells to genome- and transcriptome-wide approaches to identify differentially expressed genes that determine various aspects of response to radiation exposure.

Mitochondrial genome, encoding respiratory chain subunits, is characterized by high polymorphism level in human populations. In most studies for susceptibility genes for common diseases, including cardiovascular diseases, the analysis is limited to the nuclear genome. It was shown that particular mtDNA genotypes may differ by oxidative phosphorylation efficiency. Some associations of mtDNA polymorphisms with cardiovascular diseases have been found. According to our results and published data, we suggest that mtDNA effect on cardiovascular system does not manifest in predisposition to cardiovascular diseases themselves but rather in risk of complications and comorbidities in the cardiovascular continuum.

We have held a replication associative study in case-control design of 30 SNPs of genes that showed association with cognitive functions or Alzheimer’s disease or schizophrenia according to the data of GWAS. A statistically significant association of the polymorphic variant rs12922317 of SNX29 gene with the Alzheimer’s disease in the Russian population was established, which was not found in other studies. Minor allele G rs12922317 of SNX29 gene was significantly more frequent among patients with the Alzheimer’s disease compared with control group (OR = 1.57, 95% CI 1.14-2.16, p = 0.006), and according to GWAS this marker was associated with schizophrenia.

Physiological changes in the brain with natural aging and the development of dementia have a common genetic basis, which makes it important to search for genetic variants that delineate the natural decline in cognitive abilities with age and dementia of the Alzheimer’s type. Objective: the search for the relationship between two polymorphic variants (rs429358 and rs7412) APOE gene and their protein isoforms (apoE) with the variability of cognitive functions in the elderly, determined by Montreal Cognitive Assessmnet (MoCA) total score. The study was performed on a group of 695 elderly people (177 men and 518 women) tested by a battery of MoCA tests. Genotyping was carried out by real-time PCR using TaqMan probes. The analysis of genotypic variability associations with the nominal trait was performed by the Kruskel-Wallis and the median test nonparametric methods.It was shown that the rs429358*C allele carriers and protein isoforms e4/e4+e2/e4+e3/e4 carriers in comparison with the e3/e3 homozygous have the greatest risk of decreased cognitive abilities in old age (OR (95% CI) was 1.51 (1.09 - 2.10), c² = 6.66, p = 0.01 and OR = 1.64, 95% CI (1.11 - 2.44), c² = 6.76, p = 0.009, respectively). Probably, the revealed associations indicate to the presence of common genes and mechanisms for dementia and intellect with normal variability of cognitive functions inheritance.

Tuberculosis is a significant medical and social problem due to the high prevalence, high degree of disability and mortality. Latent tuberculosis infection (LTBI) develops in the majority of cases after infection of M. tuberculosis . It is almost impossible to estimate exactly the prevalence LTBI (according to WHO - it is about 30% of population), because this condition diagnoses only in children and HIV-infected people. The aim of our study was to determine the genes associated with LTBI. 62 SNPs were analyzed in 70 LTBI patients and 445 healthy donors. Associations with LTBI were identified for three markers: rs2505675 (p_perm = 0.020), rs958617 (p_perm = 0.019), rs6676375 (p_perm = 0.021). Interlocus combinations of genotypes characterizing possible intergenic (epistatic) interactions were revealed for the risk assessment of LTBI by MB-MDR. Four two-locus statistically significant models (p <0.01) and 5 - three-locus models (p<0.001) were obtained including 14 SNPs. Detailed consideration of obtained models allowed for each inter locus combination to get from one to three combinations of genotypes predisposing to the development of LTBI, the OR values for which are from 1.97 to 15.66. Our results indicate that epistatic interactions might play an important role in LTBI.

Regulatory single nucleotide polymorphisms (rSNPs) are of substantial interest, because they play a significant role in the development of human pathology by altering the level of candidate genes expression. However they represent the least studied group of single nucleotide polymorphisms (SNPs). The purpose of this research was to study preeclampsia (PE) genetics components via the regulatory polymorphic variants of the new NDRG1 candidate gene and to detect the role of natural selection in its formation. In this work, we analyzed four rSNPs. Three ethnic group have been studied (Yakut, Russian, Buryat). We have detected significant associations of PE with three rSNPs NDRG1 gene: rs12678229, rs2227262 and rs3802252. We demonstrated the effect of weak negative selection for rs2227262. The results of this study provide evidence for a significant role of the new NDRG1 candidate gene in the variability of the placental tissue expression between normal pregnancy and PE.

Human populations live in different environmental conditions that require adaptation, especially to extreme environmental factors. The action of adaptive evolution is also reflected on human populations’ genetic constitution. The study highlights the variability analysis of 25 SNPs single nucleotide polymorphisms (SNP) related to adaptation to a cold climate, as well as influence of climatic and geographical factors on the genetic diversity of human populations. The growth of the genetic diversity among the studied markers from Africa according to a modern human’s displacement around the earth identified. Probably, the variability of alleles associated with adaptation to climate in some populations could be explained in the framework of the hypothesis of canalization/decanalization of genome-phenome relationships under natural selection during modern human dispersion.

Autosomal reciprocal translocations are among the most frequent chromosomal rearrangements in man. Though phenotypically normal, the carrier of reciprocal translocation may be at increased risk of having a chid with multiple malformations and mental retardation due to malsegregation at meiosis resulting in gametes with chromosome imbalance. An accurate estimate of the probability of this event is understandably desirable. Aim. The aim of this investigation was an analysis of prenatal selection, meiotic segregation and assessment of empirical risks for reciprocal translocation carriers of having a liveborn child with unbalanced karyotype on 49 reciprocal translocation carriers. Materials and Methods. The pachytene diagrams were analyzed for each translocation taking in account the exact lengths of the chromosomes involved. The observed and most probable unbalanced segments were evaluated using the Chromosome Imbalance Size-Viability Model and Surface of Viable Unbalances consisting of the measurement of chromosomal segments distal to the breakpoints expressed in percentage of haploid autosomal length - %HAL. Results. The tendency to preferential prenatal selection of zygotes is established due to the 2:2 alternate segregation. It is shown that the analysis of quantitative characteristics of quadrivalent and pachytene diagram allows to estimate the type of malsegregation producing the smallest imbalance and the risk of formation of unbalanced gametes. Evaluation of viability of zygotes may be an additional step in establishing of the recurrence risks. In 80% of cases the risk of a viable child with a chromosomal imbalance is regarded as low. Conclusions. Meiotic segregation of chromosomes in carriers of autosomal reciprocal translocations occurs with preferential formation and subsequent prenatal selection of zygotes due to alternate segregation. It is necessary to assess segregation giving the smallest imbalance and viability of the imbalance. Empirical risk was not found to be useful as a discriminating risk predictor in individual genetic counselling.

Introduction. Recurrent pregnancy losses is the loss of two or more consecutive pregnancies, it affects up to 5% of couples in the population. The average frequency of chromosomal abnormalities in human spontaneous abortions is about 50%, and if the chromosomal abnormalities are random events, the subsequent abortion should be cytogenetically normal in half of the cases, regardless of the karyotype of the previous miscarriage. The aim of this study was to determine is there a regular occurrence of the chromosome constitution in spontaneous abortions from the same woman. Materials and methods. A total of 108 cases of recurrent embryonic death in 51 families were studied. The karyotype of abortion was obtained using a combination of methods: standard cytogenetic analysis (73), CGH (29), FISH and aCGH (3 samples each). 35% (18/51) of women were healthy, 59% (30/51) had diseases associated with miscarriage. Results. The odds ratio (OR) of the loss of the second embryo with the same karyotype (normal or abnormal), as in the first abortion, was 6.98 (95% CI: 2.04-23.88, p = 0.0013). In 19 women from 51 (37%), all the dead embryos had normal karyotypes, and 7 of these women did not have a pathology that caused miscarriage. Among women with RM 35% (18/51) had both miscarriages with abnormal karyotypes. Of these, in 6 women, embryo anomalies were repeated trisomy of different chromosomes (heterotrisomies), in one family both abortions had trisomy 16. Eleven cases of repeated death of embryos proved to be a combination of different types of anomalies. The average age of women with two trisomic miscarriages was higher than in women with miscarriages with different types of anomalies (33.1 ± 3.45 and 28.7 ± 5.78 years, respectively, p = 0.025). Conclusions. The likelihood for subsequent abortion to be of the same karyotype (normal or abnormal), as the previous one, is increased. Repeated miscarriages with normal karyotypes may be due to the women’s etiological factors of miscarriage that were not diagnosed by standard survey methods. Some patients with recurrent trisomic abortions may have an increased risk of chromosomal nondisjunction than other women at the same age. The combination of abortions with different types of abnormalities from one woman is most likely random: it is unlikely that the presence of a specific type of anomaly could be associated with an increased risk of another type of anomaly, because different mechanisms are involved in their formation.