НИИ
медицинской
генетики

The effects of the demographic history of mankind have led to the fact that the indigenous peoples of Dagestan and Siberia are inferior in terms of genetic diversity to the populations of Europe, which affects the level of identification informativeness of standard forensic autosomal markers in these populations. In our study, we evaluated the effectiveness of two standard sets of autosomal STRs (13 CODIS, 20 CODIS, Combined DNA Index System) for the genetic examination of parent–child relationship in four highly inbred populations of the Russian Federation and the Russian population, using two types of reference frequencies. The results of the study confirmed the assumption that the level of identification informativity of standard autosomal markers in highly inbred populations of Siberia and Dagestan is lower than in the Russian population. The total information content of markers of the new CODIS standard exceeds the threshold values required in the order of the Ministry of Health and Social Development of the Russian Federation (no. 346n). At the same time, the probability of a false positive result increases with an increase in the inbreeding coefficient in the population.

Неблагоприятное ремоделирование ЛЖ диагностировано у 19 больных (25,7%). Анализ генных ассоциаций показал статистически значимую связь rs1800629 TNFA ( χ2=4,748; p=0,029), rs5353 SELE ( χ2=10,85; p=0,004) и rs6632528 VEGFD ( χ2=8,127; p=0,017) с увеличением риска развития ИМпST. Выявлена более высокая концентрация IL-10 на 7 сут. ИМ (p=0,05) и через 6 мес. (p=0,028) у носителей генотипа A/T rs3024492 в гене IL10, а также FGF у носителей генотипа T/T rs13122694 в гене FGF2 к 6 мес. после индексного события (p=0,04). Обнаружена зависимость основных показателей ЛЖ от генотипов полиморфизма rs3024492 IL10, rs13122694 FGF2 и rs4830939 VGEFD. В 1 сут. ИМ у гетерозигот по rs3024492 IL10 контрактильная функция ЛЖ была хуже в сравнении с носителями генотипа T/T. Также носители генотипа T/T rs13122694 FGF2 отличались более высокими показателями фракции выброса ЛЖ, продольной глобальной деформации ЛЖ и меньшими значениями конечно-систолического индекса ЛЖ в раннем постинфарктном периоде. В отдаленном постинфарктном периоде носители генотипа T/T rs4830939 VEGFD отличались большей степенью дилатации ЛЖ, чем носители генотипов C/C и C/T. Таким образом, в настоящем исследовании показан вклад полиморфизма генов системы воспаления в формирование предрасположенности к ИМпSТ— как на уровне фенотипа в целом, так и на уровне формирования отдельных признаков.

The level of chromosomal abnormalities in the somatic cells of adult individuals is characterized by significant interindividual variability, which may be partly affected by the genetic and epigenetic background. The epigenetic landscape in cells is largely determined by genome methylation. This study aimed to analyze the relationships between global genome methylation and the frequencies of chromosome abnormalities in lymphocytes of plutonium workers. The frequencies of chromosome aberrations, micronuclei, aneuploidy of chromosomes 2, 7, 8, 12, X, and Y and sister chromatid exchanges were analyzed in the lymphocytes of 40 male workers from a nuclear chemical facility (Seversk, Russia) with incorporated plutonium-239 and 49 healthy male volunteers who had no occupational exposure to ionizing radiation. The long interspersed nuclear elements-1 (LINE-1) methylation index was assessed as a well-known marker of global genome methylation. The frequencies of centromere-negative micronuclei (4.74 ± 2.26 vs. 3.02 ± 1.69‰), chromosome-type aberrations (0.81 ± 0.79 vs. 0.44 ± 0.69%), and total chromosome non-disjunction (0.93 ± 0.43 vs. 0.50 ± 0.25%) were significantly higher in the group of workers than in controls (p < 0.05). The LINE-1 methylation index did not differ significantly between the worker and control groups (74.93 ± 3.63 vs. 73.92 ± 4.62%). Correlations between LINE-1 methylation and the frequency of micronuclei (R = –0.35, p = 0.031) were observed in the control group, whereas correlations of LINE-1 methylation with chromatid-type aberrations (R = –0.42, p = 0.012) (but not chromosome-type aberrations) and with sister chromatid exchanges (R = –0.53, p = 0.004) were observed only in the group of plutonium workers. Thus, LINE-1 hypomethylation after plutonium exposure is associated mainly with chromatid breaks, either repaired or misrepaired.

In humans, aneuploidy is incompatible with the birth of healthy children and mainly leads to the death of embryos in the early stages of development in the first trimester of pregnancy. Trisomy 16 is the most common aneuploidy among spontaneous abortions of the first trimester of pregnancy. However, the mechanisms leading to the death of embryos with trisomy 16 remain insufficiently investigated. One of these potential mechanisms is abnormal placental development, including aberrant remodeling of spiral arteries. Spiral artery remodeling involves the migration of trophoblast cells into the maternal spiral arteries, replacing their endothelium and remodeling to ensure a stable embryonic nutrition and oxygen supply. This is a complex process which depends on many factors from both the embryo and the mother. We analyzed the methylation level of seven genes (ADORA2B, NPR3, PRDM1, PSG2, PHTLH, SV2C, and TICAM2) involved in placental development in the chorionic villi of spontaneous abortions with trisomy 16 (n = 14), compared with spontaneous abortions with a normal karyotype (n = 31) and the control group of induced abortions (n = 10). To obtain sequencing libraries, targeted amplification of individual gene regions using designed oligonucleotide primers for bisulfite-converted DNA was used. The analysis was carried out using targeted bisulfite massive parallel sequencing. In the group of spontaneous abortions with trisomy 16, the level of methylation of the PRDM1 and PSG2 genes was significantly increased compared to induced abortions (p = 0.0004 and p = 0.0015, respectively). In the group of spontaneous abortions, there was no increase in the level of methylation of the PRDM1 and PSG2 genes, but the level of methylation of the ADORA2B gene was significantly increased compared to the induced abortions (p = 0.032). The results obtained indicate the potential mechanisms of the pathogenetic effect of trisomy 16 on the placental development with the participation of the studied genes.