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Overproduction of reactive oxygen species (ROS) and, as a result, uncontrolled oxidative stress (OS) can play a central role in disorders of fetal hemodynamics and subsequent development of adverse perinatal outcomes in newborns with fetal growth restriction (FGR). Given the epigenetic nature of such disorders, the aim of our study was to evaluate the expression of miRNAs associated with OS and endothelial dysfunction (miR-27a-3p, miR-30b-5p, miR-125b-5p, miR-221-3p, miR-451a and miR-574-3p) in umbilical cord blood using real-time quantitative RT-PCR. &Mu, iRNA expression was evaluated in patients with FGR delivery before (n = 9 pregnant) and after 34 weeks of gestation (n = 13 pregnant), and the control groups corresponding to the main groups by gestational age (13 pregnant women in each group, respectively). A significant increase in miR-451a expression was detected in late-onset FGR and correlations with fetoplacental and cerebral circulation were established (increase of resistance in the umbilical artery (pulsatility index, PI UA (umbilical artery): r = &minus, 0.59, p = 0.001) and a decrease in cerebral blood flow (CPR: r = 0.48, p = 0.009)). The change in miR-125b-5p expression in the placenta is associated with reduced Doppler of cerebral hemodynamics (CPR: r = 0.73, p = 0.003, PI MCA (middle cerebral artery) : r = 0.79, p = 0.0007), and newborn weight (r = 0.56, p = 0.04) in early-onset FGR. In addition, significant changes in miR-125b-5p and miR-451a expression in umbilical cord blood plasma were found in newborns with neonatal respiratory distress syndrome (NRDS) (in early-onset FGR) and very low birth weight (VLBW) (in late-onset FGR). A number of key signaling pathways have been identified in which the regulation of the studied miRNAs is involved, including angiogenesis, neurotrophin signaling pathway and oxidative stress response. In general, our study showed that changes of the redox homeostasis in the mother-placenta-fetus system in FGR and subsequent perinatal outcomes may be due to differential expression of oxidative stress-associated miRNAs.

Changes in the oxygen partial pressure caused by a violation of uteroplacental perfusion are considered a powerful inducer of a cascade of reactions leading to the clinical manifestation of preeclampsia (PE). At the same time, the induction of oxygen-dependent molecule expression, in particular, miRNA and erythropoietin, is modulated. Therefore, the focus of our study was aimed at estimating the miRNA expression profile of placental tissue and blood plasma in pregnant women with preeclampsia using deep sequencing and quantitative RT-PCR, as well as determining the concentration of erythropoietin. The expression of miR-27b-3p, miR-92b-3p, miR-125b-5p, miR-181a-5p, and miR-186-5p, as regulated by hypoxia/reoxygenation, was significantly increased in blood plasma during early-onset preeclampsia. The possibility of detecting early PE according to the logistic regression model (miR-92b-3p, miR-125b-5p, and miR-181a-5p (AUC = 0.91)) was evaluated. Furthermore, the erythropoietin level, which is regulated by miR-125b-5p, was significantly increased. According to PANTHER14.1, the participation of these miRNAs in the regulation of pathways, such as the hypoxia&rsquo, s response via HIF activation, oxidative stress response, angiogenesis, and the VEGF signaling pathway, were determined.

Human mitochondrial DNA haplogroup U is among the initial maternal founders in Southwest Asia and Europe and one that best indicates matrilineal genetic continuity between late Pleistocene hunter-gatherer groups and present-day populations of Europe. While most haplogroup U subclades are older than 30 thousand years, the comparatively recent coalescence time of the extant variation of haplogroup U7 (∼16-19 thousand years ago) suggests that its current distribution is the consequence of more recent dispersal events, despite its wide geographical range across Europe, the Near East and South Asia. Here we report 267 new U7 mitogenomes that - analysed alongside 100 published ones - enable us to discern at least two distinct temporal phases of dispersal, both of which most likely emanated from the Near East. The earlier one began prior to the Holocene (∼11.5 thousand years ago) towards South Asia, while the later dispersal took place more recently towards Mediterranean Europe during the Neolithic (∼8 thousand years ago). These findings imply that the carriers of haplogroup U7 spread to South Asia and Europe before the suggested Bronze Age expansion of Indo-European languages from the Pontic-Caspian Steppe region., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

We report the de novo occurrence of a heteroplasmic 12706T-->C (12705C) ND5 mutation associated with the clinical expression of fatal Leigh syndrome. Phylogenetic analysis of several cases having the 12706C mutation confirmed that this mutation occurred independently in distinctive mtDNA backgrounds. In each of these cases, the low level of heteroplasmy and the association of the mutation with a deleterious phenotype indicated that the 12706C had a primary role in the expression of LS/MELAS in its carriers. Secondary structure analysis of the ND5 protein further supported the deleterious role of the 12706C mutation, as it was found to affect a functionally significant transmembrane domain that is likely responsible for the proton-translocation function of complex I.

It has been often stated that the overall pattern of human maternal lineages in Europe is largely uniform. Yet this uniformity may also result from an insufficient depth and width of the phylogenetic analysis, in particular of the predominant western Eurasian haplogroup H that comprises nearly a half of the European mitochondrial DNA (mtDNA) pool. Making use of the coding sequence information from 267 mtDNA haplogroup (Hg) H sequences, we have analyzed 830 mtDNA genomes, from 11 European, Near and Middle Eastern, Central Asian and Altaian populations. In addition to the seven previously specified sub-haplogroups, we define fifteen novel sub-clades of Hg H present in the extant human populations of western Eurasia. The refinement of the phylogenetic resolution has allowed us to resolve a large number of homoplasies in phylogenetic trees of Hg H based on the first hypervariable segment (HVS-I) of mtDNA. As many as 50 out of 125 polymorphic positions in HVS-I were found to be mutated in more than one sub-cluster of Hg H. The phylogeographic analysis revealed that sub-Hgs H1(*), H1b, H1f, H2a, H3, H6a, H6b and H8 demonstrate distinct phylogeographic patterns. The monophyletic sub-haplogroups of Hg H provide means for further progress in the understanding of the (pre)historic movements of women in Eurasia and for the understanding of the present-day genetic diversity of western Eurasians in general.

The Saami are regarded as extreme genetic outliers among European populations. In this study, a high-resolution phylogenetic analysis of Saami genetic heritage was undertaken in a comprehensive context, through use of maternally inherited mitochondrial DNA (mtDNA) and paternally inherited Y-chromosomal variation. DNA variants present in the Saami were compared with those found in Europe and Siberia, through use of both new and previously published data from 445 Saami and 17, 096 western Eurasian and Siberian mtDNA samples, as well as 127 Saami and 2, 840 western Eurasian and Siberian Y-chromosome samples. It was shown that the "Saami motif" variant of mtDNA haplogroup U5b is present in a large area outside Scandinavia. A detailed phylogeographic analysis of one of the predominant Saami mtDNA haplogroups, U5b1b, which also includes the lineages of the "Saami motif, " was undertaken in 31 populations. The results indicate that the origin of U5b1b, as for the other predominant Saami haplogroup, V, is most likely in western, rather than eastern, Europe. Furthermore, an additional haplogroup (H1) spread among the Saami was virtually absent in 781 Samoyed and Ob-Ugric Siberians but was present in western and central European populations. The Y-chromosomal variety in the Saami is also consistent with their European ancestry. It suggests that the large genetic separation of the Saami from other Europeans is best explained by assuming that the Saami are descendants of a narrow, distinctive subset of Europeans. In particular, no evidence of a significant directional gene flow from extant aboriginal Siberian populations into the haploid gene pools of the Saami was found.

The frequencies of three alleles, CCR5delta32, CCR2-64I, and SDF1-3′A, known to decrease the risk of AIDS onset and the rate of the disease progression in HIV-infected individuals were determined in three native population samples from Russia, Ukraine, and Belarus. The frequencies of the alleles were 0.15, 0.12, 0.21; 0.12, 0.07, 0.20; and 0.12, 0.08, 0.26 for Russians, Ukrainians, and Belarussians, respectively. The proportion of the individuals without any of three protective alleles among Russians, Ukrainians, and Belarussians constituted 49, 65, and 61%, respectively. The genotype frequencies for the three loci studied were in Hardy–Weinberg equilibrium. Based on the three-locus genotype frequencies, the relative hazards of AIDS onset in HIV-infected individuals in each population were calculated as ranging from 0.79 to 0.88. In the samples of Eastern Slavs analyzed the estimated frequencies of the AIDS-protective alleles tested, as well as the frequencies of the corresponding genotypes and the relative hazards of AIDS onset were within the range of these parameters for the other European populations. The data on the allele frequencies and the relative hazard values in Russians, Ukrainians, and Belarussians can be used as the predictors of AIDS onset and progression rate in HIV-1-infected individuals from the populations studied.

Y chromosomes from representative sample of Eastern Ukrainians (94 individuals) were analyzed for composition and frequencies of haplogroups, defined by 11 biallelic loci located in non-recombining part of the chromosome (SRY1532, YAP, 92R7, DYF155S2, 12f2, Tat, M9, M17, M25,M89, andM56). In the Ukrainian gene, pool six haplogroups were revealed: E, F (including G and I), J, N3, P, and R1a1. These haplogroups were earlier detected in a study of Y-chromosome diversity on the territory of Europe as a whole. The major haplogroup in the Ukrainian gene pool, haplogroup R1a1 (earlier designated HG3), accounted for about 44% of all Y chromosomes in the sample examined. This haplogroup is thought to mark the migration patterns of the early Indo-Europeans and is associated with the distribution of the Kurgan archaeological culture. The second major haplogroup is haplogroup F (21.3%), which is a combination of the lineages differing by the time of appearance. Haplogroup P found with the frequency of 9.6%, represents the genetic contribution of the population originating from the ancient autochthonous population of Europe. Haplogroups J and E (11.7 and 4.2%, respectively) mark the migration patterns of the Middle-Eastern agriculturists during the Neolithic. The presence of the N3 lineage (9.6%) is likely explained by a contribution of the assimilated Finno–Ugric tribes. The data on the composition and frequencies of Y-chromosome haplogroups in the sample studied substantially supplement the existing picture of the male lineage distribution in the Eastern Slav population.