Vol 55, No 9 (2019)

Multiple studies demonstrating the association of aggressive behavior with allelic variants of neurotransmitter system genes appear to be controversial, while “risk” alleles have no effect on impaired gene expression and functioning of encoded proteins. To explain these associations, we suggested the role of deregulated epigenetic processes caused by the changes in the spatial configuration of transcribed proteins owing to the impaired interaction with noncoding RNAs, which results in modified functioning of genetic networks. Stressful life events occurring during the pre- and postnatal period causing changes in DNA methylation and histone modifications, which disrupt expression of neurotransmitter genes with a long-lasting effect, represent the key factors causing the manifestation of aggressive behavior. The role of stressful life events in epigenome modifications is assumed to be caused by stress-sensitive transposable elements (TEs), whose processing results in the formation of noncoding RNAs probably affecting histone modifications and methylation of certain genomic loci. Transposable elements represent the key sources of sites of binding to transcription factors and regulate genome expression, while their ability to locus-specific transpositions under the stress and self-regulation by noncoding RNAs can explain both the long-term effect of behavioral impairments and their transgenerational transfer. Prevention of behavioral impairments and phenotypic manifestations of genetic liability to aggressive behavior requires the examination of the individual nature of epigenetic modifications for the further targeted action and their correction.

Using the method of massively parallel sequencing, differential miRNA expression profiles in the original and radioresistant variants of HeLa and DU145 cell lines after radiation exposure at the dose of 4 Gy were obtained. Comparative analysis made it possible to identify a group of miRNAs aberrant expression of which reflected the changes in cell metabolism of radioresistant variants that remained across a number of cell generations as compared to the original ones. The obtained results suggest that the role of miRNAs is associated with the maintenance of functional interaction between DNA methyltransferases, Myc transcription factor, and PTEN phosphatase in regulating the activity of PI3K/AKT and MAPK/ERK signaling pathways. This may underlie differences in realization of radioresistance of HeLa and DU145 cells.

This study examines the relationships and origin of a population of smelt (genus Hypomesus) that was recently found in the Barents Sea at a significant distance from the western boundary of its geographic range. Genetic analysis clearly identified this species as pond smelt H. olidus and showed its phylogenetic closeness and shared demographic history with H. olidus from the basin of the Bering Sea. Genetic differentiation indices suggest long isolation of populations of the Pacific and Barents Sea basins. The statistical estimates of historical demographic events, coupled with the paleographic data for the Arctic areas of Russia, show that certain populations of H. olidus might have survived in glacial refugia of the Polar Ural region. H. olidus might have passed repeatedly through a bottleneck in past glacial refugia, as well as in the recent time because of the harsh Arctic conditions.

An important problem of genetic counseling is to determine the personalized risk of the birth of a child with an unbalanced karyotype in families with reciprocal translocation carriers. The risks of the formation of zygotes with chromosomal imbalance among carriers of balanced autosomal translocations vary significantly. These risks will depend on the most probable type of malsegregation for each specific translocation, leading to the formation of unbalanced gametes, and the probable viability of zygotes, embryos, fetuses, or newborns with unbalanced karyotype. In turn, these probabilities depend on many factors, including cytogenetic and quantitative characteristics of the translocation. During regression analysis of several independent factors and characteristics affecting the segregation behavior of the quadrivalent in meiosis I from 49 autosomal reciprocal translocations, it was found that the terminal location of breakpoints on the chromosomes involved in the translocation is statistically significant, i.e., independently associated with the risk of the birth of a viable child with chromosomal imbalance.

The principal genetic demographic parameters that describe migration processes affecting the structure of the St. Petersburg population gene pool were determined on the basis of the demographic statistics obtained from the Petrostat Agency, All-Russian population censuses, and a sample survey of St. Petersburg residents. The migration coefficient was 0.36 according to the survey data, 0.42 according to the 2002 census, 0.44 according to the 2010 census, and 0.69 according to the 1897 census. The estimated average migration distance was 1746 km from the survey data, 1526 km according to the 2002 census, and 1652 km according to the 2010 census. The sources of the St. Petersburg population gene pool in different periods are discussed: in the 18th and 19th centuries, the main source was the population of the Upper Volga and Northwestern provinces of the Russian Empire, as well as foreign immigrants, whereas currently three quarters of the population gene pool originates from the Northwestern Federal District, 10% comes from natives of foreign countries, and only 6–9% is due to the population of the Central Federal District of the Russian Federation. An analysis of the Rosstat migration statistics showed that the composition of migrants by countries of exit varied over time. For instance, the share of migrants who arrived in St. Petersburg from Russia in the last five years ranged from 74 to 87%. In 2013–2014, most international migrants came from Uzbekistan (10% of all arrivals) and Tajikistan (3–4%), while in 2017, the countries with the highest number of migrants ranked as follows: Kyrgyzstan (almost 4%), Ukraine (about 2%), Belarus (1.5%), Kazakhstan (1.25%), and Armenia (1%). Migration processes determine the dynamics of the ethnic composition of the population. Gender differences in migration flows are manifested in different age structure and in unequal sex ratio within particular ethnic groups (e.g., predominance of men in the “young” ethnic diasporas: Armenians, Azerbaijani, and Uzbeks). The described features of migration processes in St. Petersburg should be taken into account when forming genetic marker databases for the purposes of DNA-based identification. The areas of migration attraction of St. Petersburg and Moscow overlap only partially, which predetermines the need to create separate databases for each megacity.

Atherosclerosis (AS) and AS-related pathologies such as coronary heart disease, myocardial infarction, angina pectoris, and stroke are the leading causes of death in the world. The atherogenesis can be influenced by many factors, in particular, overweight, hypertension, diabetes, hyperlipoproteinemia, and other diseases in anamnesis, as well as genetic predisposition, which may be due to single nucleotide polymorphisms (SNPs) in some cases. In this work, we studied only those regions of promoters of the human protein-coding genes where SNP markers of changes in the affinity of the TATA-binding protein (TBP) for these promoters have already been associated with the atherosclerosis-related pathologies. As a result, within the dbSNP database, we found those unannotated SNPs which change such affinity just as the known biomedical SNP markers do here (according to the predictions made by our Web service SNP_TATA_Z-tester, http://wwwmgs.bionet.nsc.ru/cgi-bin/mgs/tatascan_fox/start.pl). For example, the known SNP marker rs35036378 of the high risks of the primary pT1 tumor reduces the TBP affinity for the ESR2 gene promoter and, thus, the estrogen receptor β abundancy in blood, which is a known physiological marker of calcification of blood vessels in atherogenesis. Near this known SNP marker, we found an unannotated SNP rs766797386, which can also reduce the TBP affinity for the same promoter and, thus, decrease the abundance of the estrogen receptor β in blood. Thus, we propose rs766797386 as a candidate SNP marker for accelerated atherogenesis due to calcification of blood vessels. The possibility of using a diet of natural food with high abundance of calcium (Ca), which is recommended by nutritionists to slow down calcification in the case when individuals have SNP markers of accelerated calcification, is discussed in contrast to the use of Ca-enriched nutritional supplements that can cause the opposite effect. In the same way, a total of 33 candidate SNP markers were predicted and discussed to accelerate or slow down atherogenesis. After clinical verification, the candidate SNP markers predicted by this work can help those who would like to slow down atherogenesis through lifestyle corrections using their genome sequencing data.

The shaggy gene of Drosophila melanogaster encodes highly conserved serine-threonine protein kinase GSK3 (Glycogen Syntase Kinase 3), which plays an important role in different signaling pathways and metabolic processes. This study is the first to demonstrate that shaggy mutations affect lifespan, with an increase in longevity associated with a decrease in synapse activity. The results from this study on changes in shaggy expression in mutants suggest that the observed phenotypic changes are based on an alternation in the expression of minor shaggy transcripts induced by mutational changes in their regulatory region.