Vol 54, No 9 (2018)

The PAX6 gene encodes one of the key embryonic transcription factors and serves as a master regulator of eye and central nervous system morphogenesis in all species of bilaterian animals. The PAX6 protein contains two DNA binding domains: paired and homeobox. To ensure specific regulation of target genes, the domains are able to bind different DNA motifs either independently or in cooperation or even antagonizing in different cell contexts. PAX6 has a complex temporal and tissue-specific expression pattern. Abnormal levels of its expression, either excessive or insufficient, as well as a misbalanced ratio of expressed transcript variants, lead to the disturbance of embryogenesis. Compound heterozygous mutations in the PAX6 gene are lethal. Most heterozygous mutations lead to the loss of function of mutated PAX6 allele (haploinsufficiency). PAX6 function deficiency results in several phenotypes. The most frequent one is congenital aniridia (>90%), which is characterized by damage to various eye structures often accompanied by morphological and functional disorders of other organs and systems. The reasons for the varying expressiveness of mutant alleles of the PAX6 gene and the development of various phenotypes are still poorly understood. This review deals with the analysis of the current state of knowledge about the normal structure and functions of the PAX6 gene and its encoded protein, as well as the phenotypes associated with various mutations of this gene in humans.

Since last few decades hepatitis C virus (HCV) has been a major cause of death due to the involvement of acute and chronic type of liver diseases throughout the world. Genotype variability and mutations occurring at different regions of HCV genome provides a critical parameter for the study of sustained virological response (SVR) against mono and combinational therapies. Most of these mutations occurring in E2 and NS5A-ISDR regions in HCV genotypes play a significant role in SVR against Interferon-monotherapy and combination therapy. Therefore, the aim of the present study is to evaluate the SVR in various genotypes and the role of mutations in specific regions. In line with this, the NS5A and E2 proteins of HCV genotype 1 were found to suppress the double-stranded (ds) RNA-dependent protein kinase (PKR), which in turn is entailed in the cellular antiviral response stimulated by interferon (IFN). The response to IFN therapy varies between genotypes, with response rates among patients infected with types 2 and 3 nearly two-three-fold greater than in patients infected with type 1. Surprisingly, a considerable percentage of HCV genotype 3a infected patients do not react to treatment at all. In Japan, a link was observed between the numbers of mutations in an “interferon sensitivity determining region” (ISDR) and the result of interferon treatment in genotype 1b infected patients. Therefore, we published data on E2 (PePHD) and NS5A-ISDR regions including our data on SVR of different HCV genotypes, the relationship between the number and patterns of mutations in the E2 (PePHD) and NS5A-ISDR regions and responsiveness to IFN therapy.

The genus Elymus L. is a complicated aggregate of ecological and geographical races, species, subspecies, varieties, and hybrids. We suggest that comparative analysis of intragenomic polymorphism of internal transcribed spacers ITS1 and ITS2 of 35S rRNA genes in the supposed hybrids and their possible “parents” can be one of the approaches to verification of hybrid origin of the samples collected in nature to confirm or reject the hypotheses about their possible “parents.” Polymorphic sites (PS) in ITS of 23 Elymus species, as well as in two supposed interspecific Elymus hybrids and in a supposed intergeneric hybrid between Elymus × Hordeum determined as × Elyhordeum sp., were analyzed in the work. We collected all hybrids in the Altai. There were 2 and 5 PS in two samples of E. dahuricus and 1 and 4 PS in two studied samples of E. schrenkianus in the ITS1-5.8S rDNA-ITS2 region. From 0 to 4 (modes 0 and 3) PS were detected in 32 samples relating to 21 tetraploid Elymus species. More PS (14) were found in the × Elyhordeum sp. sample. A large number of single nucleotide substitutions were found in 5.8S rRNA in × Elyhordeum. It was shown that about half of them do not change the secondary structure of the 5.8S rRNA molecule, so these molecules probably retain the ability to work as a component of large subunit of a ribosome. On the other hand, the absence or weakening of 5.8S rDNA homogenization in × Elyhordeum indirectly suggests that a significant part of 5.8S rDNA is not transcribed. Paradoxically, ITS sequences of × Elyhordeum sp. are less polymorphic than 5.8S rDNA. There are no ITS sequences derived from Hordeum among × Elyhordeum ITS sequenced by Sanger method. No traces of the H subgenome and a subgenome originating from Agropyron (P-subgenome) are seen in the Alt 10–278 plant genome (a chimera, combining the morphological traits of Elymus, Elytrigia, and Agropyron). In this plant, as well as in the supposed intersectional hybrid Alt 11–60 distinguished by a mosaic of the traits typical for the E. caninus × E. mutabilis species, only 4 and 5 PS, respectively, are detected when sequencing by Sanger method. The comparison of ITS sequences of the supposed Elymus Alt 10–278 hybrid and its probable “parents” demonstrates that one of the species of the Elymus macrourus kinship circle, as well as the Elytrigia geniculata, could be one of its ancestors. The comparison of the ITS sequence of the supposed parental species with ITS of Alt 11–60 samples and five PS of the supposed Alt 11–60 hybrid does not contradict the hypothesis that this is an intersectional hybrid of the first generation that emerged with the involvement of E. caninus and E. mutabilis common in the Altai.

On the basis of directed chromosome substitution, ditelosomic (DT) wheat–barley substitution lines (2n = 42 = 40 + 2t) with participation of wild tetraploid barley Hordeum marinum ssp. gussoneanum Hudson (2n = 28) were first obtained and analyzed. GISH analysis of the substitution lines showed that they carried a pair of telocentric barley chromosomes. With the help of ditelosomic analysis, the lines were identified as DT7H^IL^mar(7A) and DT7H^IL^mar(7B). On the basis of the compensation test and the study of meiotic stability of substitution lines, it was demonstrated that 7H^IL^mar chromosome of H. marinum was homoeologous to the group 7 chromosomes of common wheat. Analysis of the gamete transfer frequency in the progeny of reciprocal hybrids between F₁ 7A-7H^IL^mar, 7B-7H^IL^mar, 7D-7H^IL^mar and Saratovskaya 29 cultivar showed that the gamete with alien chromosome n = 20 + t successfully competed with euploid gamete n = 21 in both macrosporogenesis and microsporogenesis.

Amphipods of the species Gmelinoides fasciatus are one of the dominant species in the littoral zone community of Lake Baikal. Earlier, on the basis of the analysis of the mitochondrial COX1 gene, four isolated populations within the species range were identified, between which there were no distinct geographical barriers. In the present study, a phylogenetic reconstruction of the evolutionary history of G. fasciatus with the molecular clock hypothesis is carried out. The population divergence time is dated back to the onset of global climate changes on the Pleistocene–Pliocene boundary at 1.8–2.3 Ma. As a result, the estimated substitution rate in the COX1 gene for G. fasciatus was 1.2–2.4% of substitutions per Myr, which corresponded to the values determined for other groups of invertebrates. It was demonstrated that geographical barriers that formed the populations of G. fasciatus periodically appeared and disappeared in the past, resulting from climate changes associated with the periods of global cooling and warming.

Data on the morphology, biology, and genetics of two ecological forms of pidschian-like whitefishes of the genus Coregonus, corresponding to the descriptions of East Siberian whitefish, C. lavaretus pidschian natio brachymystax, and glacial-plain whitefish, C. lavaretus pidschian natio glacialis, from the Anabar River of western Sakha (Yakutia) Republic (Russia), are presented. According to meristic characters, no differences are found between these ecological forms, while on the basis of plastic traits and occupied ecological niches these whitefishes differ substantially. We demonstrate that, on the basis of the sequences of the ND1 gene of the mtDNA, the East Siberian whitefishes are only slightly different from the whitefishes from the lower Ob River and Lake Teletskoye (Upper the Ob River basin), and probably have a common origin with them. Glacial-plain whitefishes from the Anabar River have a common origin with whitefishes from the water bodies of the Taimyr Peninsula and represent a complex of forms/species.

Specificity of the structure of gene pools of different ethno-territorial groups of the human population can underlie the epidemiological features of the spread of tuberculosis (TB) and the structure of the genetic component of the susceptibility to the disease. The variability of 62 genetic variants potentially associated with the risk of the development of TB in the Russian population of the city of Tomsk has been studied and the differentiation of various ethno-territorial groups of the world by these markers has been assessed. The studied sample comprised 445 Russian residents of the city of Tomsk without bronchopulmonary pathology. For comparison, the data on the variability of the genetic markers of interest in 26 populations from the 1000 Genomes Project was involved. In the Tomsk population, only the ancestral allele was found for seven of the 58 SNPs studied; the allele frequencies for 36 markers were within the limits of the values seen in other European populations; for 12 SNPs, the observed frequencies were closer to populations with a significant Mongoloid component. By the total of the SNPs, the Tomsk population, despite the geographical distance from the rest of the European populations, did not differ from them (in genetic distances and G_st statistics), although it had some features of the gene pool. Intergroup differentiation of the world populations by these SNPs reflects mainly interracial differences. The greatest differences in the genetic structure between the studied populations were seen for the markers localized in intergenic regions. Statistically significant differences were found when comparing the levels of the average expected heterozygosity between groups of “L4 carrier populations” of mycobacteria and “non-L4” populations, which indicates the impact of the prevalence of different pathogenic lineages of M. tuberculosis on the formation of population specificity of the allelic frequencies.

A great amount of attention has been paid to the study of the microbiota–gut–brain axis in recent years. Gut microbiota can affect development and functioning of the brain through synthesis of various neuroactive metabolites, such as neurotransmitters, hormones, and other compounds. In the present study, the presence and distribution are analyzed for the genes controlling the synthesis of enzymes involved in production of neuroactive compounds in 147 gut metagenomes of healthy people from Human Microbiome Project database and synthetic metagenome artificially assembled from 508 bacterial genomes. The analysis is conducted using the collected catalog of orthologs for 17 key enzymes and an algorithm developed for their search. As a result of analyses of genomic and metagenomic data of healthy people, seven bacterial genera containing the greatest number of enzyme genes and 8 enzymes out of 17 that are observed the most frequently are chosen. It is assumed that the selected “core” genera and enzymes form a metagenomic signature reflecting the neurometabolic potential of the human intestinal microbiota in the norm.

Single trophoblast cells circulating in the bloodstream of pregnant women are potential objects for noninvasive prenatal diagnosis. Owing to the very low concentration of cells of a fetal nature in the peripheral maternal blood, the choice of the method for whole genome amplification of the genetic material becomes topical. The key point in the use of single cells of a fetal nature for noninvasive prenatal diagnosis is to obtain DNA in an amount and of a quality acceptable for the analysis. In order to select the optimal method for whole genome amplification, a model experiment was conducted. We compared three different methods of whole genome amplification: linker-adaptor polymerase chain reaction (LA-PCR), degenerate oligonucleotide- primed PCR (DOP-PCR), and multiple displacement amplification (MDA). Subsequent analysis of the amplification products was performed by metaphase comparative genomic hybridization in order to evaluate the molecular karyotype of cells of a fetal nature with the known chromosome complement. As a result, an optimal method for whole genome amplification of the genetic material of single cells in a model experiment was determined by linker-adaptor PCR, which showed a more uniform representation of the genome regions compared with the other methods used.

To describe the population-genetic structure of the Russian population of Karachay-Cherkessia, the database of Compulsory Medical Insurance and marriage records for 1990–2000 were used. The Russian population is characterized by a low birth rate, low endogamy, low inbreeding, and a high level of miscegenation.