Vol 54, No 6 (2018)

Schizophrenia is a complex multifactorial disease, in most cases manifested as a result of the interaction of genetic and psychological factors, as well as certain environmental conditions. However, genetic factors certainly play a determining role in the predisposition to schizophrenia. The coefficient of heritability of schizophrenia is about 80%, which is typical of the most highly inherited multifactorial diseases. This review presents the results of the latest world studies of genetic factors in the development of schizophrenia, including epigenetic, genome-wide association studies, and next generation sequencing.

The sbr gene is an ortholog of evolutionarily conservative nxf1 (nuclear export factor) genes that control nuclear-cytoplasmic transport of mRNA in various eukaryotic organisms. Mutations of sbr exhibit a broad range of pleiotropic effects, which are characteristic of “housekeeping” genes. Certain allele-specific manifestations of the sbr gene in neurogenesis and behavior facilitate a deeper understanding of not only universal but also highly specialized functions of this gene. Among such characteristic features of adult males with an sbr¹² mutation are reduced locomotor activity as revealed in the negative geotaxis test and significant morphological disruptions of the ellipsoid body and the medulla, both of which are important for locomotion. The character of defects in the ellipsoid body and the medulla suggests that the SBR protein is essential for the normal formation and functioning of these nerve centers, and that the protein carries not only universal but also specialized functions.

Cold temperature is an important environmental factor that affects the lives of many organisms in various ways. In this study, cold temperature was found to promote the release of zoospores from Phytophthora sojae sporangia. To better understand this phenomenon, Illumina sequencing was used to examine the differential expression of P. sojae genes between three control libraries and three cold temperature (4°C) treatment libraries. The six libraries generated 1.04, 1.17, 1.11, 0.96, 1.23, and 1.13 million clean sequencing reads. Comparison of the gene expression levels between the control and cold treatment conditions revealed 175 differentially expressed genes (DEGs), including 38 up-regulated and 137 down-regulated genes in the cold temperature group compared to the control group. The DEGs were functionally classified using the Clusters of Orthologous Groups (COG) database, and the results indicated that these DEGs were mainly involved in signal transduction, translation, ribosomal structure and biogenesis, transcription and carbohydrate transport and metabolism. KEGG pathway analysis showed that the top 20 pathways significantly enriched in DEGs included amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, and starch and sucrose metabolism. Some of the DEGs are involved in the release of zoospores from P. sojae sporangia is discussed in the present work. This information will be helpful for understanding the mechanism of zoospore release induced by cold temperature.

Cytogenetic analysis was conducted on a set of 67 Ethiopian wheat accessions collected by the expedition of N.I. Vavilov in 1927 and 85 years later by the Joint Ethiopian–Russian Biological Expedition (JERBE) in 2012 in the same sites of Ethiopia. The preservation of the polymorphism system of heterochromatic chromosome sites upon the change in the Ethiopian wheat population structure over the past period owing to a frequency shift of some specific chromosome variants and an increase in the proportion of genotypes carrying marker rearrangements was demonstrated. The unevenness of the geographical distribution of the 2A:4B translocation and of the 5A inversion was identified, and it was demonstrated that wheat accessions from Eritrea were cytogenetically the most isolated from the population from the central regions of Ethiopia. A low level of the Ethiopian wheat polymorphism was found along with the prevalence of the same chromosome rearrangement variants, which was indicative of monophyletic origin of the species. It was suggested that Triticum aethiopicum could have diverged from Ethiopian emmer as a result of hybridization with other wheat species, while subsequent evolution of these species occurred independently. Evidence for the participation of Ethiopian wheat in the formation of the gene pool of the unique Moroccan group of T. dicoccum was obtained.

The first characterization of the genetic variability in populations of S. flavicollis on the eastern border of the range is presented. Seven individuals from the most northeastern habitat of the species (Middle Urals) were karotyped. No deviations from the standard chromosome set, either by the chromosome number or morphology, were revealed. Analysis of the mtDNA cytochrome b gene sequences (1133 bp) in 44 individuals from five populations on the eastern border of the species range (Middle and Southern Urals) resulted in identification of 17 haplotypes. All haplotypes were new and not found earlier in other parts of the species range. The genetic diversity indices and analysis of the demographic and genetic structure indicate a relatively recent origin of the populations under study as a result of rapid expansion. Phylogenetic analysis (97 haplotypes, including the GenBank data) showed that all haplotypes described at the eastern border of the range belonged to the same phylogroup distributed in the Balkan region, Northern and Eastern Europe, and Russia (Samara oblast). Close relationships between the examined populations and the populations from the northern part of the species range in Eastern Europe was demonstrated.

The population structure of Pacific cod Gadus macrocephalus in the southern part of the range and adjacent regions is studied on the basis of the results of microsatellite analyses. Collected data indicate heterogeneity of this species population within the studied area. According to the obtained F_ST values, Pacific cod from the waters of the Republic of Korea (Yellow Sea side) and northwestern part of the Sea of Okhotsk significantly differ from all other studied regions (Table 4). Significant differentiation was also revealed between samples from the waters of the Tatar Strait and all other regions except for South Kurils Pacific cod (both Sea of Okhotsk and Pacific Ocean sides). These two latter sample collections were similar to each other as well. A low level of differentiation was also shown for the Peter the Great Bay and the East Sea/Sea of Japan waters of the Republic of Korea.

Wood mice of the genus Apodemus belong to the most frequent and epidemiologically important rodents of Europe and adjacent regions. Previous studies showed that in the Middle East region species of this genus exhibit extraordinary morphological similarity precluding their proper determination without application of molecular characters. In order to determine the species of the studied populations and to obtain an insight into their phylogeographic history, we analyzed their genetic variation. We sequenced 1139 bp fragment of the mitochondrial DNA control region and flanking tRNA genes in samples collected from six localities. Phylogenetic analyses revealed presence of distinct clades corresponding to species A. uralensis and A. witherbyi. In most localities we confirmed presence of both species which suggests their large sympatric and syntopic occurrence. We recognized an extensive genetic variability, 38 specimens of A. uralensis belong to 32 distinct haplotypes, while 19 specimens of A. witherbyi to 14 haplotypes. We confirmed presence of several distinct haplotypes that may originate from multiple wood mouse colonization waves from distinct geographic regions.

The expression profile of the ZEB1, ZEB2, VIM, CDH1, SFRP2, FOXQ1, TNC, MACC1, PLS3, CFTR, FLNA, MUC2, TFF3, and RARRES3 genes, as well as the mutational status of the KRAS, NRAS, BRAF, and PIK3CA genes, were investigated in 40 patients with colorectal cancer and liver metastases. A comparative analysis of changes in gene expression in primary tumor cells and liver metastases was performed. Statistically significant differences were found between the expression levels of the ZEB2 (p = 0.004), VIM (p < 0.001), FLNA (p = 0.04), and MUC2 (p < 0.001) genes. It was demonstrated that the overall frequency of mutations of the KRAS gene was 18/40 (45%) and the PIK3CA gene was 9/40 (23%). Mutations in the NRAS and BRAF genes were not found. The concordance between the primary tumor and metastases in the liver by mutation status was 100%.

Hemophilia A is a recessive X-linked hereditary disease, so its manifestation in women is extremely rare and can be a result of an asymmetric X-chromosome inactivation or, even more rarely, of a presence of mutations in both FVIII gene alleles. We conducted a mutation screening of the FVIII gene in two female patients with clinical hemophilia A manifestation in this study. One patient had a hereditary disease; the second one was diagnosed with acquired hemophilia A as an adult. Both patients carried the same missense mutation His2026Arg. The patient with the hereditary form of the disease also had previously known microinsertion c.4379_4380 insA (p.Asn1460Lys-fs*1). We found no additional aberrations by sequencing of all functionally significant parts of the factor VIII gene of the patient with acquired hemophilia but showed clear asymmetric inactivation of X-chromosomes. Therefore, one of the possible explanations for the emergence of the hemophilic syndrome in this case can be the delayed manifestation of the FVIII gene germline mutation owing to the enhancement of hematopoiesis clonality with age.

Huntington disease (Huntington chorea, HD) is a severe neurodegenerative disease determined by polyglutamine. Polyglutamine expansion in exon 1 of the HTT gene causes Huntington disease. To date, less than 35 CAG triplets are suggested to be present in normal alleles. Alleles bearing from 27 to 35 CAG repeats are generally considered as intermediate or premutation. Alleles with the number of CAG repeats varying from 36 to 39 demonstrate reduced penetrance and result in late manifestation of the disease. To date, no studies based on representative samples of Russian residents estimating the frequencies of premutation and alleles with reduced penetrance have been published. Meanwhile, this is extremely important for genetic counseling of patients bearing such alleles and for the calculation of risks for their offspring. In the present study, the analysis of samples of Russian patients with incoming diagnoses of Huntington chorea (N = 1092), Wilson–Konovalov disease (N = 333), Hallervorden–Spatz disease (N = 33) and a control group consisting of 230 unexamined individuals from the Russian Federation under 45 years of age was carried out. A spectrum of CAG repeat length in the HTT gene in patients with HD was obtained. Patients with HD were detected in the samples of patients with incoming diagnoses of Wilson–Konovalov disease and Hallervorden–Spatz disease. This observation indicates the complexity of differential diagnosis of these diseases. An assumption was made that an allele with 36 CAG repeats should be classified as premutation. We confirmed the previously observed trend for the increased number of CAG repeats in the case of paternal transmission of the mutant allele. The frequency of premutation allele of 2.6% in Russian residents was established.

A developed method of multiplex genotyping of polymorphic markers of genes associated with cognitive abilities and neuropsychiatric diseases is based on multilocus PCR and MALDI-TOF mass spectrometry of DNA molecules. The frequencies of 32 single-nucleotide markers localized in 24 genes are analyzed in a sample of elderly people from the Russian population of Tomsk. The data obtained are compared with data for populations from the 1000 Genomes Project.

The plant transcription factor INNER NO OUTER (INO) plays a major role in development of the outer integument of bitegmic ovules. INO sequences of ten Capsicum species were identified. Levels of nucleotide and amino acid variability in Capsicum INO were determined, and 18 amino acid residue substitutions localized in the YABBY domain and in the interdomain region were revealed. The ZnF domain was invariant in all the analyzed Capsicum species. In the constructed dendrogram, all the Capsicum species form a single cluster in the INO clade, the basal branches to which are formed by the INO proteins of the Solanum and Nicotiana species.