Vol 55, No 8 (2019)

Despite recent advances in genomics and the discovery of numerous genes involved in carcinogenesis, the mechanisms of malignant transformation of different tissues remain poorly understood in most cases. This review presents the current knowledge on the role of the MEN1 gene and its protein product menin in the development of multiple endocrine neoplasia type 1 (MEN1), or Wermer’s syndrome. Here, we discuss the putative molecular and genetic mechanisms of carcinogenesis associated with the MEN1 gene mutation, as well as available and promising in vivo and in vitro models for studying the molecular basis of the disease. The lack of clear data on the role of the MEN1 gene in tumor initiation and progression in patients with MEN1 syndrome allows us to suggest two models for occurrence of malignant transformation in endocrine tissues.

Owing to the changes in the general ecological situation in Russia, livestock losses from ovine anaplasmosis have rapidly increased in recent years. The development of a vaccine against this disease is therefore all the more relevant. A continuous culture of tick cells could be used as an appropriate substrate for producing biomass of the pathogen of ovine anaplasmosis, Anaplasma ovis, for the purpose of manufacturing a cell-cultural inactivated vaccine. Such a continuous cell line of the tick Dermacentor marginatus, the definitive reservoir host of A. ovis, has been obtained by cultivation of homogenized tick eggs on a modified Leibovitz medium L15. The established cell line DM-77 has an undifferentiated phenotype: the cells are rounded, with large nuclei and well-visible nucleoli. By the end of the study, the cell line was passaged eight times and did not express signs of growth rate decrease. The duplication time was 2.8 ± 0.3 days for cultivation in a medium with 10% fetal serum at 32°C.

The paper shows the possibility of experimental modification of the expression of imprinting in apomictic hybrids of maize with gamagrass through exposure to a synthetic nucleoside 5-azacytidine, which inhibits DNA methylation. In angiosperm plants with double fertilization, the ratio of maternal and paternal genomes in endosperm cells is usually 2F : 1M, respectively. Moreover, any deviations from it, most often lead to abortion of grains. Apomictic pseudogamous plants, in which seed fertilization requires the fertilization of the central cell, have developed various mechanisms to overcome the negative effect of imprinting associated with a deviation in the ratio of parental genomes in the endosperm from 2 : 1. However, in such an apomict as tetraploid gamagrass (Tripsacum dactyloides), owing to a significant deviation in the ratio of genomes in the endosperm, only about 25% of the seeds are viable and produce seedlings. The same picture is characteristic of its apomictic hybrids with corn. In this regard, we tried using 5-azacitidine to modify female imprinting and enhance the expression of genes, the dose of which is insufficient owing to the discrepancy between the number of paternal genomes and the required ratio. The results obtained suggest the possibility of modifying the expression of imprinting. At the same time, the effect of 5-azacytidine is found in both M₁ and the next three generations. In M₂, families are distinguished in which, compared to the control, not only the difference in averages but also the frequency nature of the experimental and control distributions on the basis of “grain weights” is reliable.

Necrotic genotypes of the aboriginal common wheat cultivars (Triticum aestivum L.) from Iran, Afghanistan, Palestine, and Transjordan were studied. It was shown that the cultivars carrying Ne1^w and Ne1^m alleles prevailed in all geographical regions, while the Ne1^s allele was found only in the Afghanistan cultivars. The occurrence of the Ne1^s allele may indicate that hexaploid common wheat emerged as a result of spontaneous hybridization between T. durum and Ae. squarrosa. The noncarriers (genotype ne1ne1ne2ne2) occupy virtually all the regions examined. They comprise 77.8% in Iran, 80.8% in Afghanistan, 92.9% in Palestine, and 80.0% in Transjordan. The carriers of the ne1ne1ne2ne2 genotype predominate among the spring cultivars of common wheat.

The aim of this study is an evaluation of the genetic diversity among nine emmer wheat [Triticum turgidum L. ssp. dicoccon (Schrank) Thell.] landrace populations, grown in Turkey by using simple sequence repeats (SSR) technique. Nine SSR primers produced 497 alleles, which ranged between 57 and 376 bp and they were 100% polymorphic. The mean number of allele per locus (n_a), the mean number of the effective allele (n_ea), the mean value of average genetic diversity (H_{e_avg.}), and the mean value of genetic diversity (H_e) were determined as 40.89, 13, 0.76, and 0.90 respectively. The genetic differentiation and the gene flow between populations calculated as 0.15 and 1.41 respectively. The A genome showed significantly higher estimates for H_{e_avg.} and n_a than the B genome according to Mann–Whitney U test analysis. Turkish emmer wheat landraces populations displayed considerably high genetic diversity. The SSR marker system determined efficiently the genetic diversity among the emmer wheat populations and it was successful to differentiate the landrace populations from each other. In situ and on-farm conservation strategies should be planned urgently in addition to the ex situ conservation programs for emmer wheat landraces as invaluable genetic resources.

In the present study, on the basis of cytogenetic and molecular genetic (mtDNA control region) analysis, genetic variability of the Muya valley vole, Alexandromys mujanensis, an endemic of Buryatia and the northwest of Zabaykalsky krai, was assessed. Three isolated valley vole populations from the Muisko-Kuandinskaya and Barguzinskaya depressions, as well as the Baunt Lake valley, were examined. Polymorphism in the number of autosomal arms (NFa = 46–49) with a stable number of chromosomes (2n = 38), determined by morphological variability of four pairs of autosomes (MMUJ2, MMUJ7, MMUJ8, and MMUJ14), rather than two, as previously thought, was revealed. To date, for the Muya valley vole, ten karyotype variants have been identified. It seems likely that chromosomal rearrangements (pericentric inversions, as well as two variants of fusion of acrocentric chromosome pairs, i.e., centromeric-centromeric and centromeric-telomeric), which led to variability in autosome morphology in the populations of the Muya valley vole, are not harmful. Analysis of the mtDNA control region revealed high haplotype and nucleotide diversity for the species as a whole, while in the valley vole samples from the Dzherginsky Nature Reserve (Barguzinskaya Depression) and the Baunt lake valley, nucleotide diversity was reduced compared to the sample from the Muisko-Kuandinskaya Depression. Despite the fact that each of the studied populations has a unique composition of chromosomal rearrangements and mtDNA haplotypes, higher similarity between the populations of the Muisko-Kuandinskaya Depression and the populations of the Baunt lake valley can still be suggested.

The aim of this study was to determine genome-wide haplotype block structure, extent of linkage disequilibrium (LD) and effective population size using the information obtained from 243 Azerbaijani buffalo (Axiom® Buffalo Genotyping 90 K) using a high density SNP panel. After quality control, 62,141 SNP markers remained for population structure analysis and identification of haplotype blocks. The extent of LD was measured by the square of correlation coefficient (r²) between alleles. The maximum LD varied from 0.25 to 0.29 at a distance of <2.5 kb, and the minimum average values of r² varied from 0.012 to 0.014 at distances ranging from 900 to 1000 kb. Overall, 1693 blocks were observed through the genome. Eleven percent of all SNPs were clustered into haplotype blocks, covering 202 ± 3.4 Mb of the total autosomal genome size. Using formula which relate expected LD to effective population size (N_e), and assuming a constant actual population size, N_e was 422 in our population.

Hemophilia A is a frequent X-linked recessive blood clotting disorder. It is caused by mutations in the F8 gene (locus Xq28) and affects 1 in 5000 newborn boys. The aim of this study was to determine the spectrum of the F8 gene mutations in the Russian patients with hemophilia A. Samples from 117 unrelated families with an incoming diagnosis of hemophilia A were tested by IS-PCR, multiplex PCR, MPS technology, and quantitative MLPA analysis. Mutations were found in all 117 cases. Lof mutations in the VWF gene in the compound-heterozygous state were detected in two patients, two patients had pathogenic variants in the F9 gene, and one patient had a pathogenic variant in the F7 gene. These patients were excluded from further calculations. Intron 22 inversion was detected in 40% of cases, intron 1 inversion in 1% of cases, and gross deletions/duplications in 6% of cases. Point mutations accounted for 53%: missense mutations, 27%; small deletions, 10%; splice site mutations, 6%; nonsense mutations, 5%; and small duplications, 5%. Eighteen mutations were not described previously. Most of them are Lof mutations. Thus, it is necessary to employ different methods for the effective molecular diagnostics of hemophilia A.

The results of genetic and epidemiological study of monogenic hereditary diseases (HD) among children of the Karachay-Cherkess Republics are presented. The surveyed population comprised 410 368 individuals (Cherkessk and ten rural areas), including 90 739 children (22.11%). The examination was performed following the original protocol for genetic-epidemiological studies (developed by the Research Centre for Medical Genetics) making it possible to register not less than 3500 HD and syndromes. One hundred eighty-three nosological forms of HD (922 patients from 764 families) were registered in the child population, including 100 patients with AD (459 patients from 366 families), 60 patients with AR (372 patients from 326 families), and 23 patients with X-linked inheritance (91 patients from 72 families). The structure of diversity is determined, and frequent HDs are described in accordance with the main classification by organ and systemic types of disease: neurological, ophthalmic, genodermatoses, skeletal, hereditary syndromes, and other pathology. There were 55 frequent HDs (30.05%)—the number of patients in this group was 739 (80.15% of sick children). The load of AD, AR, and X-linked pathology for urban and rural child population was calculated. Differences in HD load were identified. On the basis of correlations between the load and F_ST, the causes of the observed differentiation of subpopulations were proposed.

The population features of nuclear and mitochondrial genomes of P. ridibundus Pallas, 1771 and related species of green frogs from Nizhny Novgorod and Sverdlovsk oblasts were investigated for the first time. The existence of the R–E–L population system on the territory of Nizhny Novgorod oblast was confirmed. The presence of heteroplasmy was found in all examined samples of marsh frogs, as well as in hybrid, edible, frogs. These findings indicate the presence of hybridization and introgressions that took place in the history of the studied forms of each of the species. Considerable heterogeneity of animals from the territory of Sverdlovsk oblast in the nuclear and to a higher degree in the mitochondrial genome was demonstrated, which with high probability indicates that the populations existing in this territory originated from multiple introductions. The obtained data characterize the state of population systems, as well as the history of the formation of the modern phylogenogeographic pattern of green frogs on the studied territories.