Genetic polymorphism and rare variants of alpha 1-antitrypsin in the population of Moscow. Research using isoelectric focusing on an ultrathin gel

The data are presented on distribution of subtypes and rare variants of Pi system for Moscow population. Serum samples were obtained from 210 families of healthy newborn (father-mother-newborn) from several Moscow maternity hospitals. Phenotypes of alpha 1-antitrypsin were detected by isoelectric focusing in ultrathin layer polyacrylamide gel with the range 3.5-6. In this study 5 common PiM subtypes (except M3M3) were found. The observed distribution of Pi subtypes shows a good agreement with the Hardi-Weinberg equation. The gene frequencies of the subtypes estimated for Moscow population were as follows: PiM1-0.7662, PiM2-0.1779, PiM3-0.0398. They did not show any difference from the corresponding frequencies in other European populations. In the course of our studies, some rare phenotypes, such as MS, MZ, FM and IM that were observed in most European populations, were detected. Furthermore, a very rare variant (MT) which had been only once revealed in European population, was found. The total gene frequency of all rare variants was 0.0162.     

Acclimatization of salmon Oncorhynchus gorbuscha (Walbaum) in the European north: data from restriction analysis of mtDNA

Pink salmon spawners introduced into the White Sea basin (the Umba River) were compared to the spawners from the basin of the Sea of Okhotsk (the Ola River) using restriction analysis of two fragments of mitochondrial DNA (mtDNA). One of the fragments included genes ND5/ND6, the other, the cytochrome b gene and the control region. It was found that mtDNA variation and diversity at the earlier examined nuclear allozyme genes significantly decreased in the odd broodline of pink salmon 8 years after the introduction. The haplotype diversity in the even broodline was considerably lower than in the odd broodline exhibiting virtually no change two generations after the introduction. Based on the results obtained, a possible role of these changes in adaptation of White Sea pink salmon from the odd broodline to the new environment is discussed.     

Genetic differentiation of pink salmon oncorhynchus gorbuscha Walbaum in the Asian part of the range

Genetic variation at 19 allozyme (including 11 polymorphic) and 10 microsatellite loci was examined in the population samples of odd- and even-broodline pink salmon from the southern part of Sakhalin Island, Southern Kuril Islands, and the northern coast of the Sea of Okhotsk. The estimates of relative interpopulation component of genetic variation over the allozyme loci, per broodline, were on average 0.43% (GST), while over the microsatellite loci it was 0.26% (the theta(ST) coefficient, F-statistics based on the allele frequency variance), and 0.90% (the rho(ST) coefficient, R-statistics based on the allele size variance). The values of interlinear component constituted 2.34, 0.31, and 1.05% of the total variation, respectively. Using the allozyme loci, statistically significant intralinear heterogeneity was demonstrated among the regions, as well as among the populations of Southern Sakhalin Island. Multivariate scaling based on the allozyme data demonstrated regional clustering of the sample groups, representing certain populations during the spawning run or in different years. Most of the microsatellite loci examined were found to be highly polymorphic (mean heterozygosity > 0.880). The estimates of interlinear, interregional, and interpopulation variation over these loci in terms of theta(ST) values were substantially lower than in terms of rho(ST) values. Regional genetic differentiation, mostly expressed at the allozyme loci among the populations from the northern and southern parts of the Sea of Okhotsk (i.e., between the Sakhalin and Kuril populations), was less expressed at the microsatellite loci. The differentiation between these regions observed can be considered as the evidence in favor of a large-scale isolation by distance characterizing Asian pink salmon. It is suggested that in pink salmon, low genetic differentiation at neutral microsatellite loci can be explained by extremely high heterozygosity,of the loci themselves, as well as by the migration gene exchange among the populations (the estimate of the genetic migration coefficient inferred from the "private" allele data constituted 2.6 to 3.4%), specifically, by the ancient migration exchange, which occurred during postglacial colonization and colonization of the range.     

MALINA: a web service for visual analytics of human gut microbiota whole-genome metagenomic reads

MALINA is a web service for bioinformatic analysis of whole-genome metagenomic data obtained from human gut microbiota sequencing. As input data, it accepts metagenomic reads of various sequencing technologies, including long reads (such as Sanger and 454 sequencing) and next-generation (including SOLiD and Illumina). It is the first metagenomic web service that is capable of processing SOLiD color-space reads, to authors’ knowledge. The web service allows phylogenetic and functional profiling of metagenomic samples using coverage depth resulting from the alignment of the reads to the catalogue of reference sequences which are built into the pipeline and contain prevalent microbial genomes and genes of human gut microbiota. The obtained metagenomic composition vectors are processed by the statistical analysis and visualization module containing methods for clustering, dimension reduction and group comparison. Additionally, the MALINA database includes vectors of bacterial and functional composition for human gut microbiota samples from a large number of existing studies allowing their comparative analysis together with user samples, namely datasets from Russian Metagenome project, MetaHIT and Human Microbiome Project (downloaded fromhttp://hmpdacc.org). MALINA is made freely available on the web athttp://malina.metagenome.ru. The website is implemented in JavaScript (using Ext JS), Microsoft .NET Framework, MS SQL, Python, with all major browsers supported.     

Species-Specific Random Amplified Monomorphic DNA

Intra- and interspecific variability of total DNA isolated from haploid megagametophytes of coniferous species was examined using polymerase chain reaction with random primers. Based on this technique, one can with certainty detect heterozygosity at gene loci carrying null alleles and thus reveal cryptic intraspecific genetic variation. Large population samples were used. Along with random amplified polymorphic DNA, i.e., widely known fragments (amplicons) polymorphic within a species, we found invariant loci lacking individual or geographic variability but differentiating species within genera and other taxa. This DNA was termed RAMD (random amplified monomorphic DNA) to distinguish it from polymorphic DNA. Our findings suggest that genetic monomorphism of species and the dual structure of the eukaryotic genome can be detected at the DNA level as was previously shown for protein gene markers.     

Population Genetic Analysis of the Association Between the <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">P53</Emphasis> Gene Polymorphisms and the Risk of Sporadic Breast Cancer

Polymorphism of two tumor-suppressor genes, BRCA1 and P53, was examined. DNA was extracted from blood leukocytes of the women affected with breast cancer (N = 151) and of the women with no clinical symptoms of tumor diseases (N = 191). Typing of the polymorphic variants was performed using PCR-RFLP method. It was demonstrated that the genetic structure of the patient group (taking into consideration BRCA1 and P53 polymorphic variants) differed from that of the control group. The group of genotypes, found exclusively among the patients, as well as the group of “ resistant” genotypes revealed predominantly among the controls, was described. Detection of the genotype A ₁ A ₁ B ₁ B ₁ S ₁ S ₁ C ₁ C ₁ F ₁ F ₁ J ₂ J ₂, whose frequency in control group was eight times higher than in the patient group, was an additional confirmation of the existence of “resistant” genotypes. These findings point to the association between the combinations of the BRCA1 and P53 allelic variants and the risk of breast cancer.__________Translated from Genetika, Vol. 41, No. 8, 2005, pp. 1115–1124.Original Russian Text Copyright © 2005 by Tarasov, Aslanyan, Tsyrendorzhiyeva, Garkavtseva, Lyubchenko, Altukhov, Mel’nik.     

Population genetic study of Russian cosmonauts and test subjects: Genetic demographic parameters and immunogenetic markers

Genetic demographic characteristics and immunogenetic markers (blood groups ABO, Rhesus, MNSs, P, Duffy, Kidd, and Kell) have been studied in a group of 132 Russian cosmonauts and test subjects (CTSG). Analysis of pedigrees has shown a high exogamy in the preceding generations: almost half of the subjects have mixed ethnic background. According to the results of genetic demographic analysis, a sample from the Moscow population was used as control group (CG). Comparison between the CTSG and CG has demonstrated significant differences in genotype frequencies for several blood group systems. The CTSG is characterized by a decreased proportion of rare interlocus genotypic combinations and an increased average heterozygosity. Analysis of the distributions of individual heterozygosity for loci with codominant expression of alleles has shown that the carriers of highly heterozygous genotypes are more frequent in the CTSG. Taking into account that the CTSG has been thoroughly selected from the general population, it is concluded that heterozygosity is related to successful adaptation to a space flight.     

Genetic Changes in Pink Salmon Oncorhynchus gorbuscha Walbaum during Acclimatization in the White Sea Basin

Genetic parameters of pink salmon introduced into the White Sea basin in 1985 and 1998 were compared to the corresponding parameters of the donor population from the Ola River (Magadan oblast). The detected genetic differences indicate that colonization of a new area is accompanied by impoverishment of the gene pool of the native population. This effect was particularly marked in the odd-year broodline of pink salmon introduced in 1985. The probable causes of these genetic changes are discussed.     

Proteome–Metabolome Profiling of Ovarian Cancer Ascites Reveals Novel Components Involved in Intercellular Communication

Ovarian cancer ascites is a native medium for cancer cells that allows investigation of their secretome in a natural environment. This medium is of interest as a promising source of potential biomarkers, and also as a medium for cell–cell communication. The aim of this study was to elucidate specific features of the malignant ascites metabolome and proteome. In order to omit components of the systemic response to ascites formation, we compared malignant ascites with cirrhosis ascites. Metabolome analysis revealed 41 components that differed significantly between malignant and cirrhosis ascites. Most of the identified cancer-specific metabolites are known to be important signaling molecules. Proteomic analysis identified 2096 and 1855 proteins in the ovarian cancer and cirrhosis ascites, respectively; 424 proteins were specific for the malignant ascites. Functional analysis of the proteome demonstrated that the major differences between cirrhosis and malignant ascites were observed for the cluster of spliceosomal proteins. Additionally, we demonstrate that several splicing RNAs were exclusively detected in malignant ascites, where they probably existed within protein complexes. This result was confirmed in vitro using an ovarian cancer cell line. Identification of spliceosomal proteins and RNAs in an extracellular medium is of particular interest; the finding suggests that they might play a role in the communication between cancer cells. In addition, malignant ascites contains a high number of exosomes that are known to play an important role in signal transduction. Thus our study reveals the specific features of malignant ascites that are associated with its function as a medium of intercellular communication.Ovarian cancer is the sixth most frequently occurring cancer among the gynecological cancers and accounts for about 5% of all new female cancer cases according to the 2012 data (World Health Organization International Agency for Research on Cancer www.globocan.iarc.fr). Epithelial ovarian cancer registered in 90% of ovarian cancer cases. The rate of mortality from ovarian cancer holds first place among the other gynecological cancers, largely because of the asymptomatic progression of the disease, especially at its early stages, and a lack of adequate screening tests, which leads to late detection, typically only after the cancer has spread to adjacent structures. In such a case, the five-year survival rate is only 25% to 40%, whereas it can be as high as 90% if the cancer is diagnosed early. Unfortunately, ovarian cancer is diagnosed early in less than 20% of the total number of cases (International Agency for Research on Cancer). The main methods for primary diagnostics include transvaginal ultrasound and blood biomarker analyses such as with cancer antigen 125 (CA125),¹ epididymis protein-4 (HE4), and the OVA1 multiparametric (CA125, β2-microglobulin, transferrin, and apolipoprotein A1) tests. The OVA1 test is mainly applied to evaluate the malignancy of a tumor-like pelvic mass, and the other two markers are used to monitor disease progress and estimate treatment efficacy, as they are not highly specific for ovarian cancer and thus produce a high percentage of false-positive results (1). Therefore, the search for specific and sensitive markers for the early diagnosis of ovarian cancer is an urgent problem, although the development of new, efficient methods for treatment of the disease at late stages also remains of critical importance.One of the symptoms associated with late-stage ovarian cancer is excessive fluid accumulation in the abdominal cavity, known as ascites. Mechanisms of malignant ascites formation involve lymph obstruction, activation of mesothelial cells as a result of the metastatic process, and increased vessel permeability due to the secretion of growth factors (2, 3). Therefore, malignant ascites is enriched by tumor cells and soluble growth factors that may be associated with the processes of invasion and metastasis. Thus, ascites provides a native medium for cancer cells and creates an opportunity to investigate the ovarian cancer cell secretome in its natural environment (as distinct from cancer cell cultures in vitro) (2).Omics studies enable us to understand physiological information at different levels (4–7). Considering the highly diverse features of information obtained from each omics platform, one could expect that combinations of different omics should provide highly comprehensive views on special features of the cancer cell secretome. Studies of ascites with the use of omics technologies could not only help us understand the peculiarities of the vital activity of cancer cells in the organism, but also elaborate new therapeutic methods. However, until now, proteomic studies of ovarian cancer ascites have been exceptionally directed at the search for potential biomarkers of this cancer (3, 8–10). Investigation of ascites is also interesting beyond the protein level. In particular, small molecules—metabolites—are known to be involved in intercellular communication. However, in metabolome studies, to our knowledge, metabolites from ovarian cancer ascites have not been explored at all; only metabolomic analysis of urine and serum has been described in the literature for this type of cancer (11–13).It is important to note that ascites accumulation can be caused by various pathologies—for example, liver cirrhosis (81% of all cases), heart diseases (2%), tuberculosis (3%), and 10% of all cases associated with malignancy (10%). The most common cancer associated with ascites is ovarian cancer, accounting for 38% of malignant ascites occurring in females (2). In this study, we compared ascites of different etiologies, formed in the course of ovarian cancer and portal alcoholic cirrhosis. Thus, we not only extended our knowledge of the protein composition and filled in gaps regarding the metabolome, but also elucidated specific features of malignant ascites composition.