Compilation and functional classification of telomere length-associated genes in humans and other animal species

Telomeres are the terminal regions of chromosomes that ensure their stability while cell division. Telomere shortening initiates cellular senescence, which can lead to degeneration and atrophy of tissues, so the process is associated with a reduction in life expectancy and predisposition to a number of diseases. An accelerated rate of telomere attrition can serve as a predictor of life expectancy and health status of an individual. Telomere length is a complex phenotypic trait that is determined by many factors, including the genetic ones. Numerous studies (including genome-wide association studies, GWAS) indicate the polygenic nature of telomere length control. The objective of the present study was to characterize the genetic basis of the telomere length regulation using the GWAS data obtained during the studies of various human and other animal populations. To do so, a compilation of the genes associated with telomere length in GWAS experiments was collected, which included information on 270 human genes, as well as 23, 22, and 9 genes identified in the cattle, sparrow, and nematode, respectively. Among them were two orthologous genes encoding a shelterin protein (POT1 in humans and pot-2 in C. elegans). Functional analysis has shown that telomere length can be influenced by genetic variants in the genes encoding: (1) structural components of telomerase; (2) the protein components of telomeric regions (shelterin and CST complexes); (3) the proteins involved in telomerase biogenesis and regulating its activity; (4) the proteins that regulate the functional activity of the shelterin components; (5) the proteins involved in telomere replication and/or capping; (6) the proteins involved in the alternative telomere lengthening; (7) the proteins that respond to DNA damage and are responsible for DNA repair; (8) RNA-exosome components. The human genes identified by several research groups in populations of different ethnic origins are the genes encoding telomerase components such as TERC and TERT as well as STN1 encoding the CST complex component. Apparently, the polymorphic loci affecting the functions of these genes may be the most reliable susceptibility markers for telomere-related diseases. The systematized data about the genes and their functions can serve as a basis for the development of prognostic criteria for telomere length-associated diseases in humans. Information about the genes and processes that control telomere length can be used for marker-assisted and genomic selection in the farm animals, aimed at increasing the duration of their productive lifetime

Online resources on gene networks containing human and animal data

Gene networks are molecular genetic systems that ensure the formation of phenotypic characteristics of organisms (molecular, biochemical, structural, morphological, behavioral, etc.) based on  information encoded in their genomes. Reconstruction of gene networks provides a methodological basis for modern systems biology. In this regard, the information on the structural and functional organization of gene networks accumulated in modern databases is extremely valuable. This review characterizes a number of Internetaccessible information resources oriented to humans and animals and containing data on gene networks and their functional modules. Without pretending to fully cover all information resources containing data related to humans and animals on the subject, the current review was created to report the current status of the problem and to present the criteria according to which we propose to evaluate the utility of webresources for specific research tasks. On this basis, we compiled and characterized a collection of databases containing information on metabolic and signaling pathways, as well as pathways of regulation of biological processes at the cellular and organismal levels. In addition, we observed the characteristics of several well­known databases containing data on interactions between biomolecules of various types. The following characteristics of databases were considered: (1) the types of information accumulated in the databases; (2) methods of data presentation; (3) methods of data collection; (4) data sources; (5) special search tools and options for data analysis. A comparison of the above characteristics showed that the databases are very heterogeneous according to their scopes, sources and types of data, interfaces, as well as according to their search options and data analysis tools. It was concluded that at the first step of the gene network reconstruction it is important to form a full set of information resources from which the data can be obtained. The web portals accumulating information about the databases that may be useful for the reconstruction and analysis of gene networks are specified

Arctic Art & Culture

The popular science journal includes the materials about educational, research, scientific and practical activity of the team from the Arctic State Institute of Culture and Arts and the Northern Forum regions facilitating the image-making of the North and Arctic

Prioritization of genes associated with the pathogenesis of leukosis in cattle

Selection by means of genetic markers is a promising approach to the eradication of infectious diseases in farm animals, especially in the absence of effective methods of treatment and prevention. Bovine leukemia virus (BLV) is spread throughout the world and represents one of the biggest problems for the livestock production and food security in Russia. However, recent genome-wide association studies have shown that sensitivity/resistance to BLV is polygenic. The aim of this study was to create a catalog of cattle genes and genes of other mammalian species involved in the pathogenesis of BLV-induced infection and to perform gene prioritization using bioinformatics methods. Based on manually collected information from a range of open sources, a total of 446 genes were included in the catalog of cattle genes and genes of other mammals involved in the pathogenesis of BLV-induced infection. The following criteria were used to prioritize 446 genes from the catalog: (1) the gene is associated with leukemia according to a genome-wide association study; (2) the gene is associated with leukemia according to a case-control study; (3) the role of the gene in leukemia development has been studied using knockout mice; (4) protein-protein interactions exist between the gene-encoded protein and either viral particles or individual viral proteins; (5) the gene is annotated with Gene Ontology terms that are overrepresented for a given list of genes; (6) the gene participates in biological pathways from the KEGG or REACTOME databases, which are over-represented for a given list of genes; (7) the protein encoded by the gene has a high number of protein-protein interactions with proteins encoded by other genes from the catalog. Based on each criterion, a rank was assigned to each gene. Then the ranks were summarized and an overall rank was determined. Prioritization of 446 candidate genes allowed us to identify 5 genes of interest (TNF, LTB, BOLA-DQA1, BOLA-DRB3, ATF2), which can affect the sensitivity/resistance of cattle to leukemia

Effects of turbulent mixing on critical behaviour in the presence of compressibility: Renormalization group analysis of two models

Critical behaviour of two systems, subjected to the turbulent mixing, is studied by means of the field theoretic renormalization group. The first system, described by the equilibrium model A, corresponds to relaxational dynamics of a non-conserved order parameter. The second one is the strongly non-equilibrium reaction-diffusion system, known as Gribov process and equivalent to the Reggeon field theory. The turbulent mixing is modelled by the Kazantsev-Kraichnan "rapid-change" ensemble: time-decorrelated Gaussian velocity field with the power-like spectrum k^{-d-\xi}. Effects of compressibility of the fluid are studied. It is shown that, depending on the relation between the exponent \xi and the spatial dimension d, the both systems exhibit four different types of critical behaviour, associated with four possible fixed points of the renormalization group equations. The most interesting point corresponds to a new type of critical behaviour, in which the nonlinearity and turbulent mixing are both relevant, and the critical exponents depend on d, \xi and the degree of compressibility. For the both models, compressibility enhances the role of the nonlinear terms in the dynamical equations: the region in the d-\xi plane, where the new nontrivial regime is stable, is getting much wider as the degree of compressibility increases. In its turn, turbulent transfer becomes more efficient due to combined effects of the mixing and the nonlinear terms.Comment: 25 pages, 4 figure

Haplotype analysis of APOE intragenic SNPs

BACKGROUND: APOE epsilon4 allele is most common genetic risk factor for Alzheimer\u27s disease (AD) and cognitive decline. However, it remains poorly understood why only some carriers of APOE epsilon4 develop AD and how ethnic variabilities in APOE locus contribute to AD risk. Here, to address the role of APOE haplotypes, we reassessed the diversity of APOE locus in major ethnic groups and in Alzheimer\u27s Disease Neuroimaging Initiative (ADNI) dataset on patients with AD, and subjects with mild cognitive impairment (MCI), and control non-demented individuals. RESULTS: We performed APOE gene haplotype analysis for a short block of five SNPs across the gene using the ADNI whole genome sequencing dataset. The compilation of ADNI data with 1000 Genomes identified the APOE epsilon4 linked haplotypes, which appeared to be distant for the Asian, African and European populations. The common European epsilon4-bearing haplotype is associated with AD but not with MCI, and the Africans lack this haplotype. Haplotypic inference revealed alleles that may confer protection against AD. By assessing the DNA methylation profile of the APOE haplotypes, we found that the AD-associated haplotype features elevated APOE CpG content, implying that this locus can also be regulated by genetic-epigenetic interactions. CONCLUSIONS: We showed that SNP frequency profiles within APOE locus are highly skewed to population-specific haplotypes, suggesting that the ancestral background within different sites at APOE gene may shape the disease phenotype. We propose that our results can be utilized for more specific risk assessment based on population descent of the individuals and on higher specificity of five site haplotypes associated with AD

The perspective soft spring wheat variety Semenovna is the result of international cooperation

The research is aimed at studying economically valuable traits and genetic control of resistance to leaf-stem diseases, photoperiodic reaction and short stemming of soft spring wheat variety Semenovna, created by scientists of the Omsk Agrarian Scientific Center (Russia) and the North Kazakhstan Agricultural Experimental Station (Kazakhstan). Using methods of state variety testing, molecular genetics and in vitro methods, morphological features of a new variety, features of its development have been described, the yield level at different ecological test points for three years (2015-2017) has been analyzed. The studies conducted at two ecological points made it possible to select a medium-sized promising line of soft spring wheat (Lutescens 354/04-6), which was transferred to the State Registration Service of the Republic of Kazakhstan and after two years of testing was included into the State Register of the Republic of Kazakhstan under the name Semenovna (patent No. 1023). In terms of grain quality, it was at the level of valuable wheat, exceeded the standard in protein content by 1-2 % and raw gluten by 3-4 %. The new medium-ripe Semenovna variety combines increased yield (2.73-4.40 t/ha) with resistance to drought (resistance index Ir = 0.57), brown and stem rust (IU = 0.00-0.23). The genotype of the variety contains wheat-rye translocation 1RS.1BL (with a cluster of Lr26/Sr31/Pm8/Yr9 genes). The medium-stem variety carries the Rht8b allele in its genotype (174 bp)  and is photosensitive to the length of the day (allele 414 bp). The parameters of ecological plasticity of the new variety are determined: linear regression coefficient (bi = 1.08), stability index (σd2 = 0.27)

Dissecting the role of single nucleotide polymorphism of lymphotoxin beta gene during pig domestication using bioinformatic and experimental approaches

Studies of wild and laboratory animals have revealed a trade-off between reproductive success and immunity. Therefore, it is likely that domestication favored selection of individuals with high reproductive performance but low immunity. The low responsiveness of the immune system could become hereditary through fixation of genes with “unfavorable” mutations in populations. The objectives of this work are: 1) determination of frequencies of genotypes and alleles of the rs340283541 SNP in the gene for the lymphotoxin beta (LTB) cytokine in pigs of domestic breeds and wild boars; 2) investigation of the expression of LTB mRNA in minipigs with different genotypes, and 3) bioinformational analysis of the putative functional role of the SNP. The frequency of the GG genotype in the wild boar sample was significantly lower than in the pooled sample of domestic pigs. The LTB mRNA expression rate in the lymph node of minipigs with genotype GG tended to increase (p < 0.06) in comparison with carriers o allele A. The rs340283541 SNP occurs in a DNA motif highly conservative among 11 mammalian species; thus, it may be of functional significance. Context analysis shows that allele A has putative binding sites for  transcription factors BRN-2 and AP-1, whereas allele G has binding sites for transcription factors RFX1, ISGF3 (site ISRE), and USF expressed in cells of the immune system. Thus, pig domestication was accompanied by an increase in the frequency of the GG genotype for the rs340283541 SNP, occurring in the 3’ region of the LTB gene. It is likely that the GG genotype is associated with elevated LTB mRNA expression in the lymph node tissue. This increase may be related to the formation of binding sites for RFX1, ISRE, and USF and/or disruption of binding sites for BRN-2 and AP-1. A linkage disequilibrium between rs340283541 and another functionally significant mutation in LTB is also conceivable

Single nucleotide polymorphism rs110861313 in the intergenic region of chromosome 23 is associated with the development of leukosis in the Russian Black Pied cattle

In recent years, using a genome-wide association study (GWAS), a number of single nucleotide polymorphisms (SNPs) have been suggested to be associated with susceptibility to leukemia in cattle. However, all studies have been done with purebred Holstein cows and their hybrids. In this regard, it is important to confirm the functional role of polymorphisms previously identified in a GWAS study in Russian cattle breeds. The aim of this study was to verify the association between rs110861313 in the intergenic region of bovine chromosome 23 and leukemia in the Russian Black Pied cattle. Based on the levels of bovine leukemia virus (BLV)-specific antibodies detected in serum using serodiagnostic techniques, animals were divided into three groups: healthy animals (n = 115), asymptomatic virus carriers (n = 145) and animals with leukemia (n = 107). Genotyping of rs110861313 was carried out using polymerase chain reaction followed by analysis of restriction fragment length polymorphisms. A significant decrease in the frequency of the A/A genotype (11.2 %) was revealed in animals with persistent lymphocytosis compared to virus carriers (27.6 %) (p < 0.002). At the same time, the frequency of animals with the C/C genotype in animals with persistent lymphocytosis (41.1 %) was significantly higher than that of virus carriers (21.4 %) (p < 0.001). In this case, asymptomatic virus carriers can be considered a more suitable control than healthy animals that have not been in contact with the virus. According to bioinformatics analysis, resistance to BLV can be due to the presence of the transcription factor FOXM1 binding site in the region of rs110861313. FOXM1 is expressed in immune cells and can potentially affect the expression of the neighboring genes (LY6G5B, GPANK1, ABHD16A, LY6G6F, LY6G6E, CSNK2B, ApoM). Thus, we found that SNP rs110861313 in the intergenic region of bovine chromosome 23 is associated with the development of leukemia following BLV infection in the Russian Black Pied cattle