Studies of the genetic base and polymorphism of bread wheat cultivars aimed at identifying alleles of genes associated with high baking and other economically valuable traits seem to be relevant, since bread wheat, along with all representatives of the Triticeae tribe, has a huge genetic potential for creating cultivars with high technological and rheological properties of grain flour. The aim of this study was sequencing and analysis of the nucleotide sequences of the Glu-B1-1 gene, and analysis of the predicted amino acid sequences of its protein product in three cultivars of bread wheat. Thus, in the course of genotyping cultivars and lines of bread wheat for the Glu-B1-1 gene, in the cultivars ‘Avesta’, ‘Leningradka krupnozernaya’ and line C-75094, previously undescribed changes in the size of amplifiable regions of the Glu-B1-1 gene for high-molecular-weight glutenins were found. Comparative analysis of the nucleotide sequences of these genes with known sequences showed the presence of two deletions in ‘Avesta’ and C-75094 and the presence of seven single-nucleotide substitutions in ‘Leningradka krupnozernaya’. Alignment of the predicted Glu-B1 amino acid sequences of the studied accessions and the standard cultivar carrying the Glu-B1-a allele showed that deletions in the amino acid sequences of ‘Avesta’ and C-75094 accessions are localized in the central domain of the protein and affect the amount of tri-, hexa-, and nonapeptides, and in ‘Leningradka krupnozernaya’, a decrease in GQQ and PGQGQQ by one unit was revealed. In addition, substitutions of five amino acids were found in ‘Leningradka krupnozernaya’. Thus, we have found previously undescribed deletions and substitutions in the nucleotide sequences of the Glu-B1-1 gene for high-molecular-weight glutenins, which lead to changes in amino acid sequences in functionally important regions, namely, in the central domains of protein molecules. The identified mutations can be used for genotyping bread wheat cultivars.

In breeding, biofortification is aimed at enriching the edible parts of the plant with micronutrients. Within the framework of this strategy, molecular screening of collections of various crops makes it possible to determine allelic variants of genes, new alleles, and the linkage of allelic variants with morphophysiological traits. The maize (Zea mays L.) is an important cereal and silage crop, as well as a source of the main precursor of vitamin A – β-carotene, a derivative of the β,β-branch of the carotenoid biosynthesis pathway. The parallel β,ε-branch is triggered by lycopene-ε-cyclase LCYE, a low expression of which leads to an increase in provitamin A content and is associated with the variability    of the 5’-UTR gene regulatory sequence. In this study, we screened a collection of 165 maize inbred lines of Russian selection for 5’-UTR LCYE allelic variants, as well as searched for the dependence of LCYE expression levels on the 5’-UTR allelic variant in the leaves of 14 collection lines. 165 lines analyzed were divided into three groups carrying alleles A2 (64 lines), A5 (31) and A6 (70), respectively. Compared to A2, allele A5 contained two deletions (at positions -267–260 and -296–290 from the ATG codon) and a G₂₅₁→T substitution, while allele A6 contained one deletion (-290–296) and two SNPs (G₂₅₁→T, G₂₆₅→T). Analysis of LCYE expression in the leaf tissue of seedlings from accessions of 14 lines differing in allelic variants showed no associations of the 5’-UTR LCYE allele type with the level of gene expression. Four lines carrying alleles A2 (6178-1, 6709-2, 2289-3) and A5 (5677) had a significantly higher level of LCYE gene expression (~0.018–0.037) than the other 10 analyzed lines (~0.0001–0.004), among which all three allelic variants were present.

The response of 250 common winter wheat breeding lines was investigated for resistance to the causative agent of Puccinia triticina under conditions of an infected field on the territory of Dobrudzha Agricultural Institute – General Toshevo, Bulgaria, during three successive seasons. Twenty lines with different degrees of resistance under field conditions were selected. Multi-pathotype testing was used to study the response of these lines at seedling stage under greenhouse conditions to individual pathotypes of P. triticina. Based on the response of the lines at seedling and adult stages, we found out that 20 % of them carried race-specific resistance. One of the lines (99/08-52) reacted with full resistance to the pathotypes used under greenhouse conditions. The reaction demonstrated by this line coincided with the response of isogenic lines carrying the genes Lr9, Lr19, Lr22a, Lr22b and Lr25. The other three lines (19/06-108, 82/08-43 and 82/08-35) showed a resistant reaction to 6 or 5 of the pathotypes used in the study. Their response partially coincided with the reaction of 5 isogenic lines, and the presence of some of these genes in the above lines is quite possible. Lines carrying this type of resistance are to be subjected to further genetic and breeding investigations to prove the presence of a race-specific gene. Twenty-five percent of the lines combined partial race-specific resistance at seedling stage with the resistance of race non-specific nature at adult stage. Forty percent of all studied lines carried race non-specific resistance, and 15 % of the lines possessed resistance of the “slow rusting” type. As a result of the study we carried out, the lines that demonstrated stable resistance to leaf rust can provide sufficient protection of the host and can be included in the breeding programs for developing varieties resistant to P. triticina.

Walnut is an important horticultural crop, the production of which ranks second among all nut crops. Despite the significant demand in the domestic market in Russia, the industrial production of walnut fruits in Russia is currently underdeveloped. At the same time, there is a need to update the assortment with new highly productive varieties adapted to local agro-climatic conditions and having high quality nuts that are competitive at the world level. An important issue for the successful implementation of breeding programs is a comprehensive study of the gene pool. In this regard, within the framework of the study, the task was to evaluate promising varieties from the collection of the walnut gene pool of the Nikitsky Botanical Gardens and analyze genetic relationships based on microsatellite genotyping. On the basis of the performed phenotypic assessment, the study sample, which included 31 varieties, was divided into several groups according to the main phenotypic traits, such as frost and drought resistance, the start of the growing season, the ripening period, the weight and type of flowering, the weight of the fruit, and the thickness of the endocarp. Varieties with economically valuable traits that can be recommended as promising as initial parental forms in breeding work for resistance to abiotic stress factors have been identified, as well as varieties with increased productivity and large fruit sizes. Based on the analysis of eight SSR markers (WGA001, WGA376, WGA069, WGA276, WGA009, WGA202, WGA089 and WGA054), an analysis of the level of genetic diversity was performed and genetic relationships were established in the studied sample of varieties. Six (for WGA089) to eleven (for WGA276) alleles per locus have been identified. A total of 70 alleles were identified for the eight DNA markers used, with an average value of 8.75. Analysis of SSR genotyping data using Bayesian analysis established the presence of two main groups of genotypes. Taking into account the fact that all the studied varieties are selections from local seed populations in different regions of the Crimean Peninsula, the revealed level of polymorphism may indirectly reflect the level of genetic diversity of the local walnut populations. Furthermore, the presence of two genetically distant groups indicates the presence of two independently formed pools of the autochthonous gene pool of the species Juglans regia L. on the Crimean Peninsula

It is known that different species of animals, when living in the same environmental conditions, can form similar phenotypes. The study of the convergent evolution of several species under the influence of the same environmental factor makes it possible to identify common mechanisms of genetic adaptation. Local cattle and sheep breeds have been formed over thousands of years under the influence of domestication, as well as selection aimed at adaptation to the local environment and meeting human needs. Previously, we identified a number of candidate genes in genome regions potentially selected during domestication and adaptation to the climatic conditions of Russia, in local breeds of cattle and sheep using whole genome genotyping data. However, these data are of low resolution and do not reveal most nucleotide substitutions. The aim of the work was to create, using the whole genome sequencing data, a list of genes associated with domestication, selection and adaptation in Russian cattle and sheep breeds, as well as to identify candidate genes and metabolic pathways for selection for cold adaptation. We used our original data on the search for signatures of selection in the genomes of Russian cattle (Yakut, Kholmogory, Buryat, Wagyu) and sheep (Baikal, Tuva) breeds. We used the HapFLK, DCMS, FST and PBS methods to identify DNA regions with signatures of selection. The number of candidate genes in potentially selective regions was 946 in cattle and 151 in sheep. We showed that the studied Russian cattle and sheep breeds have at least 10 genes in common, apparently involved in the processes of adaptation/selection, including adaptation to a cold climate, including the ASTN2, PM20D1, TMEM176A, and GLIS1 genes. Based on the intersection with the list of selected genes in at least two Arctic/Antarctic mammal species, 20 and 8 genes, have been identified in cattle and sheep, respectively, that are potentially involved in cold adaptation. Among them, the most promising for further research are the ASPH, NCKAP5L, SERPINF1, and SND1 genes. Gene ontology analysis indicated the existence of possible common biochemical path-ways for adaptation to cold in domestic and wild mammals associated with cytoskeleton disassembly and apoptosis.

In this study, 371 Holstein cows from six herds and 26 Holstein bulls, which were used in these herds, were genotyped by the Illumina BovineSNP50 array. For runs of homozygosity (ROH) identification, consecutive and sliding runs were performed by the detectRUNS and Plink software. The missing calls did not significantly affect the ROH data. The mean number of ROH identified by consecutive runs was 95.4 ± 2.7, and that by sliding runs was 86.0 ± 2.6 in cows, while this number for Holstein bulls was lower 58.9 ± 1.9. The length of the ROH segments varied from 1 Mb to over 16 Mb, with the largest number of ROH having a length of 1–2 Mb. Of the 29 chromosomes, BTA 14, BTA 16, and BTA 7 were the most covered by ROH. The mean coefficient of inbreeding across the herds was 0.111 ± 0.003 and 0.104 ± 0.004 based on consecutive and sliding runs, respectively, and 0.078 ± 0.005 for bulls based on consecutive runs. These values do not exceed those for Holstein cattle in North America. The results of this study confirmed the more accurate identification of ROH by consecutive runs, and also that the number of allowed heterozygous SNPs may have a significant effect on ROH data.

Sexual selection is considered as one of the leading factors of evolutionary development. In the conditions of incessant competition, specialized methods of attracting individuals of the opposite sex as well as criteria for assessing the quality of a sexual partner have been formed. In order for animals to rely on signaling from sexual partners, the signal must reflect the morpho-physiological status of animals. A high reproductive efficiency of male mice is a good advantage for mate selection and thus must be somehow demonstrated to potential mates. The aim of our study was to find out if male mice could demonstrate their reproductive efficiency through urine volatile organic compounds. The experiment implies cohabiting one male with two mature females for 6 days. The reproductive success of the male was assessed by the presence or absence of pregnant females. At the same time, naive females, who did not participate in reproduction, assessed the urine of the successful males as more attractive, which was expressed in shorter Latency time of sniffs in the Olfactory test. Using a rapid headspace GC/MS analysis, we have found volatile organic compounds (VOCs) in male urine that correlated with female behavior. It turned out that these substances are derivatives of mouse pheromone 6-hydroxy-6-methyl-3-heptanone. The amplitude of peaks corresponding to this pheromone correlated with the testosterone level in blood and the weight of preputial glands. The amplitude of peaks increased in males after mating with whom the females turned out to be pregnant. It is important to note that body weight, weight of testes, weight of seminal vesicles, weight of preputial glands, and plasma testosterone level alone are not reliable indicators of male reproductive success. Thus, the content of the pheromone 6-hydroxy-6-methyl-3-heptanone in the urine of males can serve as a good predictor of the quality of the male as a sexual partner for female CD-1 mice.

Differentiation of closely related biological species using molecular genetic analysis is important for breeding farm animals, creating hybrid lines, maintaining the genetic purity of breeds, lines and layering. Bos grunniens and Bos taurus differentiation based on STR locus polymorphism will help maintain the genetic isolation of these species and identify hybrid individuals. The aim of this study is to assess the differentiating potential of 15 microsatellite loci to distinguish between domestic yak (B. grunniens) bred in the Kalmak-Ashuu highland region (Kochkor district, Naryn region, Kyrgyz Republic) and cattle (B. taurus) of three breeds (Aberdeen-Angus, Holstein and Alatau) using molecular genetic analysis. The samples were genotyped at 15 microsatellite loci (ETH3, INRA023, TGLA227, TGLA126, TGLA122, SPS115, ETH225, TGLA53, BM2113, BM1824, ETH10, BM1818, CSSM66, ILSTS006 and CSRM60). Twelve of the loci were from the standard markers panel recommended by ISAG. Statistical analysis was performed using GenAlEx v.6.503, Structure v.2.3.4, PAST v.4.03, and POPHELPER v1.0.10. The analysis of the samples’ subpopulation structure using the Structure v.2.3.4 and 15 STR locus genotyping showed that the accuracy of assigning a sample to B. taurus was 99.6 ± 0.4 %, whereas the accuracy of assigning a sample to B. grunniens was 99.2 ± 2.6 %. Of the 15 STRs, the greatest potential to differentiate B. grunniens and B. taurus was found in those with the maximal calculated FST values, including BM1818 (0.056), BM1824 (0.041), BM2113 (0.030), CSSM66 (0.034) and ILSTS006 (0.063). The classification accuracy of B. grunniens using only these five microsatellite loci was 98.8 ± 3.4 %, similar for B. taurus, 99.1 ± 1.2 %. The proposed approach, based on the molecular genetic analysis of 5 STR loci, can be used as an express test in Kyrgyzstan breeding and reproduction programs for B. grunniens.

Healthy human longevity is a global goal of the world health system. Determining the causes and processes influencing human longevity is the primary fundamental goal facing the scientific community. Currently, the main efforts of the scientific community are aimed at identifying the qualitative characteristics of the genome that determine the trait. At the same time, when evaluating qualitative characteristics, there are many challenges that make it difficult to establish associations. Quantitative traits are burdened with such problems to a lesser extent, but they are largely overlooked in current genomic studies of aging and longevity. Although there is a wide repertoire of quantitative trait analyses based on genomic data, most opportunities are ignored by authors, which, along with the inaccessibility of published data, leads to the loss of this important information. This review focuses on describing quantitative traits important for understanding aging and necessary for analysis in further genomic studies, and recommends the inclusion of the described traits in the analysis. The review considers the relationship between quantitative characteristics of the mitochondrial genome and aging, longevity, and age-related neurodegenerative diseases, such as the frequency of extensive mitochondrial DNA (mtDNA) deletions, mtDNA half-life, the frequency of A>G replacements in the mtDNA heavy chain, the number of mtDNA copies; special attention is paid to the mtDNA methylation sign. A separate section of this review is devoted to the correlation of telomere length parameters with age, as well as the association of telomere length with the amount of mitochondrial DNA. In addition, we consider such a quantitative feature as the rate of accumulation of somatic mutations with aging in relation to the lifespan of living organisms. In general, it may be noted that there are quite serious reasons to suppose that various quantitative characteristics of the genome may be directly or indirectly associated with certain aspects of aging and longevity. At the same time, the available data are clearly insufficient for definitive conclusions and the determination of causal relationships.

The development of new biomarkers for prediction and early detection of human diseases, as well as for monitoring the response to therapy is one of the most relevant areas of modern human genetics and genomics. Until recently, it was believed that the function of human Y chromosome genes was limited to determining sex and controlling spermatogenesis. Thanks to occurance of large databases of the genome-wide association study (GWAS), there has been a transition to the use of large samples for analyzing genetic changes in both normal and pathological conditions. This has made it possible to assess the association of mosaic aneuploidy of the Y chromosome in somatic cells with a shorter lifespan in men compared to women. Based on data from the UK Biobank, an association was found between mosaic loss of the Y chromosome (mLOY) in peripheral blood leukocytes and the age of men over 70, as well as a number of oncological, cardiac, metabolic, neurodegenerative, and psychiatric diseases. As a result, mLOY in peripheral blood cells has been considered a potential marker of biological age in men and as a marker of certain age-related diseases. Currently, numerous associations have been identified between mLOY and genes based on GWAS and transcriptomes in affected tissues. However, the exact cause of mLOY and the impact and consequences of this phenomenon at the whole organism level have not been established. In particular, it is unclear whether aneuploidy of the Y chromosome in blood cells may affect the development of pathologies that manifest in other organs, such as the brain in Alzheimer’s disease, or whether it is a neutral biomarker of general genomic instability. This review examines the main pathologies and genetic factors associated with mLOY, as well as the hypotheses regarding their interplay. Special attention is given to recent studies on mLOY in brain cells in Alzheimer’s disease.

Chronic obstructive pulmonary disease (COPD) is a multifactorial disease of the respiratory system which develops as a result of a complex interaction of genetic and environmental factors closely related to lifestyle. We aimed to assess the combined effect of the PI3K/AKT/mTOR signaling pathway (PIK3R1, AKT1, MTOR, PTEN) and sirtuin (SIRT1, SIRT3, SIRT6) genes to COPD risk. SNPs of SIRT1 (rs3758391, rs3818292), SIRT3 (rs3782116, rs536715), SIRT6 (rs107251), AKT1 (rs2494732), PIK3R1 (rs10515070, rs831125, rs3730089), MTOR (rs2295080, rs2536), PTEN (rs701848, rs2735343) genes were genotyped by real-time polymerase chain reaction (PCR) among 1245 case and control samples. Logistic regression was used to detect the association of SNPs in different models. Linear regression analyses were performed to estimate the relationship between SNPs and lung function parameters and smoking pack-years. Significant associations with COPD were identified for SIRT1 (rs3818292) (P = 0.001, OR = 1.51 for AG), SIRT3 (rs3782116) (P = 0.0055, OR = 0.69) and SIRT3 (rs536715) (P = 0.00001, OR = 0.50) under the dominant model, SIRT6 (rs107251) (P = 0.00001, OR = 0.55 for СT), PIK3R1: (rs10515070 (P = 0.0023, OR = 1.47 for AT), rs831125 (P = 0.00001, OR = 2.28 for AG), rs3730089 (P = 0.0007, OR = 1.73 for GG)), PTEN: (rs701848 (P = 0.0015, OR = 1.35 under the log-additive model), and rs2735343 (P = 0.0001, OR = 1.64 for GC)). A significant genotype-dependent variation of lung function parameters was observed for SIRT1 (rs3818292), SIRT3 (rs3782116), PIK3R1 (rs3730089), and MTOR (rs2536). Gene-gene combinations that remained significantly associated with COPD were obtained; the highest risk of COPD was conferred by a combination of G allele of the PIK3R1 (rs831125) gene and GG of SIRT3 (rs536715) (OR = 3.45). The obtained results of polygenic analysis indicate the interaction of genes encoding sirtuins SIRT3, SIRT2, SIRT6 and PI3KR1, PTEN, MTOR and confirm the functional relationship between sirtuins and the PI3K/AKT/mTOR signaling pathway.

One of the most common congenital metabolic disorders is familial hypercholesterolemia. Familial hyper-cholesterolemia is a condition caused by a type of genetic defect leading to a decreased rate of removal of low-density lipoproteins from the bloodstream and a pronounced increase in the blood level of total cholesterol. This disease leads to the early development of cardiovascular diseases of atherosclerotic etiology. Familial hypercholesterolemia is a monogenic disease that is predominantly autosomal dominant. Rare pathogenic variants in the LDLR gene are present in 75–85 % of cases with an identified molecular genetic cause of the disease, and variants in other genes (APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, and others) occur at a frequency of < 5 % in this group of patients. A negative result of genetic screening for pathogenic variants in genes of the low-density lipoprotein receptor and its ligands does not rule out a diagnosis of familial hypercholesterolemia. In 20–40 % of cases, molecular genetic testing fails to detect changes in the above genes. The aim of this work was to search for new genes associated with the familial hypercholesterolemia phenotype by modern high-tech methods of sequencing and machine learning. On the basis of a group of patients with familial hypercholesterolemia (enrolled according to the Dutch Lipid Clinic Network Criteria and including cases confirmed by molecular genetic analysis), decision trees were constructed, which made it possible to identify cases in the study population that require additional molecular genetic analysis. Five probands were identified as having the severest familial hypercholesterolemia without pathogenic variants in the studied genes and were analyzed by whole-genome sequencing on the HiSeq 1500 platform (Illumina). The whole-genome sequencing revealed rare variants in three out of five analyzed patients: a heterozygous variant (rs760657350) located in a splicing acceptor site in the PLD1 gene (c.2430-1G>A), a previously undescribed single-nucleotide deletion in the SIDT1 gene [c.2426del (p.Leu809CysfsTer2)], new missense variant c.10313C>G (p.Pro3438Arg) in the LRP1B gene, and single-nucleotide deletion variant rs753876598 [c.165del (p.Ser56AlafsTer11)] in the CETP gene. All these variants were found for the first time in patients with a clinical diagnosis of familial hypercholesterolemia. Variants were identified that may influence the formation of the familial hypercholesterolemia phenotype.

The etiology of essential hypertension is intricate, since it employs simultaneously various body systems related to the regulation of blood pressure in one way or another: the sympathetic nervous system, renin-angiotensin-aldosterone and hypothalamic-pituitary-adrenal systems, renal and endothelial mechanisms. The pathogenesis of hypertension is influenced by a variety of both genetic and environmental factors, which determines the heterogeneity of the disease in human population. Hence, there is a need to perform research on experimental models – inbred animal strains, one of them being ISIAH rat strain, which is designed to simulate inherited stress-induced arterial hypertension as close as possible to primary (or essential) hypertension in humans. To determine specific markers of diseases, various omics technologies are applied, including metabolomics, which makes it possible to evaluate the content of low-molecular compounds – amino acids, lipids, carbohydrates, nucleic acids fragments – in biological samples available for clinical analysis (blood and urine). We analyzed the metabolic profile of the blood serum of male ISIAH rats with a genetic stress-dependent form of arterial hypertension in comparison with the normotensive WAG rats. Using the method of nuclear magnetic resonance spectroscopy (NMR spectroscopy), 56 metabolites in blood serum samples were identified, 18 of which were shown to have significant interstrain differences in serum concentrations. Statistical analysis of the data obtained showed that the hypertensive status of ISIAH rats is characterized by increased concentrations of leucine, isoleucine, valine, myo-inositol, isobutyrate, glutamate, glutamine, ornithine and creatine phosphate, and reduced concentrations of 2-hydroxyisobutyrate, betaine, tyrosine and tryptophan. Such a ratio of the metabolite concentrations is associated with changes in the regulation of glucose metabolism (metabolic markers – leucine, isoleucine, valine, myoinositol), of nitric oxide synthesis (ornithine) and catecholamine pathway (tyrosine), and with inflammatory processes (metabolic markers – betaine, tryptophan), all of these changes being typical for hypertensive status. Thus, metabolic profiling of the stress-dependent form of arterial hypertension seems to be an important result for a personalized approach to the prevention and treatment of hypertensive disease.