Objective. To conduct molecular genetic studies of patients with myocardial infarction (MI) for polymorphisms of genes associated with the metabolism of antithrombotic drugs, and to evaluate their relationship with clinical and laboratory parameters.Materials and methods. The material for molecular genetic studies was venous blood of patients with acute MI who underwent percutaneous coronary intervention (PCI) with stenting of the infarct-related artery. This data sample included 69 patients, of which 58 (84.1%) were male and 11 (15.9%) were female.The technology based on competitive allele-specific polymerase chain reaction (PCR) was used for genotyping. The analysis was performed for 26 polymorphisms of the genes CDC42BPA, RPS20P10, P2RY12, MED12L, PPM1K, LOC124900191, PACRG-AS1, LINC02854, SOCS5P1, ABCB1, PON1, NCOA2, CER1, LIPM, CYP2C18, CYP2C19, CYP2C9, CRTAC1, R3HCC1L, MICAL2, LOC105376637, CES1, ZFHX3-AS1 and WFDC1. The entire list of necessary clinical and laboratory tests was performed according to the protocols for examination and treatment of cardiovascular diseases of the Ministry of Health of the Republic of Belarus.Statistical analysis was performed using Microsoft Excel and SPSS v.20.0. The study design was approved by the Ethics Committee of the Republican Scientific and Practical Center “Cardiology” and the Bioethics Committee of the Institute of Genetics and Cytology of the National Academy of Sciences of Belarus.Results. In the presence of the minor allele G for the rs35835168 polymorphism, the level of alanine aminotransferase (ALT) was lower than in the presence of the CC genotype - 33.29 U / L and 55.45 U / L, respectively (p=0.023); in the presence of the minor allele G for the rs12598219 polymorphism, the atherogenic coefficient (AC) was higher than in the presence of the AA genotype - 4.66 and 3.79, respectively (p=0.032); in the presence of the GG genotype for the rs12598219 polymorphism, the prothrombin time (PT) was higher than in the presence of the alternative genotype - 19.50 and 12.30, respectively (p=0.002); in the presence of the TT genotype for the rs7584466 polymorphism, the PT indicator was higher than in the presence of the minor allele - 12.98 and 11.87, respectively (p=0.026); in the presence of the AA genotype for the rs303500 polymorphism, the thrombin time (TT) indicator was higher than in the presence of the alternative genotype - 17.99 and 15.30, respectively (p=0.039); in the presence of the AA genotype for the rs7714373 polymorphism, the TT indicator was higher than in the presence of the AG / GG genotypes - 24.75 and 16.38, respectively (p=0.018); For polymorphisms rs1799853, rs7584466, rs7714373 and rs139496757 there was an association with the fibrinogen level; in the presence of the minor allele A for rs7714373, the ASPI value was 15.82, in the presence of the GG genotype - 29.66 (p=0.003); in the presence of the CC genotype, the ASPI value was 62.00, which significantly exceeds the ASPI value in the presence of the CT/TT genotype - 24.92 (p=0.012).Conclusion. Therefore, we identified associations between clinical and laboratory parameters of patients with MI and a number of polymorphisms rs12248560, rs12598219, rs139496757, rs1799853, rs303500, rs35835168, rs55670713, rs71546150, rs7584466 and rs7714373.
Based on the data presented in the public domain on the GEO-NCBI Platform for 21 projects to determine the genomewide DNA methylation profile using the Infinium Human Methylation 450K BeadChip (Illumina©), we calculated the prediction error for chronological age values in percentage terms and MAD using three different algorithms: linear regression, generalized regression neural networks and multilayer feedforward neural networks. For each algorithm, we have provided guidelines to select the samples for the study. We have also proved that the minimum and sufficient sample size, an increase in which does not lead to a significant decrease in the MAD value, is at least 200 people.
Based on bioinformatics and statistical analysis of GEO-projects on the determination of the genome-wide profile of human DNA methylation, a list of CpG dinucleotides with high predictive potential was formed to design models allowing to predict human age by sperm samples. The methylation level was determined for 467 males from the Republic of Belarus. The correlation coefficients R were calculated, and mathematical models for determining the age of an individual were constructed. The average value of the accuracy of age prediction by sperm samples using 5 CpG-dinucleotides was 3 years. The results obtained will be used as a basis for the development of calculators for predicting the age of an individual based on the traces of biological character for forensic experts.
On the basis of bioinformatics and statistical analysis of GEO projects to determine the genome-wide profile of human DNA methylation, a list of 41 CpG dinucleotides with high predictive potential was formed to create models for predicting human age from biological samples. The methylation level was determined for 1208 samples of individuals from the Republic of Belarus (275—blood, 466—buccal epithelium, 467—semen). The correlation coefficients R were calculated, and mathematical models for determining the age of individual were constructed. The mean value of the accuracy of age prediction from blood samples using 12 CpG dinucleotides was 3.4 years (3.3 for men, 3.5 for women); from buccal epithelium samples using 6 CpG dinucleotides, it was 4.6 years (4.5 for men, 4.7 for women); from semen samples using 5 CpG dinucleotides, it was 3.0 years. The results obtained will be used as a basis for the development of calculators for predicting the age of an individual based on traces of biological character for forensic experts.
The study assessed the genetic diversity of commercial varieties and feral populations of oilseed rape (Brassica napus L.) grown in the Republic of Belarus according to the genotyping data of 7 microsatellite loci – Na12D08, Ol12D04-1, Ol12D04-2, Ra2A05, Na10H03, Na14H11, Ol11B05. The following parameters were calculated: the average number of alleles per locus, the effective number of alleles, the levels of expected and observed heterozygosity, % of polymorphic loci. The results indicate a greater genetic diversity in feral oilseed rape populations. According to the cluster analysis, one feral population fell into a cluster of commercial varieties and demonstrated similarities with the variety Atora, which indicates its recent wildness and the preservation of the genetic characteristics inherent in cultivated varieties. The variety Mercedes was clustered together with samples of feral populations, which may indicate its hybrid origin. An analysis of the structure of the genotype distribution in the Structure software showed the division into three clusters – commercial varieties, feral populations and samples of B. rapa. The established genetic divergence between feral populations and commercial varieties indicates that feral oilseed rape is able to maintain persistent populations inBelarus. In practice, this should be taken into account while assessing the environmental risk when transgenic rape is released into the environment. When cultivating transgenic rapeseed, special attention should be paid to measures to prevent the occurrence of its free-growing populations.
As part of the study, DNA markers for local races L. maculans were identified and found that the AvrLm4-7 sequence in the selected fungus population is specifically recognized by the resistance Rlm4 and Rlm7 genes. The SCAR marker BN204 was identified, which allows us to identify homozygous and heterozygous plants carrying the Rlm4 gene. The work collection, including 22 varieties and 39 hybrids of rape, was analyzed using the DNA marker BN204. PCR results allowed us to establish that the number of individual plants with the resistance Rlm4 gene was higher than the number of stable forms characterized by the infection of leaf explants with pathogen races carrying the AvrLm4-7 sequence. It is supposed that these individual plants contain the Rlm4 gene, but they lack the Rlm7 gene.
The composition and quantity of high-molecular-weight glutenin subunits plays an important role in determining the bread-making quality of wheat. Molecular-genetic analysis of allelic composition of high-molecular-weight glutenin genes in 102 bread wheat cultivars and lines from different geographical regions was conducted. Three alleles at the Glu-A1 locus, nine alleles at the Glu-B1 locus, and two alleles at the Glu-D1 locus were identified. Among the investigated cultivars and lines, 21 were characterized by intracultivar polymorphism. High allelic variation of high-molecular-weight glutenin subunit genes was shown for the collection: 21 and 9 combinations were defined in monomorphic and polymorphic cultivars and lines, respectively. However, the major part of the collection (66.7%) contained four allelic combinations: Glu-A1b Glu-B1c Glu-D1d, Glu-A1b Glu-B1c Glu-D1-2a, Glu-A1a Glu-B1c Glu-D1d, and Glu-A1b Glu-B1c Glu-D1d/Glu-D1-2a. Fourteen cultivars of bread wheat were selected, and they were characterized by a favorable allelic composition of Glu-1 loci.