Search

Circulating vitamin D levels and the risk of osteoporosis have significant inheritance. Single nucleotide polymorphisms (SNPs) in the GC, DHCR7/NADSYN1, CYP2R1, CYP24A1, and SEC23A genes have shown significant association with these conditions in previous genome-wide association studies (GWAS). Objective: to study the frequency of alleles associated with circulating levels of vitamin D and osteoporosis in the cohort of Ukrainians, as well as to compare the frequencies of these variants with individuals of Western and Northern European origin. Materials and Methods. This paper presents the results of the study of the frequencies of genomic variants associated with vitamin D levels and osteoporosis in a cohort of 97 Ukrainians based on genome data obtained by whole genome sequencing (WGS), as well as comparing their frequencies with the combined European population (CEU) of the "1000 genomes" project (persons of Western and Northern European ancestry). Files with the primary publicly available genomic data of Ukrainians were annotated using ANNOVAR and SNPEff software using the reference database of the human genome version hg38. Comparison of allele frequencies between populations was performed using Fisher's exact test using the number of alleles in the two studied populations and the construction of conjugated 2x2 tables. Results. It was found that of the 22 single nucleotide polymorphisms included in the analysis, 10, namely rs2282679; rs4855; rs10033936; rs3755967; rs17467825; rs12639968; rs1155563; rs17216707; rs10745742; rs180119, significantly differ in the Ukrainian cohort comparatively to CEU. Using correlation analysis, we also found that the genotypes of SNPs rs3755967, rs17467825, rs2282679 and rs4855 in Ukrainians are completely correlated with each other (r = 1), which means that they are in a state of complete linkage in Ukrainians of the given cohorts. Conclusion. Such findings may be the evidence of evolutionary and adaptation processes in the regulation of vitamin D levels and bone mineral density in the population of Ukraine and requires further studies of phenotype-genotype relationship.

Pituitary-dependent excess of GH may be a genetic disease, the literature describes a number of mutations that lead to an isolated excess of growth hormone, or as a symptom in a syndromic disease. The goal is to conduct a genome-wide search for associations of the patients with acromegaly genome to identify known mutations in the genes associated with this disease in adjacent sites. Create the first reference genomic base of Ukrainian patients with acromegaly to further study the causes of this disease and the introduction of personalized treatment in accordance with the genetic profile. Results. This article presents the results of a genome-wide search of the genome of 5 patients with acromegaly. The genotyping panel we used allowed us to identify 154 single-nucleotide polymorphisms in the genes that were previously described as associated with acromegaly. One patient is heterozygous for the alternative allele (AG) of SNPs rs33927012 of SDHB gene. This alternative allele is extremely rare in the world population (0.9%, in the European population — 2%). It is described as harmful by two analytical systems. Mutations in the SDHB gene lead to structural changes in the SDH protein (succinyl-dependent dehydrogenase), which plays a key role in the Krebs cycle and oxidative phosphorylation. This gene is a tumor suppressor gene and its mutations cause 3P syndrome (acromegaly, heochromocytoma, paraganglioma). We also found mutations in the genes SDHC, CDKN1B unique to some patients from this sample. Conclusion. Three exon threatening and potentially harmful mutations were found in the genes CDKN1B and SHDB, which are detected in patients with endocrine syndromes

Background Vitamin D deficiency is a global health problem, it is assessed by measuring serum 25-hydroxivitamin D (25(OH) D), nevertheless epidemiological data for many countries remains underreported. Objectives To study the prevalence of vitamin D deficiency throughout the calendar year in a large cohort recruited ina multiethnic Transcarpathian region of Ukraine. Methods In this retrospective study 25(OH) D serum concentration was measured during all 12 months of the year 2019 by electrochemoluminescent assay on the automatic analyzer Cobas e411 in 1823 subjects, including both children and adults (1551 females (85.03%) and 273 males (14.97%)). Results The mean 25(OH) D concentration in adults demonstrates significantly lower levels compared to children (22.67 ± 8.63 ng/ml vs. 26.00 ± 10.72 ng/ml respectively, p ). Adult women expressed significantly lower mean annual serum 25 (OH) D concentrations in comparison to men (22.29 ± 8.46 ng/ml vs. 25.75 ± 9.38 ng/ml respectively, p ). In contrast, children did not show a significant difference between sexes (girls 24.98 ± 10.38 ng/ml vs. boys 27.01 ± 11.01 ng/ml, p = 0.2003). In the winter months, 25(OH) D levels fell below 20 ng/ml in 51,74% of adult population of Thranscarpathia, and in 12.91%, − below 12 ng/ml. Conclusions The results of this study contradict the previously reported evaluations of the vitamin D levels in Ukraine which were assessed by measuring serum 25(OH) D. Specifically, only approximately half of the studied population is vitamin D deficient during winter season. This study features the most representative sample size in Ukraine to date.

The main goal of this collaborative effort is to provide genome wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for the public data release. DNBSEQ-G50 sequences, and genotypes by an Illumina GWAS chip were cross-validated on multiple samples, and additionally referenced to one sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage. The genome data has been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, CNVs, SNPs and microsatellites. This study provides the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for historic and medical research in a large understudied population. While most of the common variation is shared with other European populations, this survey of population variation contributes a number of novel SNPs and structural variants that have not been reported in the gnomAD/1KG databases representing global distribution of genomic variation. These endemic variants will become a valuable resource for designing future population and clinical studies, help address questions about ancestry and admixture, and will fill a missing place in the puzzle characterizing human population diversity in Eastern Europe. Our results indicate that genetic diversity of the Ukrainian population is uniquely shaped by the evolutionary and demographic forces, and cannot be ignored in the future genetic and biomedical studies. This data will contribute a wealth of new information bringing forth different risk and/or protective alleles. The newly discovered low frequency and local variants can be added to the current genotyping arrays for genome wide association studies, clinical trials, and in genome assessment of proliferating cancer cells.

BackgroundThe main goal of this collaborative effort is to provide genome-wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for public data release. BGISEQ-500 sequence data and genotypes by an Illumina GWAS chip were cross-validated on multiple samples and additionally referenced to 1 sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage.ResultsThe genome data have been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, copy number variations, single-nucletide polymorphisms, and microsatellites. To our knowledge, this study provides the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for medical research in a large understudied population.ConclusionsOur results indicate that the genetic diversity of the Ukrainian population is uniquely shaped by evolutionary and demographic forces and cannot be ignored in future genetic and biomedical studies. These data will contribute a wealth of new information bringing forth a wealth of novel, endemic and medically related alleles.

Background: Vitamin D deficiency is a global health problem, it is assessed by measuring serum 25(OH)D, nevertheless epidemiological data for many countries remains underreported.Objectives: To study the prevalence of vitamin D deficiency throughout the calendar year in a large cohort recruited in a multiethnic Transcarpathian region of Ukraine.Methods: In this retrospective study 25(OH)D serum concentration was measured during all 12 months of the years 2019 by electrochemoluminescent assay “Elecsys Vitamin D total”, Roche® (Germany) on the automatic analyzer Cobas e411 in 1,823 subjects, including both children and adults (1551 females (85.03%) and 273 males (14.97%)).Results: Mean 25(OH) D concentration in adults shows significantly lower levels compared to children (22.67±8.63 ng/ml vs. 26.00±10.72 ng/ml respectively, p=0.00001). Adult women expressed significantly lower mean year serum 25(OH) D concentration in comparison to men (22.29±8.46 ng/ml vs. 25.75±9.38 ng/ml respectively, p= 0.0000003). On the other hand, children did not show a significant difference between sexes (girls 24.98±10.38 ng/ml vs. boys 27.01±11.01 ng/ml, p=0.2003). In the winter months, 25(OH)D levels fell below 20 ng/ml in 51,74 % of adult population of Thranscarpathia, and in 12.91%, - below 12 ng/ml.Conclusions: The results of this study contradict the previously reported evaluations of the vitamin D levels in Ukraine assessed by measuring serum 25(OH)D. Specifically, only around half of the studied population is vitamin D deficient during “low” winter season. This study features the most representative sample size in Ukraine to date.