To evaluate a possible role of a novel c.A212G substitution in the PUS3 gene at intellectual disability (ID). Methods. The observed group consisted of the ID Ukrainian family members (parents and two affected children) and the control group-of 300 healthy individuals from general population of Ukraine. Sanger sequencing of the PUS3 gene exon 1 was performed for the family members. Polymorphic variants of c.A212G were analyzed using ARMS PCR. The homology models of wild type and p.Y71C mutant catalytic domains of human Pus3 were generated using the crystal structure of the human Pus1 catalytic domain (PDB ID: 4NZ6) as a template. Results. It was shown that the father of the affected siblings was the c.A212G substitution heterozygous carrier whereas the mother was a wild type allele homozygote, and the exom sequencing result was confi rmed-the affected children are 212G homozygotes. We supposed de novo mutation in the maternal germ line. A low frequency of 212G allele (0.0017) was shown in the population of Ukraine. Homology modelling of the wild type and p.Y71C mutant catalytic domain of human Pus3 revealed that substitution p.Y71C is located in close proximity to its active site. Conclusions. The absence of hypoproteinemia in our patients, homozygous for the 212C allele allows us to assume that the mutation c.A212G PUS3 is rather neutral and cannot be the major cause of ID. However, considering a low frequency of the 212G allele in the population and close localization of p.Y71C substitution to the active site of hPus3 we cannot exclude that the c.A212G mutation in PUS3 may be a modifi er for some pathologies including syndromic ID.

To identify and characterize the SARS-CoV-2 variants, collected upon the new wave of COVID-19 outbreak in Ivano-Frankivs'k region of Ukraine, using the whole genome genotyping. Methods. The parallel whole genome sequencing was performed on the processed RNA, isolated from nasopharyngeal swabs of 19 patients, using an Ion GeneStudio S5 Plus System. Results. All the identified SARS-CoV-2 genotypes were referred to 20I/501Y.V1 clade, the variant VUI202012/01 GRY (the B.1.1.7 lineage). In the analyzed virus variants forty-seven various mutations were found. Besides the founder 20I/501Y.V1 missense mutations, several unique alterations were detected, including those in the S-and N-proteins of SARS-CoV-2, that might have clinical and epidemiological relevance. Conclusions. The current wave of the COVID-19 outbreak in Ukraine is associated not only with seasonal fluctuations in the virus transmission, but also with the emergence of more aggressive virulent variants, such as B.1.1.7, which basically displaced previous strains and affects the younger population.

Analysis the EPHA1 gene G1475A and G1891A alleles distribution in the population of Ukraine, and to study the protein secondary structure as the first step in the investigation of EPHA1 gene involvement in intellectual disability pathogenesis. Methods. Observation group consisted of 300 individuals, including 164 (54.6 %) male and 136 (45.3 %) female individuals. Polymorphic variants were detected using PCR followed by Kpn1 RFLP analysis for G1475A and ARMS PCR analysis for G1891A. Results. The data concerning EPHA1 genotypes and allelic variants distribution were obtained. The low frequency of 1475A allele (0,012) and the absence of 1891A allele (not previously described) were revealed in the population of Ukrainian. Conclusions. Assays for the detection of EPHA1 gene G1475A and G1891A SNPs based on ARMS and restriction analysis were developed and the preliminary data on distribution of G1475A and G1891A polymorphisms in the population of Ukraine were obtained.

We assessed the predictive ability of a combined genetic variant panel for the risk of recurrent pregnancy loss (RPL) through a case-control study. Our study sample was from Ukraine and included 114 cases with idiopathic RPL and 106 controls without any pregnancy losses/complications and with at least one healthy child. We genotyped variants within 12 genetic loci reflecting the main biological pathways involved in pregnancy maintenance: blood coagulation (F2, F5, F7, GP1A), hormonal regulation (ESR1, ADRB2), endometrium and placental function (ENOS, ACE), folate metabolism (MTHFR) and inflammatory response (IL6, IL8, IL10). We showed that a genetic risk score (GRS) calculated from the 12 variants was associated with an increased risk of RPL (odds ratio 1.56, 95% CI: 1.21, 2.04, p = 8.7 × 10−4). The receiver operator characteristic (ROC) analysis resulted in an area under the curve (AUC) of 0.64 (95% CI: 0.57, 0.72), indicating an improved ability of the GRS to classify women with and without RPL. Ιmplementation of the GRS approach can help define women at higher risk of complex multifactorial conditions such as RPL. Future well-powered genome-wide association studies will help in dissecting biological pathways previously unknown for RPL and further improve the identification of women with RPL susceptibility.

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