Although Slavic populations account for over 4.5% of world inhabitants, no centralised, open-source reference database of genetic variation of any Slavic population exists to date. Such data are crucial for clinical genetics, biomedical research, as well as archeological and historical studies. The Polish population, which is homogenous and sedentary in its nature but influenced by many migrations of the past, is unique and could serve as a genetic reference for the Slavic nations. In this study, we analysed whole genomes of 1222 Poles to identify and genotype a wide spectrum of genomic variation, such as small and structural variants, runs of homozygosity, mitochondrial haplogroups, and de novo variants. Common variant analyses showed that the Polish cohort is highly homogenous and shares ancestry with other European populations. In rare variant analyses, we identified 32 autosomal-recessive genes with significantly different frequencies of pathogenic alleles in the Polish population as compared to the non-Finish Europeans, including C2, TGM5, NUP93, C19orf12, and PROP1. The allele frequencies for small and structural variants, calculated for 1076 unrelated individuals, are released publicly as The Thousand Polish Genomes database, and will contribute to the worldwide genomic resources available to researchers and clinicians.

Background: Severe outcomes of COVID-19 account for up to 15% of all cases. The study aims to check if any gene variants related to cardiovascular (CVD) and pulmonary diseases (PD) are correlated with a severe outcome of COVID-19 in a Polish cohort of COVID-19 patients. Methods: In this study, a subset of 747 samples from unrelated individuals collected across Poland in 2020 and 2021 was used and whole-genome sequencing was performed. Results: The GWAS analysis of SNPs and short indels located in genes related to CVD identified one variant significant in COVID-19 severe outcome in the HADHA gene, while for the PD gene panel, we found two significant variants in the DRC1 gene. In this study, both potentially protective and risk variants were identified, of which variants in the HADHA gene deserve the most attention. Conclusions: This is the first study reporting the association between the HADHA and DRC1 genetic variants and COVID-19 severe outcome based on the cohort WGS analysis. Although all the identified variants are localised in introns, they may be correlated and therefore inherited along with other risk variants, potentially causative to severe outcome of COVID-19 but not discovered yet.

Introduction: Encephalopathy and stroke in COVID-19 patients have been repeatedly reported. Previous reports indicate that SARS-CoV-2 infection is associated with a significantly escalated risk of ischemic stroke, especially with potentially cryptogenic stroke. Encephalopathy is also present in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Definitive diagnosis of CADASIL is based on sequencing the NOTCH3 gene. Primary pathology is the accumulation of abnormal transmembrane deposits on vascular smooth muscle cells in the brain and other organs.Material and methods: Genome of the patient was sequenced with the average depth of coverage 32,7x and mapped to the reference genome GRCh38. The whole genome sequencing (WGS) approach identified heterozygous missense variant NOTCH3 in the exon 8. Targeted Sanger sequencing was done to confirm the presence of the variant, and to examine the closest relatives. Beside the patient, all family members were unaffected, the variant appeared de novo.Results: Identified variant was not reported in the GnomAD v.3 and 1000 Genomes, nor in polymorphism database dbSNP. No clinical information was available in ClinVar. The only information regarding variants in the same amino acid position (Cs440Ser and Cys440Gly) from LOVD database were reported by Markus et al. They were found in 2 individuals affected with CADASIL and interpreted as pathogenic on the basis of symptoms and familial cosegregation. Beside the patient, all family members were unaffected, the variant appeared de novo.Conclusions: The simultaneous COVID-19 infection could probably provoke an exacerbation of a previously asymptomatic CADASIL patient and could lead to an acute ischemic multi-infarct encephalopathy.