Transferability of the PRS estimates for height and BMI obtained from the European ethnic groups to the Western Russian populations.

Genetic data plays an increasingly important role in modern medicine. Decrease in the cost of sequencing with subsequent increase in imputation accuracy, and the accumulation of large amounts of high-quality genetic data enable the creation of polygenic risk scores (PRSs) to perform genotype-phenotype associations. The accuracy of phenotype prediction primarily depends on the overall trait heritability, Genome-wide association studies cohort size, and the similarity of genetic background between the base and the target cohort. Here we utilized 8,664 high coverage genomic samples collected across Russia by "Evogen", a Russian biomedical company, to evaluate the predictive power of PRSs based on summary statistics established on cohorts of European ancestry for basic phenotypic traits, namely height and BMI. We have demonstrated that the PRSs calculated for selected traits in three distinct Russian populations, recapitulate the predictive power from the original studies. This is evidence that GWAS summary statistics calculated on cohorts of European ancestry are transferable onto at least some ethnic groups in Russia.

Unified representation of high- and low-resolution spectra to facilitate application of mass spectrometric techniques in clinical practice.

The majority of research in the biomedical sciences is carried out with the highest resolution accessible to the scientist, but, in the clinic, cost constraints necessitate the use of low-resolution devices. Here, we compare high- and low-resolution direct mass spectrometry profiling data and propose a simple pre-processing technique that makes high-resolution data suitable for the development of classification and regression techniques applicable to low-resolution data, while retaining high accuracy of analysis. This work demonstrates an approach to de-noising spectra to make the same representation for both high- and low-resolution spectra. This approach uses noise threshold detection based on the Tversky index, which compares spectra with different resolutions, and minimizes the percentage of resolution-specific peaks. The presented method provides an avenue for the development of analytical algorithms using high-resolution mass spectrometry data, while applying these algorithms in the clinic using low-resolution mass spectrometers.

[The diagnosis of idiopathic epilepsy in children based on the algorithm of molecular-genetic studies]. / Diagnostika idiopaticheskikh form epilepsii u detei na osnovanii algoritma molekulyarno-geneticheskogo issledovaniya.

AIM: To study mutations and polymorphisms in the sodium channels genes, determining the development of idiopathic epilepsy (IE). MATERIAL AND METHODS: The study of SCN1A gene by direct Sanger sequencing in 53 patients and targeted resequencing of the regions of 34 genes in 40 patients with different clinical forms of IE was performed. RESULTS: Seven mutations (c.3022G>T, c.3637C>T, c.1144G>T, c.80G>C, c.1603C>T, c.2427G>A and c.1131A>C) were detected among 53 patients by direct Sanger sequencing of SCN1A gene. The mutations of SCN1A gene (2 - nonsense mutation, 5 - missense mutation) were identified in 7/40 (17.5%) patients with epilepsy using high-performance sequencing, Mutations in sodium channel genes encoding other subunits: SCN1B, SCN2A, SCN9A were identified in 6 patients. CONCLUSION: As epileptic encephalopathy is polygenic, it is important to conduct genetic testing of more genes (primarily sodium channel genes - SCN1B, SCN2A, SCN9A etc.) using special gene panels to find the molecular defect in DNA.

A new reliable reference gene UBA52 for quantitative real-time polymerase chain reaction studies in pyloric cecal tissues of the starfish Asterias rubens.

The starfish Asterias rubens is one of the most abundant echinoderm species in the White, Barents, North, and Baltic Seas. This species is an important component of marine ecosystems and a model object for certain biological studies, in particular those requiring quantitative estimation of gene expression. As a rule, expression at the transcriptional level is estimated by real-time qPCR using the ΔΔCt method, which allows the comparison of the copy number of target gene transcripts in samples with unknown mRNA/cDNA concentration. Application of this method requires normalization of the results relative to genes with stable expression levels (reference genes). The identification of reference genes is still a challenging task since data of this kind are missing for certain taxa, whereas the use of "standard" endogenous control genes without additional tests might lead to erroneous conclusions. We performed a preliminary analysis of the expression of many housekeeping genes in the pyloric ceca of A. rubens by high-throughput sequencing under normal and heat shock conditions. For one of them, the ubiquitin gene UBA52, low variation of expression (not greater than 2-fold) was shown using real-time qPCR. Tissues of pyloric ceca of normal adults and underyearlings and of adults after heat shock were used. The data obtained suggest that the UBA52 gene may be used as reference for normalization of gene expression at the mRNA level in the starfish A. rubens and probably in closely related species.

[Polymorphism of KPI-A genes from plants of the subgenus Potatoe (sect. Petota, Estolonifera and Lycopersicum) and subgenus Solanum].

Kunitz-type proteinase inhibitor proteins of group A (KPI-A) are involved in the protection of potato plants from pathogens and pests. Although sequences of large number of the KPI-A genes from different species of cultivated potato (Solanum tuberosum subsp. tuberosum) and a few genes from tomato (Solanum lycopersicum) are known to date, information about the allelic diversity of these genes in other species of the genus Solanum is lacking. In our work, the consensus sequences of the KPI-A genes were established in two species of subgenus Potatoe sect. Petota (Solanum tuberosum subsp. andigenum--5 genes and Solanum stoloniferum--2 genes) and in the subgenus Solanum (Solanum nigrum--5 genes) by amplification, cloning, sequencing and subsequent analysis. The determined sequences of KPI-A genes were 97-100% identical to known sequences of the cultivated potato of sect. Petota (cultivated potato Solanum tuberosum subsp. tuberosum) and sect. Etuberosum (S. palustre). The interspecific variability of these genes did not exceed the intraspecific variability for all studied species except Solanum lycopersicum. The distribution of highly variable and conserved sequences in the mature protein-encoding regions was uniform for all investigated KPI-A genes. However, our attempts to amplify the homologous genes using the same primers and the genomes of Solanum dulcamarum, Solanum lycopersicum and Mandragora officinarum resulted in no product formation. Phylogenetic analysis of KPI-A diversity showed that the sequences of the S. lycopersicum form independent cluster, whereas KPI-A of S. nigrum and species of sect. Etuberosum and sect. Petota are closely related and do not form species-specific subclasters. Although Solanum nigrum is resistant to all known races of economically one of the most important diseases of solanaceous plants oomycete Phytophthora infestans aminoacid sequences encoding by KPI-A genes from its genome have nearly or absolutely no differences to the same from genomes of cultivated potatoes involved by P. infestans.

[Increase in NETO2 gene expression is a potential molecular genetic marker in renal and lung cancers].

Multiple changes in the genome, transcriptome, and proteome are frequent in cancer cells. A search for molecular markers based on DNA, mRNA, or proteins is a main method to develop early specific diagnostics for cancer. While universal markers are still unavailable, similar trends are known for the expression patterns of particular genes in certain epithelial tumors. A bioinformatic screening of transcriptomic databases identified the NETO2 gene as a new potential promising marker of renal cancer. A substantial increase in NETO2 mRNA level was detected in 90% clear-cell renal cell carcinomas, 70% of non-small cell lung cancers, and 50% of papillary renal cancers by real-time PCR. The NETO2 mRNA level was increased to a lesser extent in cervical carcinoma and colon cancer and tended to decrease in cancer of the stomach. The NETO2 gene, which codes for a membrane glycoprotein with an unclear function, was assumed to provide a new promising marker for early diagnosis in renal cancer and non-small cell lung cancer.

ATP as effector of inorganic pyrophosphatase of Escherichia coli. Identification of the binding site for ATP.

The interaction of Escherichia coli inorganic pyrophosphatase (E-PPase) with effector ATP has been studied. The E-PPase has been chemically modified with the dialdehyde derivative of ATP. It has been established that in the experiment only one molecule of effector ATP is bound to each subunit of the hexameric enzyme. Tryptic digestion of the adenylated protein followed by isolation of a modified peptide by HPLC and its mass-spectrometric identification has showed that it is an amino group of Lys146 that undergoes modification. Molecular docking of ATP to E-PPase indicates that the binding site for effector ATP is located in a cluster of positively charged amino acid residues proposed earlier on the basis of site-directed mutagenesis to participate in binding of effector pyrophosphate. Molecular docking also reveals several other amino acid residues probably involved in the interaction with effectors.