Centromeres are essential for chromosome inheritance and genome stability. Centromeres are defined by repetitive DNA and centromeric proteins, including the centromeric histone centromere protein A (CENP-A), define the site of centromeric chromatin and kinetochore assembly. Neocentromeres are rare human chromosomal aberrations where a new centromere has formed in a previously non-centromeric location and there are new sites of assembly of functional kinetochores at ectopic loci. Evolutionary new centromeres are important steps in specification that involve centromere repositioning events that become fixed in the population. In this review the importance of neocentromeres to human health and chromosome evolution are discussed.

Quantitative analysis of DNA methylation patterns is an intrinsic part of epigenetic cancer research. Besides, detection of tumour specific epigenetic aberrations holds promise for cancer diagnostics. PCR amplification of loci of interest from bisulfite treated DNA is a common sample preparation step. Given the fact amplicons and not the genomic DNA is used for quantification of the methylation percentages, the PCR amplification step is limiting factor for the accuracy of the entire analysis. Preferential amplification of either methylated or unmethylated alleles may hamper the correct interpretation of results. Additional biases may be introduced by the quantification technologies on their own, for example the specificity of oligonucleotide probes of a microarray. Aim. The aim of present work was to evaluate the applicability of the cubic polynomial regression for correction of measurement biases in quantitative DNA methylation data that were obtained by the next generation sequencing and hybridisation analysis on the oligonucleotide microarrays. Materials and Methods. Next generation bisulfite 454 sequencing and hybridisation on the in situ synthesised microarrays (Febit Biotech) was employed to quantify DNA methylation in vicinity of the transcriptional start sites. Cubic polynomial regression was used to analyse the calibration data. Results. Candidate genes were selected that exhibit aberrant DNA methylation patterns in cancer. Specifically, these included genes coding for the subunits of succinate dehydrogenase ( SDH ) as well as tumour suppressor genes CDKN2B , DAPK1 and TP53 . The interrogated DNA loci were amplified from control DNA samples of defined methylation percentages. Substantial deviations of apparent methylation percentages from theoretically expected values were detected by the sequencing of SDHB and SDHD amplicons. Likewise, the methylation indices of the CDKN2B and DAPK1 CpG sites that were analysed were significantly biased in the microarray data. Correction of biased data was performed by using the equations of respective regression curves resulting in almost complete removal of the artefacts. Conclusions. Successful application of cubic polynomial regression was achieved for correcting measurement biases in two different types of quantitative DNA methylation data - namely next generation bisulfite sequencing and hybridisation on the oligonucleotide microarrays - demonstrating the universal applicability of this correction process.

Mathematics is acquiring ever greater significance in the modern society. Mathematics represents an everyday tool in physics, astronomy, biology, engineering, management and other fields of theoretical and applied activities. However, many people deliberately avoid choosing courses including mathematics operations. This observation might partly be explained by an increased mathematical anxiety (MA) manifested as a sense of high anxiety and awkwardness connected with difficulties in manipulations with numbers in both academic and everyday situations. The proteins encoded by contactin associated protein-like 2(CNTNAP2)and neurexin-1 genes (NRXN1) are involved in the regulation of synaptic plasticity representing one of the mechanisms of working memory and, hence, in resistance to stressful life events. The present study aimed to examine the role of NRXN1 (rs4971648, rs1045881) and CNTNAP2 (rs2710102, rs2530310) gene polymorphisms in math anxiety. The study involved 523 healthy individuals from Republic of Bashkortostan (75% women) (mean age 20.3 ± 3.87 years). MA level was assessed via Mathematics Anxiety Rating Scale- Elementary Form (MARS-E). SNPs genotyping was performed via PCR-RFLP. Statistical analysis was conducted with Plink v.1.07. According to the analysis of gene-environment interactions, individuals with the highest or lowest order of birth (b = -6.77; p = 0.021) and/or with less than one sibling (b = -10.37; P = 0.012) demonstrated an increased MA in the presence ofCNTNAP2 rs2530310 A-allele. Revealed findings evidence in modulating effect of environmental factors (i.e. «birth order» and «number of siblings in the family») in association of CNTNAP2 gene with individual variations in MA.

We report the results of comprehensive molecular genetic examination of patients with a clinical diagnosis of neurofibromatosis. To detect molecular genetic alterations characteristic for type 1 or type 2 neurofibromatosis we applied a set of new medical technologies, including tageted high-throughput parallel DNA sequencing (NGS) and multiplex ligation probe amplification (MLPA). Search for point mutations, small insertions / deletions / duplications in NF1 and NF2 genes was carried out with next generation sequencing on the Ion Torrent PGM. To identify extended deletions in NF1 and NF2 genes MLPA method was used. In a sample of 200 patients, mutations in NF1 and NF2 genes were detected in 48.5% of cases. MLPA technique has allowed us to identify deletions in the NF1 gene in 14 out of 100 patients tested. In case of detection of a mutation in a patient with neurofibromatosis, carrier status exclusion or confirmation in close relatives, and early diagnosis.

The results of researches made by the group of the leading geneticists from Federal State Budgetary Institution «Research Centre for Medical Genetics» and the experts of national consensus «Cystic Fibrosis: definition, diagnostic criteria, treatment» are presented. The decision about starting of the project was made on 6^th February 2013 at a meeting of the Scientific Council of the National social organization «All-Russian Association for patients with Cystic Fibrosis». Three consensus sections has been published already, this section (4) is one of the determinants in the diagnosis of cystic fibrosis and is the pharmacogenetic basis for targeted therapy for the disease. Consensus represents the generalized Russian and international experience in genetic diagnostics of cystic fibrosis, conditions associated with the CFTR . Modern classification of CFTR mutations and their clinical significance and approaches to the analysis of pathogenicity are described. Analysis of the diversity of the CFTR mutations in the Russian Federation based on the data from the National CF Patients Register for 2014 and the features of the frequencies of CFTR mutations in representatives of different nationalities is done. The Russian and foreign panels of the most common mutations and recommendations about the algorithm of DNA diagnostics are described. For the first time the information about prenatal and preimplantation diagnostics of the disease is presented. The unified requirements for the form of the genetic conclusion are described.

Relevance: Testing of hereditary predisposition to thrombosis is an actual topic in medical genetic counseling. Information about increased risk for clotting abnormalities is important for preventing pregnancy complications, deep venous thrombosis, thromboembolism and other life-threatening conditions. Aim: To develop set of oligonucleotide probes for multiplex genotyping of several polymorphisms in the genes influencing thrombosis risk, using SNaPshot minisequencing technique. Materials and methods: The list of polymorphisms consisted of rs6025, rs6027, rs 1800595 in F5 ; rs1799963 in F2 ; rs5918 in ITGB3. For selecting the probes and PCR primers, Vector NTI и Primer3 programs were used. Results: After picking up the probes, possibility of multiplexing the polymorphisms in one tube was confirmed by Primer Focus kit reaction. Then several DNA samples with known genotypes were genotyped using the probes. In all cases, the genotypes determined by SNaPshot method corresponded to the genotypes detected by other methods. Conclusions: Panel of oligonucleotide probes for multiplex genotyping of five polymorphisms in the genes for coagulation factors II and V, and for integrin beta-3 (rs1799963, rs6025, rs6027, rs1800595, rs5918), has been developed and verified. The method allows speeding up and automatization of the genotyping process.