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Abstract Background Kazakhstan remains a high-burden TB prevalence country with a concomitent high-burden of multi-drug resistant tuberculosis. For this reason, we performed an in depth genetic diversity and population structure characterization of Mycobacterium tuberculosis complex (MTC) genetic diversity in Kazakhstan with both patient and community benefit. Methods A convenience sample of 700 MTC DNA cultures extracts from 630 tuberculosis patients recruited from 12 out of 14 regions in Kazakhstan, between 2010 and 2015, was independently studied by high-throughput hybridization-based methods, TB-SPRINT (59-Plex, n = 700), TB-SNPID (50-Plex, n = 543). DNA from 391 clinical isolates was successfully typed by two methods. To resolve the population structure of drug-resistant clades in more detail two complementary assays were run on the L2 isolates: an IS6110-NTF insertion site typing assay and a SigE SNP polymorphism assay. Results Strains belonged to L2/Beijing and L4/Euro-American sublineages; L2/Beijing prevalence totaled almost 80%. 50% of all samples were resistant to RIF and to INH., Subtyping showed that: (1) all L2/Beijing were “modern” Beijing and (2) most of these belonged to the previously described 94–32 sublineage (Central Asian/Russian), (3) at least two populations of the Central Asian/Russian sublineages are circulating in Kazakhstan, with different evolutionary dynamics. Conclusions For the first time, the global genetic diversity and population structure of M. tuberculosis genotypes circulating in Kazakhstan was obtained and compared to previous local studies. Results suggest a region-specific spread of a very limited number of L2/Beijing clonal complexes in Kazakhstan many strongly associated with an MDR phenotype.

This study explores an adaptation mechanism of Bacteroides fragilis to subinhibitory concentrations of meropenem, characterized by an alteration in the production of membrane vesicles (MVs) and modulation of the host inflammatory response. Using a rat model of infection, we demonstrated a significant increase in the size of MVs accompanied by a nonsignificant increase in their number in the meropenem-treated group compared to the infected control. Both infected groups showed significantly altered hematological parameters and shifts in monocyte on day 8 (average increase of 21.5 %). At the same time, significant changes in neutrophils (decrease by 26 %) and eosinophils (increase by 3 %) were observed only in the infected group but not in the infected meropenem-treated group. On day 16, increased macrophage activation, neovascularization, and fibrosis were observed in the tissues of the antibiotic-treated group. Immunological profile analysis revealed a slight increase in the levels of pro-inflammatory cytokines (IL-5, IL-6, IFN-γ and G-CSF) on day 8 of the experiment, followed by a sharp decrease on day 16 in both infected groups compared to the negative control. At the same time, network analysis of correlations between these immunological factors showed complex changes in response to subinhibitory concentrations of meropenem. The bacterial load did not differ between the infected groups on days 8 and 16, but only in the meropenem-free group a significant decrease in the number of bacteria was observed on day 16 in all samples. These findings suggest that subinhibitory antibiotic concentrations can influence the pathophysiological progression of B. fragilis infection, modulating both the bacterial response and the host immune reaction, potentially leading to a more complex and chronic disease course., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: The prevalence of Bacteroides fragilis isolates resistant to first-line beta-lactam drugs is increasing, resulting in reduced treatment efficacy. Investigating the bacterial transcriptome and proteome can uncover links between bacterial genes and resistance mechanisms. In this study, we experimentally assessed in vitro the transcriptional and proteomic profiles of B. fragilis exposed to SICs of meropenem, an effective antimicrobial agent, collected from patients with intra-abdominal diseases at Astana City Hospital, Kazakhstan., Methods: B. fragilis was cultured in brain heart infusion broth and sub-cultured every 48 h for 8 days in media with and without meropenem. Total RNA was extracted from the liquid cultures using a commercial RNeasy mini kit, and strand-specific RNA sequencing (RNA-seq) was performed on the DNBSEQ platform. Raw RNA-seq data were retrieved from BioProject No. PRJNA531645 and uploaded to the NCBI Sequence Read Archive (accession no. SRX22081155). Proteins of B. fragilis were extracted and separated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis, followed by analysis of the eluted peptides using liquid chromatography-tandem mass spectrometry. Cluster analysis utilised the Database for Annotation, Visualisation, and Integrated Discovery., Results: The subinhibitory concentration (SIC) of meropenem was determined to be 0.5 μg/L (minimum inhibitory concentration: 1). Mapping of reads to the reference genome identified 2477 expressed genes in all B. fragilis BFR KZ01 samples. Ten differentially expressed genes (DEGs) were common across comparison groups during and post-antibiotic exposure (wMEM vs. MEM2 and MEM2 vs. rMEM8); however, no substantially enriched Gene Ontology terms were identified. The cluster analysis highlighted a significant enrichment cluster (W-0560 oxidoreductase) of DEGs following antibiotic withdrawal. In total, 859  B. fragilis proteins were identified, with the expressions of three proteins, 3-oxoacyl-[acyl carrier protein] reductase, acetyl-CoA carboxylase biotin carboxylase subunit, and beta-ketoacyl-ACP synthase III, being upregulated in the enriched protein folding category. Notably, chaperone proteins such as FKBP-type peptidyl-prolyl cis-trans isomerases (involved in the cis-trans isomerisation of prolyl peptide bonds) and GroES (a co-chaperone functioning with GroEL) were also identified., Conclusions: Under the influence of low doses of antibiotics defense mechanisms are activated which contribute to the emergence of resistance. These results provide insight into the response of B. fragili s to meropenem exposure, mainly at the SIC, contributing to the understanding bacterial survival strategies under stress conditions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Allelic variants of genes encoding enzymes of the esterase system ( CES1 ) and P-glycoprotein ( ABCB1 ) can change the metabolism and pharmacokinetics of dabigatran. Therefore, they act as determining factors in the development of side effects, especially bleeding. We analyzed the genotype-phenotype relationship of ABCB1 (rs1045642, rs4148738, rs2032582, and rs1128503) and CES1 (rs8192935, rs71647871, and rs2244613) polymorphisms in patients with atrial fibrillation who had been treated with dabigatran., Methods: A total of 150 patients were recruited for this study. TaqMan technology was used for SNP genotyping., Results: Patients with the rs2244613 GG genotype had a lower concentration (55.27 ± 34.22 ng/ml) compared to those with the TT genotype (63.33 ± 52.25 ng/ml) (additive model, P = 0.000). Individuals with the rs8192935 AA genotype had a lower concentration (52.72 ± 30.45 ng/ml) compared to those with the GG genotype (79.78 ± 57 ng/ml) (additive model, P = 0.001). The APTT values among the different genotypes of the ABCB1 SNPs, rs4148738 and rs1045642, were significantly different (P = 0.035 and P = 0.024, respectively)., Conclusion: Our research demonstrates that the CES1 polymorphisms, rs8192935 and rs2244613, are associated with the pharmacodynamics and pharmacokinetics of dabigatran in the Kazakh subpopulation., Competing Interests: The authors declare no conflict of interest., (© The Author(s).)

Type 2 diabetes mellitus (T2DM) is a socially significant disease with increasing prevalence worldwide. It is characterized by heterogeneous metabolic disorders and is associated with various risk factors, including BMI, abnormal lipid levels, hypertension, smoking, dietary preferences, physical inactivity, sedentary lifestyle, family history of diabetes, prediabetes or gestational diabetes, inflammation, intrauterine environment, age, sex, ethnicity, and socioeconomic status. Assessing the genetic risk of developing T2DM in specific populations remains relevant. The ADIPOQ gene, encoding adiponectin, is directly related to the risk of developing T2DM, obesity, and cardiovascular diseases. Our study demonstrated significant associations of ADIPOQ gene polymorphisms with the risk of developing T2DM and obesity, as well as with fasting glucose levels and BMI, in the Kazakh population. Specifically, rs266729 was significantly associated with T2DM and obesity in the Kazakh population, while other studied polymorphisms (rs1501299, rs2241766, and rs17846866) did not show a significant association. These findings suggest that ADIPOQ gene polymorphisms may influence T2DM risk factors and highlight the importance of genetic factors in T2DM development. However, further research in larger cohorts is needed to confirm these associations.

Background: Arteriovenous malformations (AVMs) are abnormal tangles of arteries and veins that connect directly without an intervening capillary bed. Epileptic seizures are the second most common symptom in patients with brain AVMs, occurring in 30 to 50% of cases. However, the exact mechanism of epileptic seizure development in AVMs remains unclear. In this study, we aimed to investigate the factors associated with epileptic seizures in patients with brain arteriovenous malformation (AVMs) in Kazakhstan., Methods: A case-control study was conducted, which included 163 patients diagnosed with brain AVMs. Demographic and clinical data were collected and analyzed, and multivariate logistic regression was built to assess the factors associated with seizures in brain AVMs., Results: from this rupture of vessels OR = 0.36 95% CI (0.14-0.91, a medium-to-high Spetzler-Martin score (III-V) OR = 6.16 (2.14-17.69) and OR = 3.05 (1.08-8.68), respectively), location in brain cortex (frontal lobe OR = 6.16 (2.04-18.54), parietal lobe OR = 9.37 (3.26-26.91), temporal lobe OR = 4.57 (1.56-13.36), occipital lobe OR = 0.27 (0.08-0.91), and the presence of hemiparesis OR = 0.12 (0.02-0.66) in adverse outcomes were statistically significantly associated with the presence of epileptic seizures in brain arteriovenous malformations patients., Conclusions: To conclude, this contributed to model factors associated with brain arteriovenous malformations that are linked to epileptic seizures.

Background: A vein of Galen aneurysmal malformation (VGAM) is a rare congenital cerebral vascular condition with a high mortality rate if left untreated. This study describes the long-term outcomes of patients with VGAM, who were treated with endovascular embolization., Methods: This retrospective analysis focused on VGAM patients who underwent one or more endovascular embolization sessions between January 2008 and December 2022. The study included newborns and children under 18 years. Data encompassed clinical and demographic characteristics, types of endovascular embolization, treatment complications, mortality rates, and long-term outcomes., Results: Out of 22 VGAM cases, the majority were boys (86.36%), and the average age of the participants was 38 months, ranging from 25 days to 17 years. Endovascular embolization using liquid embolizing agents was the most common intervention (50%), and around 73% of patients underwent multiple sessions. Some patients underwent ventriculoperitoneal shunting (VPS) due to persistent hydrocephalus. In long-term outcomes, four patients (18.2%) showed developmental delays, and 16 patients (72.7%) had a positive outcome., Conclusions: Combining endovascular therapy with a comprehensive management strategy significantly reduces mortality rates and improves the possibility of normal neurological development in patients.

Background: Seizures are one of the most debilitating manifestations of brain arteriovenous malformations (AVMs). This study aimed to evaluate the effect of curative embolization on brain AVM patients presenting with seizures., Methods: The records of patients who underwent embolization for brain AVM from January 2012 to December 2020 were evaluated and patients presenting with seizures were interviewed. Patient responses were evaluated according to the International League Against Epilepsy (ILAE) and Engel classifications. Statistical analyses of factors associated with seizure outcomes and complications were performed using ANOVA and Fischer's exact tests., Results: The mean age of the participants was 35.2 ± 10.7 years. More than 80% of the patients received no or suboptimal dosages of antiepileptic drugs (AEDs) prior to embolization. Positive seizure dynamics were observed in 50% of the patients post-procedure. A correlation was found between length of seizures in anamnesis and outcomes of both Engel and ILAE score, where shorter length was associated with better outcomes. Post-embolization hemorrhage was associated with initial presentation with hemorrhage., Conclusions: The embolization of brain AVMs had a positive effect on seizure presentation and a relatively low prevalence of complications. However, the results of the study are obscured by inadequate AED treatment received by the patients, which prompts prospective studies on the topic with careful patient selection.

An arteriovenous malformation (AVM) is an abnormal nidus of blood vessels that is characterized by a direct connection between arteries and veins without intervening in the capillary network. The exact underlying cause of sporadic AVMs is unknown, but many studies have reported genetic associations between genes that contribute to angiogenesis, vasculogenesis, and inflammation. Eleven studies retrieved from Medline Complete, PubMed, and Google Scholar up to February 2022 were included. Heterogeneity was assessed using I 2 and Q-tests. Publication bias was also assessed for the shortlisted CDKN2B-AS1 rs1333040 (T > C), ACVRL1 rs2071219 (A > G), and rs11169953 (C > T) polymorphisms. The rs1333040 polymorphism showed a lower association with sporadic brain AVM for T versus C in an allelic model (OR = 0.59, 95% confidence interval [CI] = 0.41-0.84). In the recessive model, rs2071219 for AA + AG vs. GG was OR = 0.62, 95% CI = 0.43-0.9. In the recessive model, rs11169953 CC + CT vs. TT was OR = 0.56, 95% CI = 0.33-0.95. In summary, the results of this study support the association between CDKN2B-AS1 and ACVRL1 polymorphisms and sporadic brain arteriovenous malformations. This study summarized the existing information and showed the need for more replication studies on the genetic basis of sporadic AVM. In the future, more genome-wide studies should be conducted to validate and fill existing gaps in knowledge about the mechanisms of sporadic AVM development., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rupture of intracranial aneurysms (IAs) is the most common cause of subarachnoid hemorrhage (SAH). Currently, there is sufficient evidence to indicate that inflammatory responses contribute to aneurysm rupture. Moreover, the familial occurrence of SAH suggests that genetic factors may be involved in disease susceptibility. In the present study, a clinically proven case of IA in a patient who is a heterozygous mutation carrier of the activated leukocyte cell adhesion molecule ( ALCAM )/cluster of differentiation 166 (CD166) gene, is reported. Genomic DNA was extracted from two siblings diagnosed with SAH and other available family members. A variant prioritization strategy that focused on functional prediction, frequency, predicted pathogenicity, and segregation within the family was employed. Sanger sequencing was also performed on the unaffected relatives to assess the segregation of variants within the phenotype. The verified mutations were sequenced in 145 ethnicity-matched healthy individuals. Based on whole exome sequencing data obtained from three individuals, two of whom were diagnosed with IAs, the single-nucleotide variant rs10933819 was prioritized in the family. Only one variant, rs10933819 (G>A), in ALCAM co-segregated with the phenotype, and this mutation was absent in ethnicity-matched healthy individuals. Collectively, ALCAM c1382 G>A p.Gly229Val was identified, for the first time, as a pathogenic mutation in this IA pedigree., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Aitkulova et al.)

Objectives: Bacteroides fragilis is one of the most important human anaerobic pathogens often found in various clinical infections. The purpose of this study was to determine the susceptibility of a B. fragilis clinical strain (BFR_KZ01) from Kazakhstan to the most commonly used anti-anaerobic drugs at the local level and to detect genes associated with resistance to these antibiotics., Methods: Species identification of the bacterial isolate was performed by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS) and 16S rRNA gene sequencing. Susceptibility to broad-spectrum antibiotics (metronidazole, meropenem, ciprofloxacin, clindamycin and tetracycline) most commonly used for the treatment of intra-abdominal infections (IAIs) was determined. Mass spectra groups essential for identifying cfiA-positive strains among clinical isolates were studied using ClinProTools 3.0.22 software. An Ion Torrent PGM™ platform was used for whole-genome sequencing (WGS) of the studied isolate., Results: The resulting WGS data of strain BFR_KZ01 was submitted to GenBank. In total, 5300 coding sequences (CDSs) and 69 RNA genes were determined. Analysis of the whole-genome data revealed that the studied strain harbours cfiA, nimB, tetQ and gyrA genes conferring resistance to key drugs used in treatment of the IAIs. MALDI-TOF/MS analysis assigned strain BFR_KZ01 to Group II (cfiA-positive); however, BFR_KZ01 was phenotypically sensitive to meropenem (mean MIC, 1.3 mg/L)., Conclusion: Determinants of drug resistance in strain BFR_KZ01 were identified. It was revealed that B. fragilis strain BFR_KZ01 from Kazakhstan is multidrug-resistant since it carries nimB, tetQ and gyrA genes conferring resistance to metronidazole, tetracycline and ciprofloxacin., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Our aim was to study the nucleotide sequences of 9 previously undescribed strains of B. fragilis collected from patients with intra-abdominal diseases at city hospitals in Nur-Sultan, Kazakhstan., (Copyright © 2021 Zholdybayeva et al.)

Background: The majority of the Kazakhs from South Kazakhstan belongs to the 12 clans of the Senior Zhuz. According to traditional genealogy, nine of these clans have a common ancestor and constitute the Uissun tribe. There are three main hypotheses of the clans' origin, namely, origin from early Wusuns, from Niru'un Mongols, or from Darligin Mongols. We genotyped 490 samples of South Kazakhs by 35 Y-chromosomal SNPs (single nucleotide polymorphism) and 17 STRs (short tandem repeat). Additionally, 133 samples from citizen science projects were included into the study., Results: We found that three Uissun clans have unique Y-chromosomal profiles, but the remaining six Uissun clans and one non-Uissun clan share a common paternal gene pool. They share a high frequency (> 40%) of the C2*-ST haplogroup (marked by the SNP F3796), which is associated with the early Niru'un Mongols. Phylogenetic analysis of this haplogroup carried out on 743 individuals from 25 populations of Eurasia has revealed a set of haplotype clusters, three of which contain the Uissun haplotypes. The demographic expansion of these clusters dates back to the 13-fourteenth century, coinciding with the time of the Uissun's ancestor Maiky-biy known from historical sources. In addition, it coincides with the expansion period of the Mongol Empire in the Late Middle Ages. A comparison of the results with published aDNA (ancient deoxyribonucleic acid) data and modern Y haplogroups frequencies suggest an origin of Uissuns from Niru'un Mongols rather than from Wusuns or Darligin Mongols., Conclusions: The Y-chromosomal variation in South Kazakh clans indicates their common origin in 13th-14th centuries AD, in agreement with the traditional genealogy. Though genetically there were at least three ancestral lineages instead of the traditional single ancestor. The majority of the Y-chromosomal lineages of South Kazakhstan was brought by the migration of the population related to the medieval Niru'un Mongols.

Here, we report the draft genome sequence of Bacteroides fragilis strain KZ02, isolated from a patient with peritonitis hospitalized in a health facility in Nur-Sultan, Kazakhstan. The genome of the strain contains 4,103 protein-coding genes, including the cepA gene, which causes resistance to beta-lactam antibiotics., (Copyright © 2020 Zholdybayeva et al.)

Background: LRRK2 mutations have emerged as the most prevalent and potentially treatable determinants of Parkinson's disease (PD). Peculiar geographic distribution of these mutations has triggered an interest in genotyping PD cohorts of different ethnic backgrounds for LRRK., Objective: Here, we report on the results of LRRK2 screening in the first Central Asian PD cohort., Methods: 246 PD patients were consecutively recruited by movement disorder specialists from four medical centers in Kazakhstan, and clinicodemographic data and genomic DNA from blood were systematically obtained and shipped to the Institute of Neurology University College London together with DNAs from 200 healthy controls. The cohort was genotyped for five LRRK2 mutations (p.Gly2019Ser, p.Arg1441His, p.Tyr1699Cys, p.Ile2020Thr, and p.Asn1437His) and three East Asian disease-associated variants (p.Gly2385Arg, p.Ala419Val, and p.Arg1628Pro) via Kompetitive allele-specific polymerase chain reaction assay analysis., Results: None of the study subjects carried LRRK2 mutations, whereas the following Asian variants were found with insignificant odds ratios (OR): p.Gly2385Arg (1.2%, minor allele frequency (MAF) 0.007, OR 1.25, p =0.8), p.Ala419Val (3.7%, MAF 0.02, OR 1.5, p =0.8), p.Ala419Val (3.7%, MAF 0.02, OR 1.5., Conclusions: We showed that East Asian LRRK variants could be found in Central Asian populations but their pathogenicity remains to be elucidated in larger PD cohorts., Competing Interests: The authors have no conflicts of interest., (Copyright © 2020 Rauan Kaiyrzhanov et al.)

Background: Kazakhstan remains a high-burden TB prevalence country with a concomitent high-burden of multi-drug resistant tuberculosis. For this reason, we performed an in depth genetic diversity and population structure characterization of Mycobacterium tuberculosis complex (MTC) genetic diversity in Kazakhstan with both patient and community benefit., Methods: A convenience sample of 700 MTC DNA cultures extracts from 630 tuberculosis patients recruited from 12 out of 14 regions in Kazakhstan, between 2010 and 2015, was independently studied by high-throughput hybridization-based methods, TB-SPRINT (59-Plex, n = 700), TB-SNPID (50-Plex, n = 543). DNA from 391 clinical isolates was successfully typed by two methods. To resolve the population structure of drug-resistant clades in more detail two complementary assays were run on the L2 isolates: an IS6110-NTF insertion site typing assay and a SigE SNP polymorphism assay., Results: Strains belonged to L2/Beijing and L4/Euro-American sublineages; L2/Beijing prevalence totaled almost 80%. 50% of all samples were resistant to RIF and to INH., Subtyping showed that: (1) all L2/Beijing were "modern" Beijing and (2) most of these belonged to the previously described 94-32 sublineage (Central Asian/Russian), (3) at least two populations of the Central Asian/Russian sublineages are circulating in Kazakhstan, with different evolutionary dynamics., Conclusions: For the first time, the global genetic diversity and population structure of M. tuberculosis genotypes circulating in Kazakhstan was obtained and compared to previous local studies. Results suggest a region-specific spread of a very limited number of L2/Beijing clonal complexes in Kazakhstan many strongly associated with an MDR phenotype.

Several diagnostic tests are being developed to detect drug resistance in tuberculosis. In line with previous developments detecting rifampicin and isoniazid resistance using microbead-based systems (spoligoriftyping and TB-SPRINT), we present here an assay called TB-EFI detecting mutations involved in resistance to ethambutol, fluoroquinolones and the three classical injectable drugs (kanamycin, amikacin and capreomycin) in Mycobacterium tuberculosis. The proposed test includes both wild-type and mutant probes for each targeted locus. Basic analysis can be performed manually. An upgraded interpretation is made available in Excel 2016®. Using a reference set of 61 DNA extracts, we show that TB-EFI provides perfect concordance with pyrosequencing. Concordance between genotypic resistance and phenotypic DST was relatively good (72 to 98% concordance), with lower efficiency for fluoroquinolones and ethambutol due to some untargeted mutations. When compared to phenotypical resistance, performances were similar to those obtained with Hain MTBDRsl assay, possibly thanks to the use of automatized processing of data although some mutations involved in fluoroquinolone resistance could not be included. When applied on three uncharacterized sets, phenotype could be predicted for 51% to 98% depending on the setting and the drug investigated, detecting one extensively drug-resistant isolate in each of a Pakistan and a Brazilian set of 91 samples, and 9 XDR among 43 multi-resistant Kazakhstan samples. By allowing high-throughput detection of second-line drugs resistance and of resistance to ethambutol that is often combined to second-line treatments, TB-EFI is a cost-effective assay for large-scale worldwide surveillance of resistant tuberculosis and XDR-TB control., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: ABO blood group genotyping is a new technology in hematology that helps prevent adverse transfusion reactions in patients. Identification of antigens on the surface of red blood cells is based on serology; however, genotyping employs a different strategy and is aimed directly at genes that determine the surface proteins. ABO blood group genotyping by real-time PCR has several crucial advantages over other PCR-based techniques, such as high rapidity and reliability of analysis. The purpose of this study was to examine nucleotide substitutions differences by blood types using a PCR-based method on Kazakh blood donors., Methods: The study was approved by the Ethics Committee of the National Center for Biotechnology. Venous blood samples from 369 healthy Kazakh blood donors, whose blood types had been determined by serological methods, were collected after obtaining informed consent. The phenotypes of the samples included blood group A (n = 99), B (n = 93), O (n = 132), and AB (n = 45). Genomic DNA was extracted using a salting-out method. PCR products of ABO gene were sequenced on an ABI 3730xl DNA analyzer (Applied Biosystems). The resulting nucleotide sequences were compared and aligned against reference sequence NM_020469.2. Real-time PCR analysis was performed on CFX96 Touch™ Real-Time PCR Detection System (BioRad)., Results: Direct sequencing of ABO gene in 369 samples revealed that the vast majority of nucleotide substitutions that change the ABO phenotype were limited to exons 6 and 7 of the ABO gene at positions 261, 467, 657, 796, 803, 930 and 1,060. However, genotyping of only three of them (261, 796 and 803) resulted in identification of major ABO genotypes in the Kazakh population. As a result, TaqMan probe based real-time PCR assay for the specific detection of genotypes 261, 796 and 803 was developed. The assay did not take into account several other mutations that may affect the determination of blood group, because they have a low occurrence rate and therefore have not been found in the population sample., Conclusion: Real-time PCR based method for fast and reliable ABO genotyping was developed. This assay may be used as a complement to classic serological blood typing.

Introduction: Single nucleotide polymorphism (SNP) at the collagen type I alpha 1 gene (COL1A1) rs1800012 has been widely studied and has shown an association with bone mineral density (BMD) and fractures. A minor allele TT of this SNP was found to be greatly overrepresented in individuals with fractures compared to controls, thus becoming a good predictor of increased fracture risk. The aim of this investigation was to evaluate potential association between COL1A1 gene polymorphism and osteoporosis in Kazakh postmenopausal women., Methods: The study population included 103 postmenopausal women recruited from Pavlodar and Almaty clinics. BMD was measured using DEXA. Genomic DNA was extracted from peripheral venous blood of study participants with Wizard® Genomic DNA Purification Kit (Promega, USA). Detection of COL1A1 +1245G/T (Sp1) polymorphism was done by the TaqMan® SNP Genotyping Assay of real-time PCR., Results: Densitometry results revealed 36 osteoporotic, 42 osteopenic, and 25 normal postmenopausal women. Data analysis of 1245G>T polymorphism in COL1A1 gene in the group of women with osteopenia and osteoporosis revealed deviation from Hardy-Weinberg equilibrium. The mutant TT genotype was prevalent compared to the heterozygous genotype GT in both groups. Distributions were 83% GG, 3% GT, and 14% TT in the group with osteopenia and 80% GG, 6% GT, and 14% TT in the group with osteoporosis. The distribution of genotypes frequency in the group of normal postmenopausal women was 76% GG, 16% GT, and 8% TT., Conclusion: These results suggest that TT genotype of COL1A1 +1245G/T (Sp1) polymorphism is associated with risk of postmenopausal osteoporosis in Kazakh women. Further studies involving a larger number of women are needed to clarify the relationship of this polymorphism with risk of osteoporosis.

A total of 60 Mycobacterium tuberculosis isolates collected from patients in prisons in Kazakhstan and 125 from the civilian sector were examined using mycobacterial interspersed repetitive units-variable number of tandem repeat analysis in 2012. The proportion of tuberculosis strains with unique genotypes isolated from the civilian patients was 50.4%, while that in the prison patients was 31.7%. This difference was statistically significant (χ(2) 4.42, P 0.035), and may reflect a low genetic diversity of M. tuberculosis strains isolated from prison patients. The frequencies of mutations in the rpoB531 and katG315 genes of the M. tuberculosis strains isolated from the civilians and in the penitentiary system were not significantly different (rpoB531: 82.4% vs. 88.3%, and katG315: 98.4% vs. 100%, respectively).

Introduction: Osteoporosis is a common age-related disease that is strongly influenced by genetics. Polymorphisms of the estrogen receptor gene alpha (ESR1) are consistently been associated with bone mineral density (BMD) and fracture.The purpose of this investigation was to evaluate potential association of single nucleotide polymorphism (SNP) variants of the ESR1 gene and bone mineral density (BMD) of the lumbar spine in Kazakh women., Methods: 140 female participants in Pavlodar clinics with varying measures of BMD. We are examined the potential association of BMD with 2 SNPs from the ESR1 gene (rs2234693 [PvuII] and rs9340799 [XbaI]). Genotyping of the PvuII and XbaI polymorphisms was performed by direct sequencing of the gene fragments containing restriction sites with the identification of genotypes PP, Pp, pp and XX, Xx, xx respectively., Results: Unadjusted mean BMD values ranged from 1.14±0.14 g/cm 2 in Caucasian women and 1.03±0.11 g/cm 2 in Asian women. The association between PvuII polymorphism and BMD at the lumbar spine (p= 0.04 for PP=Pp=pp) was statistically significant in all women. The XbaI polymorphism was not associated with BMD at lumbar spine. The relative risk for low BMD was higher for the marker PvuII (RR=1.51) than for the marker XbaI (RR=1.35)., Conclusion: The PvuII polymorphism had a weak association with lumbar spine BMD. XbaI polymorphism was unlikely to be a predictor of lumbar spine BMD in Kazakh women. These conclusions could help to determine the genetic risk factors for osteoporosis; however, further studies on the association between gene polymorphisms and BMD are needed including larger numbers of participants and genes to clarify genetic risks.

Introduction: Pharmacogenomics is an emerging field of medicine that combines genetics and pharmacology. Pharmacogenomic research is relatively new in Kazahkstan, but, in recent years, significant progress has been made in this field. The National Scientific Laboratory for Biotechnology has launched several government-funded research projects focused on finding genetic markers that determine susceptibility to various drugs. Another goal of pharmacogenetic research in the laboratory is to find the pharmacogenomic markers that target cardiovascular diseases, accounting for allelic frequencies in selected genes in the Kazakh population. In addition, pharmacogenomic testing kits allow patients to choose the drug dosage. For example, the drug Warfarin has been developed within the framework of the "Technology Commercialization Project," funded jointly by the Ministry of Education and Science of the Republic of Kazakhstan and the World Bank., Material and Methods: The pharmacogenomic studies were conducted using the real-time PCR and direct DNA sequencing. DNA was isolated from venous blood or buccal cells, collected from patients., Results: To date, we have identified the most promising areas of research in the field of pharmacogenomics in Kazakhstan. The allelic frequencies of a number of polymorphisms in the Kazakh population have been calculated (CYP2C9, CYP2C19, CYP3A4, VKORC1, CYP4F2, GGCX, CYP2D6, CYP1A2, NAT2, GSTP1, SLC47A1). A unique repository of DNA samples was established and is being replenished during the implementation of aforementioned projects. Development of the testing kit for individual selection of Warfarin dosage is nearing completion. A patent, named "Method of Selection Based Dose Warfarin Genotyping for the Kazakh Population" has been recently obtained. An application for another patent, titled "Express Method of Correction of Warfarin Dosing, Based on Real-time PCR" has received positive evaluation. The results of domestic pharmacogenomic studies will allow a more rational selection of drugs and their dosage regimens specific to the Kazakh population.

Introduction: Phase II xenobiotic biotransformation enzymes perform detoxification of hydrophilic and often toxic Phase I products through glutathionetransferase (GST), UDP-glucuronosyltransferase (UDF), N-acetyltransferase (NAT) families and other enzymes. GST protein families metabolize a large number of electrophilic xenobiotics, by conjugating fusing them with glutathione. Arylamine-N-acetyltransferase (NAT) catalyzes the acetylation of the aromatic and heterocyclic amines., Materials and Methods: This study assesses the frequency of NAT2 and GSTP1 gene polymorphisms in 326 healthy individuals from different regions of Kazakhstan by using Real-Time PCR and direct sequencing methods., Results: The allele frequencies were calculated for NAT2*5 (0.54) and GSTP1 (0.27). GSTP1 alleles were in the Hardy-Weinberg equilibrium (p > 0.05), while NAT2*5 (p = 0.00) were not. The population differences between North, Northeast and South Kazakhstan regions were also analyzed. No statistically significant differences in the frequency of genotypes were found., Conclusion: Allelic polymorphisms of NAT2*5 and GSTP1 genes greatly varied indifferent populations. The Kazakh population was significantly different from the Asian, Caucasoid, African-American and Hispanic populations by NAT2*5 and GSTP1 genes. Allelic variants of the NAT2*5 had a low frequency in Asian populations. Allelic frequency in other world populations varied from 30 to 50%. The differences between Kazakh (0.54) and the world population were statistically significant (p < 0.05). The frequency of GSTP1 (rs1695) in the African American population was 42%. The frequency of GSTP1 in Asian populations varied from 11% to 23%. The frequency in Caucasoid populations was around 30%. The differences between Kazakh population (0.27) and other populations selected were statistically significant (p < 0.05).The study of mutations in GSTP1 and NAT2 genes is necessary in assessing the risk of the development of various diseases, such as cancer. Information on allelic polymorphisms might also be useful for personal perscriptions such as cyclophosphamide, cisplatin, methotrexate, isoniazid, pyrazinamide, and rifampin.

Vaccination is a crucial part of the brucellosis eradication programs worldwide. A live vaccine strain of Brucella abortus 82 has been successfully used for the vaccination of cattle against brucellosis in the former Soviet republics for the last 39 years. Here, we report the genome sequence of Brucella abortus 82.

We report the 6,548-Mb genome sequence of Rhodococcus erythropolis strain DN1, isolated from the oil-contaminated soil in the Karagandy region of Kazakhstan. The draft genome sequence of strain DN1 might provide new insights into the genetic mechanisms of crude oil biodegradation.