Polymorphisms in genes involved in the absorption, distribution, metabolism, and excretion of drugs in the Kazakhs of Kazakhstan

A list of SNPs that were not found in heterozygous or homozygous variants. (DOC 83 kb

Mitochondrial and Y-chromosomal profile of the Kazakh population from East Kazakhstan

Aim To study the genetic relationship of Kazakhs from East Kazakhstan to other Eurasian populations by examining paternal and maternal DNA lineages. Methods Whole blood samples were collected in 2010 from 160 unrelated healthy Kazakhs residing in East Kazakhstan. Genomic DNA was extracted with Wizard® genomic DNA Purification Kit. Nucleotide sequence of hypervariable segment I of mitochondrial DNA (mtDNA) was determined and analyzed. Seventeen Y-short tandem repeat (STR) loci were studied in 67 samples with the Amp- FiSTR Y-filer PCR Amplification Kit. In addition, mtDNA data for 2701 individuals and Y-STR data for 677 individuals were retrieved from the literature for comparison. Results There was a high degree of genetic differentiation on the level of mitochondrial DNA. The majority of maternal lineages belonged to haplogroups common in Central Asia. In contrast, Y-STR data showed very low genetic diversity, with the relative frequency of the predominant haplotype of 0.612. Conclusion The results revealed different migration patterns in the population sample, showing there had been more migration among women. mtDNA genetic diversity in this population was equivalent to that in other Central Asian populations. Genetic evidence suggests the existence of a single paternal founder lineage in the population of East Kazakhstan, which is consistent with verbal genealogical data of the local tribes

Effect of Plant Preservative Mixture^TM on Endophytic Bacteria Eradication from In Vitro-Grown Apple Shoots

Endophytic contaminants are a common problem for the in vitro propagation of woody plants and have significant economic repercussions for the conservation of plant genetic resources and commercial micropropagation. In this study, first, the microbial contamination that appeared around the base of in vitro-grown apple shoots was identified as Bacillus megaterium. Then, plant preservative mixture (PPMTM) was used as a bactericidal agent in plant tissue culture. Its efficacy for eradicating endophytic B. megaterium in in vitro cultures of apple was tested. In vitro-contaminated shoots were grown in tissue culture medium supplemented with 0.2% v/v PPMTM for 12 weeks and then transferred to medium without any PPMTM and cultured for 24 weeks. This study showed that PPMTM is an effective agent for controlling the growth of B. megaterium. Our results highlight the species-specific response of apple shoots to PPMTM. PPMTM was effective in controlling endogenous microbial contaminations from apple varieties ‘Golden Delicious’, ‘Landsberger Renette’, ‘Suislepper’, and ‘Aport krovavo-krasnyi’; meanwhile, in ‘KG 7’ and ‘Gold Rush’, all the plants grown in the absence of PPMTM were still bacterially contaminated, even though they were pre-treated for 12 weeks in PPMTM-supplemented medium. These results therefore suggest the essentiality of further testing of extended incubation of PPMTM in these cultivars that had outbreaks of bacterial contamination

A Novel Mutation in a Kazakh Family with X-Linked Alport Syndrome.

Alport syndrome is a genetic condition that results in hematuria, progressive renal impairment, hearing loss, and occasionally lenticonus and retinopathy. Approximately 80% of Alport syndrome cases are caused by X-linked mutations in the COL4A5 gene encoding type IV collagen. The objective of this study was to define the SNP profiles for COL4A5 in patients with hereditary nephritis and hematuria. For this, we examined four subjects from one Kazakh family clinically affected with X-linked Alport syndrome due to COL4A5 gene mutations. All 51 exons of the COL4A5 gene were screened by linkage analysis and direct DNA sequencing, resulting in the identification of a novel mutation (G641E) in exon 25. The mutation was found only in two affected family individuals but was not present in healthy family members or 200 unrelated healthy controls. This result demonstrates that this novel mutation is pathogenic and has meaningful implications for the diagnosis of patients with Alport syndrome

THE MEDIEVAL MONGOLIAN ROOTS OF YCHROMOSOMAL LINEAGES FROM SOUTH KAZAKHSTAN

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. Keywords: Human genetics, Y-chromosome, Short tandem repeat, Single nucleotide polymorphism, Time to the most recent common ancestor, Kazakh, Mongol, Wusu

Development and Evaluation of Alternative Methods to Identify the Three Most Common Serotypes of <i>Salmonella enterica</i> Causing Clinical Infections in Kazakhstan

In this study, we aimed to compare the performance of conventional PCR and real-time PCR assays as screening methods for identification of three frequent, clinically significant Salmonella serovars in Kazakhstan. We determined the diagnostic efficacy of three molecular methods for detection of S. enterica subsp. enterica and typing S. Typhimurium, S. Enteritidis, and S. Virchow. A total of 137 clinical samples and 883 food samples were obtained in Almaty in 2018–2019. All tests showed high analytical specificity for detecting S. enterica and its corresponding serovariants (100%). The sensitivity of real-time PCR for each of the tested targets was 1–10 microbial cells and in conventional PCR 10–100 microbial cells. The trials with conventional PCR and real-time PCR had a diagnostic efficacy (DE) of 100% and 99.71%, respectively. The DE of real-time PCR and conventional PCR for detecting S. Enteritidis and S. Typhimurium was 99.90%, while the DE of conventional PCR and real-time PCR for detecting S. Virchow was 99.31% and 99.80%, respectively. The RAPD-PCR analysis of the genomic DNA of Salmonella enterica showed the genetic kinship of S. Enteritidis isolates, and the genetic heterogeneity of S. Typhimurium and S. Virchow isolates. Thus, the developed methods can be considered as alternatives to classical serotyping using antisera

Development and Evaluation of Alternative Methods to Identify the Three Most Common Serotypes of Salmonella enterica Causing Clinical Infections in Kazakhstan

In this study, we aimed to compare the performance of conventional PCR and real-time PCR assays as screening methods for identification of three frequent, clinically significant Salmonella serovars in Kazakhstan. We determined the diagnostic efficacy of three molecular methods for detection of S. enterica subsp. enterica and typing S. Typhimurium, S. Enteritidis, and S. Virchow. A total of 137 clinical samples and 883 food samples were obtained in Almaty in 2018–2019. All tests showed high analytical specificity for detecting S. enterica and its corresponding serovariants (100%). The sensitivity of real-time PCR for each of the tested targets was 1–10 microbial cells and in conventional PCR 10–100 microbial cells. The trials with conventional PCR and real-time PCR had a diagnostic efficacy (DE) of 100% and 99.71%, respectively. The DE of real-time PCR and conventional PCR for detecting S. Enteritidis and S. Typhimurium was 99.90%, while the DE of conventional PCR and real-time PCR for detecting S. Virchow was 99.31% and 99.80%, respectively. The RAPD-PCR analysis of the genomic DNA of Salmonella enterica showed the genetic kinship of S. Enteritidis isolates, and the genetic heterogeneity of S. Typhimurium and S. Virchow isolates. Thus, the developed methods can be considered as alternatives to classical serotyping using antisera

ANALYSIS OF BACTEROIDES FRAGILIS CLINICAL STRAINS ISOLATED IN KAZAKHSTAN

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

Genetic risk factors for restenosis after percutaneous coronary intervention in Kazakh population

Background: After coronary stenting, the risk of developing restenosis is from 20 to 35 %. The aim of the present study is to investigate the association of genetic variation in candidate genes in patients diagnosed with restenosis in the Kazakh population. Methods: Four hundred fifty-nine patients were recruited to the study; 91 patients were also diagnosed with diabetes and were excluded from the sampling. DNA was extracted with the salting-out method. The patients were genotyped for 53 single-nucleotide polymorphisms. Genotyping was performed on the QuantStudio 12K Flex (Life Technologies). Differences in distribution of BMI score among different genotype groups were compared by analysis of variance (ANOVA). Also, statistical analysis was performed using R and PLINK v.1.07. Haplotype frequencies and LD measures were estimated by using the software Haploview 4.2. Results: A logistic regression analysis found a significant difference in restenosis rates for different genotypes. FGB (rs1800790) is significantly associated with restenosis after stenting (OR = 2.924, P = 2.3E−06, additive model) in the Kazakh population. CD14 (rs2569190) showed a significant association in the additive (OR = 0.08033, P = 2.11E−09) and dominant models (OR = 0.05359, P = 4.15E−11). NOS3 (rs1799983) was also highly associated with development of restenosis after stenting in additive (OR = 20.05, P = 2.74 E−12) and recessive models (OR = 22.24, P = 6.811E−10). Conclusions: Our results indicate that FGB (rs1800790), CD14 (rs2569190), and NOS3 (rs1799983) SNPs could be genetic markers for development of restenosis in Kazakh population. Adjustment for potential confounder factor BMI gave almost the same results