Kazak mitochondrial genomes provide insights into the human population history of Central Eurasia.

As a historical nomadic group in Central Asia, Kazaks have mainly inhabited the steppe zone from the Altay Mountains in the East to the Caspian Sea in the West. Fine scale characterization of the genetic profile and population structure of Kazaks would be invaluable for understanding their population history and modeling prehistoric human expansions across the Eurasian steppes. With this mind, we characterized the maternal lineages of 200 Kazaks from Jetisuu at mitochondrial genome level. Our results reveal that Jetisuu Kazaks have unique mtDNA haplotypes including those belonging to the basal branches of both West Eurasian (R0, H, HV) and East Eurasian (A, B, C, D) lineages. The great diversity observed in their maternal lineages may reflect pivotal geographic location of Kazaks in Eurasia and implies a complex history for this population. Comparative analyses of mitochondrial genomes of human populations in Central Eurasia reveal a common maternal genetic ancestry for Turko-Mongolian speakers and their expansion being responsible for the presence of East Eurasian maternal lineages in Central Eurasia. Our analyses further indicate maternal genetic affinity between the Sherpas from the Tibetan Plateau with the Turko-Mongolian speakers.

Draft Genome Sequences of Two Clinical Isolates of Mycobacterium tuberculosis from Sputum of Kazakh Patients.

Here, we report the draft genome sequences of two clinical isolates of Mycobacterium tuberculosis (MTB-476 and MTB-489) isolated from sputum of Kazakh patients.

Genetic Diversity of IFγ, IL1ß, TLR2, and TLR8 Loci in Pulmonary Tuberculosis in Kazakhstan.

INTRODUCTION: Tuberculosis (TB) is caused by bacterium Mycobacterium tuberculosis (MTB), and according to the WHO, up to 30% of world population is infected with latent TB. Pathogenesis of TB is multifactorial, and its development depends on environmental, social, microbial, and genetic factors of both the bacterium and the host. The number of TB cases in Kazakhstan has decreased in the past decade, but multidrug-resistant (MDR) TB cases are dramatically increasing. Polymorphisms in genes responsible for immune response have been associated with TB susceptibility. The objective of this study was to investigate the risk of developing pulmonary TB (PTB) associated with polymorphisms in several inflammatory pathway genes among Kazakhstani population. METHODS: 703 participants from 3 regions of Kazakhstan were recruited for a case-control study. 251 participants had pulmonary TB (PTB), and 452 were healthy controls (HC). Males and females represented 42.39% and 57.61%, respectively. Of all participants, 67.4% were Kazakhs, 22.8% Russians, 3.4% Ukrainians, and 6.4% were of other origins. Clinical and epidemiological data were collected from medical records, interviews, and questionnaires. DNA samples were genotyped using TaqMan assay on 4 polymorphisms: IFNγ (rs2430561) and IL1ß (rs16944), TLR2 (rs5743708) and TLR8 (rs3764880). Statistical data was analyzed using SPSS 19. RESULTS: Genotyping by IFγ, IL1ß, TLR2 showed no significant association with PTB susceptibility (p > 0.05). TLR8 genotype A/G was significantly higher in females (F/M - 41.5%/1.3%) and G/G in males (M/F - 49%/20.7%) (χ2=161.43, p < 0.001). A significantly increased risk of PTB development was observed for TLR A/G with an adjusted OR of 1.48 (95%, CI: 0.96 - 2.28), and a protective feature was revealed for TLR8 G/G genotype (OR: 0.81, 95%, CI: 0.56 - 1.16, p = 0.024). Additional grouping by gender revealed that TLR8 G/G contributes as protective genotype (OR: 1.83, 95%, CI: 1.18 - 2.83, p = 0.036) in males of the control group. CONCLUSION: Results indicate that heterozygous genotype A/G of TLR8 increases the risk of PTB development, while G/G genotype may serve as protection mechanism. A/A genotype is strongly associated with susceptibility to PTB. To clarify the role of other polymorphisms in susceptibility to PTB in Kazakhstani population, further investigations are needed.

Vitamin D Receptor Gene Polymorphisms in Susceptibility to Tuberculosis in the Kazakh Population in Almaty and Almaty Area.

INTRODUCTION: Vitamin D receptor (VDR) plays an important role in activating the immune response against various infectious agents. It is known that the active metabolite of ligand receptor Vitamin D (1,25 - dihydroxyvitamin D) is encoded by VDR and helps mononuclear phagocytes to suppress the intracellular growth of M. tuberculosis. The VDR gene harbors approximately 200 polymorphisms, some of which are linked to differences in receptor Vitamin D uptake and therefore can be considered as candidate disease risk variants. The relation between VDR gene polymorphisms and susceptibility to TB has been studied in different populations. There is not a great deal of information regarding the association of these SNPs with TB risk in the Kazakh population. The four most commonly investigated VDR polymorphisms in association with different diseases, including susceptibility to tuberculosis, are located in exon 2 (rs2228570 or FokI), intron 8 (rs1544410 or BsmI and rs7975232 or ApaI), and exon 9 (rs731236 or TaqI). The aim of our study was to determine whether these four VDR gene single nucleotide polymorphisms were associated with TB and whether they were a risk for the development of TB in the Kazakh Population in Almaty city and Almaty area. METHODS: This study was a hospital-based case-control analysis of 283 individuals (99 TB patients and 184 healthy controls). Genotyping was performed by Taqman SNP allelic discrimination using commercial TaqMan SNP Genotyping assays. Statistical analysis was conducted using SPSS Version 19.0 software. RESULTS: Genotype frequencies for the Kazakh population are close to world (HapMap) data on Asian populations. FokI and ApaI polymorphisms genotypes tend to be associated with TB risk under the co-dominant model [OR=1.18; 95%CI: (0.68, 2.07), p=0.15] for FokI and [OR=1.33; 95%CI: (0.61, 2.91), p=0.6] for ApaI. No significant association between the disease and TaqI, BsmI genotypes was observed. CONCLUSIONS: In summary, we explored potential associations between SNPs in the VDR (FokI, ApaI) gene and susceptibility to tuberculosis in the Kazakh Population, which requires further detailed analysis with a larger sample size and greater geographic diversity including other regions of Kazakhstan.

Whole genome sequencing of M.tuberculosis in Kazakhstan: preliminary data.

BACKGROUND: Tuberculosis is a major public health problem which infects one third of the world's population, resulting in more than two million deaths every year. The emergence of whole genome sequencing (WGS) technologies as a primary research tool has allowed for the detection of genetic diversity in Mycobacterium tuberculosis (MTB) with unprecedented resolution. WGS has been used to address a broad range of topics, including the dynamics of evolution, transmission, and treatment. To our knowledge, studies involving WGS of Kazakhstani strains of M. tuberculosis have not yet been performed. AIM: To perform whole genome sequencing of M. tuberculosis strains isolated in Kazakhstan and analyze sequence data (first experience and preliminary data). RESULTS: In the present report, we announce the whole-genome sequences of the two clinical isolates of Mycobacterium tuberculosis, MTB-489 and MTB-476, isolated from the Almaty region. These strains were part of a repository that was created during our project "Creating prerequisites of personalized approach in the diagnosis and treatment of tuberculosis, based on whole genome-sequencing of M. tuberculosis". Two strains were isolated from sputum samples of patients P1 and P2. Phenotypically, two isolates were drug-susceptible M. tuberculosis. Sequence data was compared with the publicly available data on M. tuberculosis laboratory strain H37Rv and others. The sequencing of the strains was performed on a Roche 454 GS FLX+ next-generation sequencing platform using a standard protocol for a shotgun genome library. The whole genome sequencing was performed for two M.tuberculosis isolates MTB-476 and MTB-489. 96 M bp with an average read length of 520 bp, approximately 21.8X coverage and 104.2 M bp with an average read length of 589 bp and approximately 23.7X coverage were generated for the MTB-476 and MTB-489, respectively. The genome of MTB-476 consists of 257 contigs, 4204 CDS, 46 tRNAs and 3 rRNAs. MTB-489 has 187 contigs, 4183 CDS, 45 tRNAs and 3rRNAs. CONCLUSION: The results of genome assembling have been submitted into NCBI GenBank and are available for public access under the accession numbers AZBA00000000 and AZAZ00000000. These genome assemblies can be useful for comparative genome analysis and for identification of novel SNPs and gene variants in genomes of M.tuberculosis.

Mitochondrial DNA and Y chromosome variation provides evidence for a recent common ancestry between Native Americans and Indigenous Altaians.

The Altai region of southern Siberia has played a critical role in the peopling of northern Asia as an entry point into Siberia and a possible homeland for ancestral Native Americans. It has an old and rich history because humans have inhabited this area since the Paleolithic. Today, the Altai region is home to numerous Turkic-speaking ethnic groups, which have been divided into northern and southern clusters based on linguistic, cultural, and anthropological traits. To untangle Altaian genetic histories, we analyzed mtDNA and Y chromosome variation in northern and southern Altaian populations. All mtDNAs were assayed by PCR-RFLP analysis and control region sequencing, and the nonrecombining portion of the Y chromosome was scored for more than 100 biallelic markers and 17 Y-STRs. Based on these data, we noted differences in the origin and population history of Altaian ethnic groups, with northern Altaians appearing more like Yeniseian, Ugric, and Samoyedic speakers to the north, and southern Altaians having greater affinities to other Turkic speaking populations of southern Siberia and Central Asia. Moreover, high-resolution analysis of Y chromosome haplogroup Q has allowed us to reshape the phylogeny of this branch, making connections between populations of the New World and Old World more apparent and demonstrating that southern Altaians and Native Americans share a recent common ancestor. These results greatly enhance our understanding of the peopling of Siberia and the Americas.