Ethnogenesis of Kazakhs took place in Central Asia, a region of high genetic and cultural diversity. Even though archaeological and historical studies have shed some light on the formation of modern Kazakhs, the process of establishment of hierarchical socioeconomic structure in the Steppe remains contentious. In this study, we analyzed haplotype variation at 15 Y-chromosomal short-tandem-repeats obtained from 1171 individuals from 24 tribes representing the three socio-territorial subdivisions (Senior, Middle and Junior zhuz) in Kazakhstan to comprehensively characterize the patrilineal genetic architecture of the Kazakh Steppe. In total, 577 distinct haplotypes were identified belonging to one of 20 haplogroups; 16 predominant haplogroups were confirmed by SNP-genotyping. The haplogroup distribution was skewed towards C2-M217, present in all tribes at a global frequency of 51.9%. Despite signatures of spatial differences in haplotype frequencies, a Mantel test failed to detect a statistically significant correlation between genetic and geographic distance between individuals. An analysis of molecular variance found that ∼8.9% of the genetic variance among individuals was attributable to differences among zhuzes and ∼20% to differences among tribes within zhuzes. The STRUCTURE analysis of the 1164 individuals indicated the presence of 20 ancestral groups and a complex three-subclade organization of the C2-M217 haplogroup in Kazakhs, a result supported by the multidimensional scaling analysis. Additionally, while the majority of the haplotypes and tribes overlapped, a distinct cluster of the O2 haplogroup, mostly of the Naiman tribe, was observed. Thus, firstly, our analysis indicated that the majority of Kazakh tribes share deep heterogeneous patrilineal ancestries, while a smaller fraction of them are descendants of a founder paternal ancestor. Secondly, we observed a high frequency of the C2-M217 haplogroups along the southern border of Kazakhstan, broadly corresponding to both the path of the Mongolian invasion and the ancient Silk Road. Interestingly, we detected three subclades of the C2-M217 haplogroup that broadly exhibits zhuz-specific clustering. Further study of Kazakh haplotypes variation within a Central Asian context is required to untwist this complex process of ethnogenesis.

Background Glutamate cysteine ligase (GCL) is a rate-limiting enzyme in synthesis of glutathione. Evidence suggests that genetic variations in the promoter region of genes coding a catalytic subunit (GCLC -129T/C) and a modifier subunit (GCLM -588C/T) of GCL have a functional impact on their transcriptional activity and were associated with various disorders. Hence, we hypothesize whether these two polymorphic variants of GCLM and GCLC genes are associated with the risk of ischemic heart disease (IHD) development in the population of Kazakhstan. Methods We evaluated 360 patients with IHD and 341 control subjects. Allele frequencies of studied promoters' polymorphisms were detected by PCR-RFLP analysis. Multiple logistic regression analysis was applied to assess the risk for different genotypes obtained. Results The presence of -588T allele in GCLM and -129T allele in GCLC gene genotypes was associated with an increased risk of IHD (GCLM -588T: OR = 3.92, p = 0.003; GCLC -129T: OR = 3.22, p = 0.03) for general ethnically mixed group. Analysis of each ethnical groups separately showed the higher risk tendency for Kazakhs as for GCLM -588T (OR = 4.79; p = 0.03) and as for GCLC -129T (OR = 4.79, p = 0.03). For Russians, statistically differences for two polymorphisms were not observed. Conclusion The two promoter polymorphisms of GCLM (-588C/T) and GCLC (-128T/C) are associated with an increased risk of IHD in Kazakhstan population.

Autism spectrum disorders (ASDs) are heterogeneous diseases that are triggered by a number of environmental and genetic factors. The aim of the current study was to investigate an association of the rs1799836 genetic variant of the neurotransmitter-related gene MAOB with ASDs. In total, 262 patients diagnosed with ASDs and their 126 healthy siblings were included in the present study. All individuals represented a Kazakhstani population. The distributions of the rs1799836 genotype were in accordance with the Hardy-Weinberg equilibrium among both cases and controls. No statistically significant differences were found in the allelic distributions of this polymorphism between ASD and control subjects (A/G: for males OR=1.11, 95% 0.59-2.06, p=0.75; for females OR=1.14, 95% 0.70-1.86, p=0.76). However, the increased score in the overall CARS was significantly associated with the A allele of rs1799836 MAOB for females (OR=2.31, 95% 1.06-5.04, p=0.03). The obtained results suggest that the rs1799836 polymorphism of the MAOB gene may have little contribution to the development of ASDs but may be involved in pathways contributing to ASD symptom severity in females. Further large-scale investigations are required to uncover possible relationships between rs1799836 MAOB and ASD progression in a gender-specific manner and their possible application as a therapeutic target.

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