Haplotype of Y-chromosomes in the Central Asia population

The distribution of alleles and haplotypes of three diallellic Y-specific loci (YAP, DYF155S2, and Tat) in the populations of Kyrgyz, Uzbeks and Tajiks was analyzed. In Kyrgyzes and Uzbeks, a relatively high frequency of the DYF155S2 deletion (20 and 12.5%, respectively) and the C allele at the Tat locus (11.2 and 8.3%, respectively) were revealed. In the populations of southern Kyrgyzes and Uzbeks, two chromosomes carrying the YAP+ allele were detected. In both cases the YAP+ allele was found within the YAP+/DYF155S2+/TatT haplotype. The Tajik population was monomorphic in respect to the polymorphisms studied. The Tajiks demonstrated the presence of only the YAP-/DYF155S2+/TatT haplotype. This haplotype appeared to be most frequent in Kyrgyz (78.8%) and Uzbeks (83.3%). The question on the origin and the distribution of Y-chromosome variants in Eurasia are discussed.     

An essential saccharide binding domain for the mAb 2C7 established for Neisseria gonorrhoeae LOS by ES-MS and MSn

A study of bacterial surface oligosaccharides were investigated among different strains of Neisseria gonorrhoeae to correlate structural features essential for binding to the MAb 2C7. This epitope is widely expressed and conserved in gonococcal isolates, characteristics essential to an effective candidate vaccine antigen. Sample lipooligosaccharides (LOS), was prepared by a modification of the hot phenol-water method from which de-O-acetylated LOS and oligosaccharide (OS) components were analyzed by ES-MS-CID-MS and ES-MSnin a triple quadrupole and an ion trap mass spectrometer, respectively. Previously documented natural heterogeneity was apparent from both LOS and OS preparations which was admixed with fragments induced by hydrazine and mild acid treatment. Natural heterogeneity was limited to phosphorylation and antenni extensions to the alpha-chain. Mild acid hydrolysis to release OS also hydrolyzed the beta(1-->6) glycosidic linkage of lipid A. OS structures were determined by collisional and resonance excitation combined with MS and multistep MSn which provided sequence information from both neutral loss, and nonreducing terminal fragments. A comparison of OS structures, with earlier knowledge of MAb binding, enzyme treatment, and partial acid hydrolysis indicates a generic overlapping domain for 2C7 binding. Reoccurring structural features include a Hepalpha(1-->3)Hepbeta(1-->5)KDO trisaccharide core branched on the nonreducing terminus (Hep-2) with an alpha(1-->2) linked GlcNAc (gamma-chain), and an alpha-linked lactose (beta-chain) residue. From the central heptose (Hep-1), a beta(1-->4) linked lactose (alpha-chain), moiety is required although extensions to this residue appear unnecessary.      

Frequencies of Y chromosome binary haplogroups in Belarussians

The compositions and frequencies of Y-chromosome haplogroups identified by genotyping 23 biallelic loci of its nonrecombining region (YAP, 92R7, DYF155S2, 12f2, Tat, M9, M17, M25, M89, M124, M130, M170, M172, M174, M173, M178, M201, M207, M242, M269, P21, P25, and P37) have been determined in a sample of 68 Belarussians. Eleven haplogroups have been found in the Belarussian gene pool (E, F*, G, I, I1b, J2, N3a*, Q*, R1*, R1a1, and R1b3). Haplogroup R1a1 is the most frequent; it includes 46% of all Y chromosomes in this sample. The frequencies of haplogroups I1b and I are 17.6 and 7.3%, respectively. Haplogroup N3a* is the next in frequency. The frequencies of haplogroups E, J2, and R1b3 are 4.4% each; that of R1* is 3%; and those of F*, G, and Q* are 1.5% each.     

Genetic diversity of Khakassian gene pool: subethnic differensiation and the structure of Y-chromosome haplogroups,

The structure of Khakass gene pool has been investigated: compositions and frequencies of Y-chromosome haplogroups were described in seven population samples of two basic subethnic groups--Sagays and Kachins from three territorially distanced regions of Khakassia Republic. Eight haplogroups: C3, E, N*, N1b, N1c, R1a1a and R1b1b1 have been determined in Khakass gene pool. Significant differences between Sagays and Kachins were shown in haplogroup spectra and a level of genetic diversity in haplogroups and YSTR-haplotypes. Kachin samples are characterized by a low value of gene diversity, whereas the level of Sagay diversity is similar to that of other South-Siberian ethnoses. Sagay samples from Askizsky region are very similar to each other just as two Kachin samples from Shirinsky region, while Sagay samples from Tashtypsky region greatly differ from each other. A great portion of intergroup differences was determined among different ethnic groups, which testifies to significant genetic differentiation of native populations in Khakassia. Khakass gene pool is greatly differentiated both in haplogroup frequencies and in YSTR-haplotypes within N1b haplogroup. Frequencies and molecular phylogenesis of YSTR-haplotypes were revealed within N1b, N1c and R1a1 haplogroups of Y-chromosome. We carried out comparative analysis of the data obtained. The results of factor, cluster and dispersion analyses are evidence of structuredness of Khakass gene pool according to territorial-subethnic principle.     

Association analysis of gene polymorphism in alcohol metabolizing enzymes with risk for coronary atherosclerosis

The allele and genotype distribution of two alcohol dehydrogenase genes ADH1B (exon 3 polymorphism A/G (47His)), ADH7 (intron 5 polymorphism G/C) and cytochrome P450 2E1 gene (CYP2E1; 5'-flanking region G/C and intron 6 T/A polymorphisms) were examined in Russian (Tomsk, n = 125) healthy population and in coronary atherosclerosis patients (CA, n = 92). The genotype frequencies followed the Hardy-Weinberg equilibrium and the alleles were in linkage equilibrium or gametic equilibrium in the control sample. Only two CYP2E1 gene polymorphisms were in linkage disequilibrium. The frequencies of the derived alleles at ADH1B (*G (+MslI) allele), CYP2E1 (**C2 (+PstI) allele) and CYP2E1 (*C (-Dra I)2 allele) were 8.48 +/- 1.86%; 1.20 +/- 0.69% and 10.00 +/- 1.90%, respectively. The 2ADH7 gene polymorphism showed a high level of heterozygosity; the frequency of the ADH7*C (-Sty I) allele was 44.58 +/- 3.21%. A significantly higher frequency of CYP2E1 (*C2 (+Pst I)) allele has been revealed in the CA group (P = 0.043; OR = 4.23; 95% CI 1.03-20.01). The tendency to significant effect of A1A2 genotype in ADH1B Msl 1 polymorphism was observed for systolic blood pressure in the control group (P = 0.068). The statistically significant two-way interaction effects of ADH7 StyI and CYP2E1 DraI on diastolic blood pressure (P = 0.029) and on the serum high density lipoprotein level (P = 0,042) were also revealed. Association of A1A2 genotype in ADHIB Msl I polymorphism with reduced amount in a serum of a very low density lipoprotein level (P = 0.045) have also been shown. This may result from multifunctional activity of alcohol metabolizing enzymes and their involvement in many metabolic and free radical reactions in the body.     

Gene pool differences between northern and southern Altaians inferred from the data on Y-chromosomal haplogroups

Y-chromosomal haplogroups composition and frequencies were analyzed in Northern and Southern Altaians. In the gene pool of Altaians a total of 18 Y-chromosomal haplogroups were identified, including C3xM77, C3c, DxM15, E, F*, J2, I1a, I1b, K*, N*, N2, N3a, O3, P*, Q*, R1*, R1a1, and R1b3. The structured nature of the Altaic gene pool is determined by the presence of the Caucasoid and Mongoloid components, along with the ancient genetic substratum, marked by the corresponding Western and Eastern Eurasian haplogroups. Haplogroup R1a1 prevailed in both ethnic groups, accounting for about 53 and 38% of paternal lineages in Southern and Northern Altaians, respectively. This haplogroup is thought to be associated with the eastward expansion of early Indo-Europeans, and marks Caucasoid element in the gene pools of South Siberian populations. Similarly to haplogroup K*, the second frequent haplogroup Q* represents paleo-Asiatic marker, probably associated with the Ket and Samoyedic contributions to the Altaic gene pool. The presence of lineages N2 and N3a can be explained as the contribution of Finno--Ugric tribes, assimilated by ancient Turks. The presence of haplogroups C3xM77, C3c, N*, and 03 reflects the contribution of Central Asian Mongoloid groups. These haplogroups, probably, mark the latest movements of Mongolian migrants from the territory of contemporary Tuva and Mongolia. The data of factor analysis, variance analysis, cluster analysis, and phylogenetic analysis point to substantial genetic differentiation of Northern and Southern Altaians. The differences between Northern and Southern Altaians in the haplogroup composition, as well as in the internal haplotype structure were demonstrated.     

Genetic diversity of X-chromosome in populations of aboriginal Siberian ethnic groups: linkage disequilibrium structure and haplotype philogeography of ZFX locus

The structure of gene pool of the Siberian aboriginal population has been described based on the data on polymorphism of ZFX gene located on X-chromosome. In ten populations under study 49 haplotypes have been determined, three of which are presented with high frequency. Comparing the obtained results with the available data from HapMap project unique "African" haplotypes were revealed, which occurred in Yoruba population with the frequency of 3-7% and were not found in other populations. A coefficient of genetic differentiation of the Siberian ethnic groups under study amounted to 0.0486. Correlation analysis involving Mantel test did not reveal any significant correlations between a matrix of genetic distances and the matrices of geographic, linguistic and anthropological differences, where a maximum coefficient was obtained at the comparison with the anthropological matrix. Phylogenetic analysis proved strong isolation of African population from the other investigated ethnic groups. The Siberian populations were subdivided into two separate clusters: the first one included Yakuts, Buryats and Kets, while the second cluster included Altaians, Tuvinians and Khanty. A principal component analysis enabled to combine the investigated populations in three groups, which clearly differed by a degree of manifestation of Caucasoid and Mongoloid components. The first group included Europe inhabitants and one of Khanty populations, the second one--populations of South Siberia and China inhabitants. Mongoloid populations of East Siberia, the Japanese and Kets were combined in the third group. The results of barrier analysis revealed similar structure of genetic differentiation in the Siberian population. Linkage disequilibrium structure was obtained for six ethnic groups of Siberia. A unified linkage block by ten SNP of ZFX gene was found in five of the presented ethnic groups (excluding Ket population).