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.     

Microsatellite haplotypes of the Y-chromosome demonstrate the absence of subdivisions and presence of several components in the Tuvinian male gene pool

The haplotype analysis of seven Y-chromosome microsatellites in three regional populations of Tuvinians revealed high intrapopulation variation in the male gene pool of the modern population of the Tuva Republic. In total, 49 haplotypes were found in 111 individuals; only four haplotypes occurred at a frequency higher than 5%. High genetic diversity (H = 0.935) suggested a high power of discrimination for the Y-chromosome haplotypes. The analysis of molecular variance (AMOVA) and other data did not reveal subdivision of the Tuvinian population with respect to Y-chromosome haplotypes. Most haplotypes found in Tuvinians formed two lines. Line A included approximately 64% of the haplotypes found, line B, approximately 24%. A putative ancestral haplotype of line B was similar to a haplotype most common in modern Caucasoids (Md = 3), whereas a putative ancestral haplotype of line A proved to be distant from the ancestral haplotype of line A and haplotypes common for Caucasoids and Mongoloids. Estimates of the age of the Y-chromosome lines showed that the male gene pool of modern Tuvinians originated in the late Paleolithic or Neolithic period. With two methods, the age of line A was estimated at 3500 or 18,000 years and the age of line B was approximately at 5500 or 15,000 years. Considering the less conservative estimates to be more reliable, line B was assumed to originate from the ancient Caucasoid population of the Tuva region. The more widespread and evolutionarily younger line A was associated with the peopling region by ancient Mongoloid tribes of the Turkic language group in the Hun-Sarmatian period.     

Haplotypes of two diallelic Y chromosome loci in the indigenous and migrant populations of Siberia

Two diallelic Y-chromosome markers, the Y Alu polymorphism (YAP) and the T-C transition (Tat), were analyzed in the indigenous (Tuvinian, Buryat, Northern Altaic, and Tatar) and migrant (Slavic) populations of Siberia. A high frequency of the allele C was revealed in several indigenous populations (25-55%) and in Russians (20.8%). The YAP+ allele occurred at a surprisingly high frequency (31.4%) and was completely linked with the C allele in Buryats. The YAP+ chromosome was also found in the Tuvinian population (1.5%). The two diallelic loci showed a marked linkage disequilibrium (D = 92.4%) in the total sample. The YAP-/T and YAP-/C haplotypes prevailed in both indigenous and migrant populations: their respective frequencies were 80.4 and 19.6% in the Slavic population and 71.8 and 19.9%, respectively, in the indigenous one. The YAP+/C (7.8%) and YAP+/T (0.5%) haplotypes were found only in the indigenous population. An appreciable heterogeneity in haplotype frequency distribution between regional subpopulations was revealed in Russians, Tuvinians, and Buryats. The origin and evolution of Y-chromosome lines in Northern Asia are considered.     

Analysis of distribution of "mongoloid" haplogroups of mitochondrial DNA among indigenous population of the Tuva Republic

Variation of Mongoloid-specific restriction sites of mitochondrial genome was analyzed in three territorial groups of Tuvinians. Distribution of mitochondrial DNA haplogroups A, B, C, and D on the territory of the Tuva Republic was estimated. The populations studied did not display distinct differentiation in respect to the mtDNA polymorphism. The specific feature of Tuvinian mitochondrial gene pool was the prevalence of only one haplogroup C (over 40%), mainly represented by two mitotypes. The high frequency of this haplogroup makes Tuvinians similar to more northern Siberian populations. On the other hand, the presence of haplogroup B indicates that Tuvinians have affinity to ethnic groups of Central Asia.     

Genome-wide association study of allergic diseases in Russians of West Siberia

Genome-wide association studies are currently considered as one of the most powerful tools for establishing the genetic basis of complex diseases. A number of such studies have been carried out for allergic diseases; however, in the Russian population, this analysis has not been performed so far. For the first time, we performed a genome-wide association study of allergic diseases in Russian residents of West Siberia. Two new loci associated with childhood bronchial asthma (20q13.12, rs2425656, P = 1.99 × 10⁻⁷; 1q32.1, rs3817222, rs12734001, P = 2.18 × 10⁻⁷ and 2.79 × 10⁻⁷, respectively) as well as one locus associated with allergic rhinitis (2q36.1, rs1597167, P = 3.69 × 10⁻⁷) were identified. Genes located in these loci, YWHAB and PPP1R12B for asthma and KCNE4 for allergic rhinitis, are suggested as new candidate genes for these diseases. It was also found that BAT1 (6p21.33), MAGI2 (7q21.11), and ACPL2 (3q23) are probably common (syntropic) genes of allergic disease and atopic sensitization. It was shown that RIT2 (18q12.3) and FSTL4 (5q31.1) genes can be involved in the control of lung function. The results of the study contribute to the body of data on genetic factors of allergy and expand the list of genes underlying these diseases.     

Evaluation of diagnostic efficiency of the recombinant protein modeling immunodominant epitope V3 of envelope gp120 for immunoenzyme detection for HIV-1 infection antibodies

The third hypervariable domain V3 of the human immunodeficiency virus type 1 gpl20 envelope glycoprotein contains neutralizing epitopes and plays an important role in the diagnosis of HIV infection . Neutralizing antibodies bind to conserved epitope with sequence GPG of V3 loop. The effect of sequence variation on the antigenic properties of the V3 epitope gp120 was studied using five synthetic peptides. The amino acid sequence of the peptide corresponding to the V3 region gp120 of HIV-1 subtype C showed the highest immunoreactivity. The DNA fragment encoding V3-C region gp120 was synthesized by polymerase chain reaction and cloned into pET41b vector. The recombinant plasmid was expressed in the E. coli cells, and recombinant protein was purified using glutathione-S sepharose affinity chromatography. The serological activity of the recombinant protein was tested using ELISA and compared to activity of similar synthetic peptide. The results of this study showed that most immunoreactive agent was the amino acid sequence of V3 region gp120 of HIV-1 subtype C. The recombinant antigen comprising this sequence was more antigenic than synthetic peptide with the same sequence. The evaluation of this antigen shows that this protein is a good candidate for the immunoassay development.     

Insights into pathophysiology of dystropy through the analysis of gene networks: an example of bronchial asthma and tuberculosis

Co-existence of bronchial asthma (BA) and tuberculosis (TB) is extremely uncommon (dystropic). We assume that this is caused by the interplay between genes involved into specific pathophysiological pathways that arrest simultaneous manifestation of BA and TB. Identification of common and specific genes may be important to determine the molecular genetic mechanisms leading to rare co-occurrence of these diseases and may contribute to the identification of susceptibility genes for each of these dystropic diseases. To address the issue, we propose a new methodological strategy that is based on reconstruction of associative networks that represent molecular relationships between proteins/genes associated with BA and TB, thus facilitating a better understanding of the biological context of antagonistic relationships between the diseases. The results of our study revealed a number of proteins/genes important for the development of both BA and TB.     

Hereditary diseases among Yakuts

Several forms of pathologies, referred to as Yakut hereditary diseases, have been distinguished on the basis of the results of genetic epidemiological studies of Mendelian diseases in the population of the Republic of Sakha (Yakutia): spinocerebellar ataxia type I, myotonic dystrophy, oculopharyngeal muscular dystrophy, hereditary enzymopenic methemoglobinemia, and 3-M syndrome. These diseases are characterized by a high prevalence among Yakuts as compared to their global incidence in the. Data on the molecular nature of mutations in genes responsible for these hereditary diseases are presented.     

Comparative Phylogenetic Study of Native North Eurasian Populations Using a Panel of Autosomal Microsatellite Loci

Genetic relationships among eight Siberian and Central Asian ethnic groups were examined using autosomal microsatellite loci. Genetic similarity of Buryats and Evenks, as well as close relationships between Tuvinians and Kyrgyzes, most likely resulting from the Altai-Slavic co-ancestry of their gene pools, was demonstrated. Studies of gene flow in these populations demonstrated that, in general, Turkic ethnic groups of Southern Siberia (Altaians and Tuvinians) were the recipients of more intense gene flow compared to Eastern Siberian populations belonging to Altaic family. The local Buryat populations displayed substantial differences in the direction and the level of deviation of the observed gene diversity from the expected one, which was probably caused by the differences in the degree of isolation and/or in effective population sizes.