RESUMO
BACKGROUND: The haplotypes from Northern, Southern, Eastern, and Western Kazakhstan, analysed for 27 Y-STR loci, have been contributed to the Y-Chromosome STR Haplotype Reference Database, while the genetic profile of Central Kazakhstan remains inadequately explored. AIM: To investigate the genetic diversity of 27 Y-STR loci in the Kazakh populations from Central Kazakhstan. SUBJECTS AND METHODS: A total of 112 unrelated Central Kazakh males were genotyped via the Yfiler Plus kit. Data analysis yielded haplotype and allele frequencies, and forensic parameters. Genetic distances were graphically represented by a multidimensional scaling plot, with genetic linkages further elucidated through Nei's distance dendrograms and Median-joining networks. RESULTS: A total of 102 haplotypes were detected, of which 96 were unique. The haplotype diversity and discrimination capacity were 0.997 and 0.91, respectively. Central Kazakhstan displays a unique cluster in analyses, underscoring its distinct Y-chromosome diversity compared to other Kazakh regions. The analysis of the Naiman tribe, predominantly residing in Central, Southern and Eastern Kazakhstan, revealed three genetic clusters of distinct haplogroups associated with their clans. CONCLUSIONS: The identified haplotypes will enhance the existing reference database for Y-chromosomal studies in Kazakhstan, offering a robust tool for future research in population genetics, forensic science and genetic genealogy.
Assuntos
Cromossomos Humanos Y , Haplótipos , Repetições de Microssatélites , Polimorfismo Genético , Humanos , Cazaquistão , Cromossomos Humanos Y/genética , Masculino , Frequência do GeneRESUMO
BACKGROUND: The Kazakhs are one of the biggest Turkic-speaking ethnic groups, controlling vast swaths of land from the Altai to the Caspian Sea. In terms of area, Kazakhstan is ranked ninth in the world. Northern, Eastern, and Western Kazakhstan have already been studied in relation to genetic polymorphism 27 Y-STR. However, current information on the genetic polymorphism of the Y-chromosome of Southern Kazakhstan is limited only by 17 Y-STR and no geographical study of other regions has been studied at this variation. RESULTS: The Kazakhstan Y-chromosome Haplotype Reference Database was expanded with 468 Kazakh males from the Zhambyl and Turkestan regions of South Kazakhstan by having their 27 Y-STR loci and 23 Y-SNP markers analyzed. Discrimination capacity (DC = 91.23%), haplotype match probability (HPM = 0.0029) and haplotype diversity (HD = 0.9992) are defined. Most of this Y-chromosome variability is attributed to haplogroups C2a1a1b1-F1756 (2.1%), C2a1a2-M48 (7.3%), C2a1a3-F1918 (33.3%) and C2b1a1a1a-M407 (6%). Median-joining network analysis was applied to understand the relationship between the haplotypes of the three regions. In three genetic layer can be described the position of the populations of the Southern region of Kazakhstan-the geographic Kazakh populations of Kazakhstan, the Kazakh tribal groups, and the people of bordering Asia. CONCLUSION: The Kazakhstan Y-chromosome Haplotype Reference Database was formed for 27 Y-STR loci with a total sample of 1796 samples of Kazakhs from 16 regions of Kazakhstan. The variability of the Y-chromosome of the Kazakhs in a geographical context can be divided into four main clusters-south, north, east, west. At the same time, in the genetic space of tribal groups, the population of southern Kazakhs clusters with tribes from the same region, and genetic proximity is determined with the populations of the Hazaras of Afghanistan and the Mongols of China.
Assuntos
Variação Genética , Genética Populacional , Masculino , Humanos , Cazaquistão , Cromossomos Humanos Y/genética , Repetições de Microssatélites , Polimorfismo Genético , HaplótiposRESUMO
BACKGROUND: The establishment of a national haplotype database is important for forensic and genetic applications and requires studying genetic polymorphisms at Y-STR sites. However, the genetic structure of the Eastern Kazakhstan population is poorly characterised. AIM: To investigate the genetic polymorphisms of 27 Y-STR loci in the Kazakh population from Eastern Kazakhstan and analyse the population genetic relationships of the Eastern Kazakhs with other populations. SUBJECTS AND METHODS: The Yfiler Plus kit was utilised to genotype 246 healthy, unrelated males from Eastern Kazakhstan. Based on the raw data, haplotype and allele frequencies along with forensic parameters were calculated, and an MDS plot was constructed. RESULTS: A total of 207 haplotypes were detected, of which 186 were unique. The haplotype diversity and discrimination capacity were 0.997 and 0.841, respectively. Population comparisons showed that Eastern Kazakhs have close genetic relationships with Kazakhs from Xinjiang, China. At the same time, a difference was found between the studied population and the previous one in the same part of Kazakhstan. CONCLUSIONS: The obtained haplotypes will help to expand the Kazakhstan Y-chromosome reference database and will be useful for future genetic research and forensic applications.
Assuntos
Cromossomos Humanos Y , Repetições de Microssatélites , Masculino , Humanos , Cazaquistão , Repetições de Microssatélites/genética , Cromossomos Humanos Y/genética , Polimorfismo Genético , Frequência do Gene , Genética Populacional , Haplótipos , ChinaRESUMO
Background and Objectives: Nowadays, every tenth adult in the world suffers from diabetes mellitus (DM). Diabetic retinopathy (DR) is the most common microvascular complication of type 2 DM (T2DM) and a leading cause of acquired blindness in middle-aged individuals in many countries. Previous studies have identified associations of several gene polymorphisms with susceptibility to microvascular complications of DM in various worldwide populations. In our study, we aimed to test the hypothesis of the associations of single nucleotide polymorphisms (SNP) of the VEGF (-2549I/D), RAGE (-429T/C and -374T/A), TCF7L2 (rs7903146), and ITGA2 (BglII) genes with a predisposition to DR among T2DM patients in the Kazakhstan population. Materials and Methods: We conducted a case-control study comparing the genotype distribution and allele frequencies between groups of DR patients (N = 94), diabetic patients without DR (N = 94), and healthy controls (N = 51). Genotypes were identified using the PCR-RFLP method. Results: In all cases, the genotype distribution corresponded to the Hardy-Weinberg equilibrium. The groups of diabetic patients with and without DR did not significantly differ in the genotype distribution of the SNPs studied. Differences between both groups of diabetic patients and healthy controls in four out of five SNPs were also not significant. At the same time, both groups of diabetic patients differed significantly from healthy controls in genotype distribution (p = 0.042 and 0.005, respectively) and allele frequencies (p = 0.021 and 0.002, respectively) of the BglII polymorphism in the ITGA2 gene. After adjusting for multiple comparisons, the differences between the group of diabetic patients without DR and the control group remained significant (pBonf = 0.027 for genotypes and pBonf = 0.009 for alleles). The BglII- allele was associated with diabetes: OR = 1.81 [1.09-2.99] for DR patients, and OR = 2.24 [1.34-3.75] for diabetic patients without DR. The association was also observed in the subset of Kazakhs. Conclusions: This study shows that the BglII polymorphism in the ITGA2 gene can be associated with T2DM but not with DR. According to our data, the risk allele for diabetes is the wild BglII- allele, and not the minor BglII+, which is considered as risky for DR.
Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Pessoa de Meia-Idade , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Estudos de Casos e Controles , Fator A de Crescimento do Endotélio Vascular , Cazaquistão/epidemiologia , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/genética , Frequência do Gene/genética , Polimorfismo de Nucleotídeo Único/genética , Genótipo , Predisposição Genética para Doença/genéticaRESUMO
Data on the genetic polymorphism of 27 Y-STR in Kazakhs of the Junior Zhuz has been presented and analyzed in relation to forensic features. A total of 464 representatives of the Western Kazakh tribes of Kazakhstan (Western Kazakhs, n = 405) and Uzbekistan (Karakalpakstan Kazakhs, n = 59) were examined by the Yfiler Plus set. The data are available in the YHRD under accession numbers YA006010 and YA006009. Genetic analysis (AMOVA and MDS) did not show significant differences between the two groups (Kazakhstan and Karakalpakstan Kazakhs) in terms of Y-chromosome diversity. Both groups are characterized by haplogroup C2a1a2 as a founder effect, which dominated two of the three tribes: Alimuly (67%), Baiuly (74.6%), and Zhetiru (25.8%). At the same time, the phylogenetic network for each tribe found its own clusters within C2a1a2. Western Kazakhs and Karakalpakstan Kazakhs present high values of unique haplotypes (84.44% and 96.61%), discrimination capacity (90.37% and 98.30%), and haplotype diversity (0.9991 and 0.9994). A set of 27 Y-STR loci distinguishes closely related individuals within the Western Kazakh tribes quite well. It is suitable for forensic application, and is also optimal for population genetics studies.
Assuntos
Cromossomos Humanos Y , Repetições de Microssatélites , Humanos , Cromossomos Humanos Y/genética , Genética Populacional , Filogenia , Cazaquistão , Uzbequistão , Polimorfismo Genético , ChinaRESUMO
The variability of nucleotide repeats is considered one of the causes of diseases, but their biological function is not understood. In recent years, the interaction of miRNAs and piRNAs with the mRNAs of genes responsible for developing neurodegenerative and oncological diseases and diabetes have been actively studied. We explored candidate genes with nucleotide repeats to predict associations with miRNAs and piRNAs. The parameters of miRNAs and piRNA binding sites with mRNAs of human genes having nucleotide repeats were determined using the MirTarget program. This program defines the start of the initiation of miRNA and piRNA binding to mRNAs, the localization of miRNA and piRNA binding sites in the 5'-untranslated region (5'UTR), coding sequence (CDS) and 3'-untranslated region (3'UTR); the free energy of binding; and the schemes of nucleotide interactions of miRNAs and piRNAs with mRNAs. The characteristics of miRNAs and piRNA binding sites with mRNAs of 73 human genes were determined. The 5'UTR, 3'UTR and CDS of the mRNAs of genes are involved in the development of neurodegenerative, oncological and diabetes diseases with GU, AC dinucleotide and CCG, CAG, GCC, CGG, CGC trinucleotide repeats. The associations of miRNAs, piRNAs and candidate target genes could be recommended for developing methods for diagnosing diseases, including neurodegenerative diseases, oncological diseases and diabetes.
Assuntos
MicroRNAs , Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas , Biologia Computacional/métodos , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Nucleotídeos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Repetições de TrinucleotídeosRESUMO
BACKGROUND: Previous studies of the genetic polymorphism of the Y-chromosome of Kazakhs were focussed on the Eastern, Central, Southern, and Western regions of Kazakhstan. In addition, many of these studies were limited to 17 Y-STR loci from the Yfiler. AIM: To enrich the existing Kazakhstan Y-chromosome Haplotype Reference Database from the Northern Kazakh population data by a wide set of 27 Y-STR and investigate the population genetic relationships with previously published data. SUBJECTS AND METHODS: Twenty-seven Y-STR loci from the Yfiler Plus PCR Amplification Kit were analysed in 382 healthy unrelated Kazakh males from Northern Kazakhstan. Genetic polymorphism was analysed using Arlequin software. RESULTS: A total of 326 distinct haplotypes of the 27 Y-STR loci were observed in 382 individuals. The discrimination capacity (0.9982) and haplotype diversity (0.8534) were computed. A total of 168 alleles at single-copy loci were observed and their frequencies ranged from 0.003-0.843. The pairwise genetic distance (RST) showed that the Northern Kazakh population is genetically distinct from the Chinese Kazakh population. CONCLUSIONS: Genetic polymorphism shows that the potential value of 27 Y-STR loci for forensic casework in the Northern Kazakh population and the current findings might be beneficial for paternal lineages in the study of population genetics.
Assuntos
Cromossomos Humanos Y , Repetições de Microssatélites , China , Cromossomos Humanos Y/genética , Genética Populacional , Haplótipos , Humanos , Cazaquistão , Masculino , Repetições de Microssatélites/genética , Polimorfismo GenéticoRESUMO
BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. At present, there is a need to search for new, accurate, reliable, minimally invasive and cheap biomarkers in addition to existing methods for the diagnosis and prognosis of BC. The main goal of this study was to test the diagnostic value of six circulating miRNAs in Kazakh women. MATERIALS AND METHODS: TaqMan-based miRNA profiling was conducted using plasma specimens from 35 BC women patients and 33 healthy women samples (control group). RESULTS: The level of all seven miRNAs (including endogenous control) normalized by synthetic cel-miR-39 were significantly elevated in the group of BC patients. Normalization using miR-222-3p as endogenous control reduced differences in level of miRNAs between groups; as a result, only three miRNAs were significantly upregulated in the group of BC patients-miR-145-5p (P = 6.5e-12), miR-191-5p (P = 3.7e-10) and miR-21-5p (P = 0.0034). Moreover, ROC analysis showed that the use of miR-145-5p and miR-191-5p, both individually (AUC = 0.931 and 0.904, respectively) or in combination (AUC = 0.984), allows to accurately differentiate BC patients from healthy individuals. CONCLUSIONS: Two plasma miRNAs-miR-145-5p and miR-191-5p-are potential biomarkers for diagnosis of BC in the Kazakh population. The findings need to be further substantiated using a more representative sample.