Hardy-Weinberg Research Articles

Association of Gene Variants for Mechanical and Metabolic Muscle Quality with Cardiorespiratory and Muscular Variables Related to Performance in Skiing Athletes.

Background: Skiing is a popular outdoor sport posing different requirements on musculoskeletal and cardiorespiratory function to excel in competition. The extent to which genotypic features contribute to the development of performance with years of ski-specific training remains to be elucidated. We therefore tested whether prominent polymorphisms in genes for angiotensin converting enzyme (ACE-I/D, rs1799752), tenascin-C (TNC, rs2104772), actinin-3 (ACTN3, rs1815739) and PTK2 (rs7460 and rs7843014) are associated with the differentiation of cellular hallmarks of muscle metabolism and contraction in high level skiers. Material & Methods: Forty-three skiers of a world-leading national ski team performed exhaustive cardiopulmonary exercise testing as well as isokinetic strength testing for single contractions, whereby 230 cardiopulmonary measurements were performed in the period from 2015–2018. A total of 168 and 62 data measurements were from the Alpine and Nordic skiing squads, respectively. Ninety-five and one hundred thirty-five measurements, respectively, were from male and female athletes. The average (±SD) age was 21.5 ± 3.0 years, height 174.0 ± 8.7 cm, and weight 71.0 ± 10.9 kg for the analysed skiers. Furthermore, all skiers were analysed concerning their genotype ACE-I/D, Tenascin C, ACTN3, PTK2. Results: The genotype distribution deviated from Hardy–Weinberg equilibrium for the ACTN3 genotype, where rs1815739-TT genotypes (corresponding to the nonsense mutation) were overrepresented in world-class skiers, indicating a slow muscle fibre phenotype. Furthermore, the heterozygous rs2104772-AT genotypes of TNC also demonstrated the best scaled peak power output values during ramp exercise to exhaustion. The highest values under maximum performance for heart rate were associated with the rs1799752-II and rs1815739-CC genotypes. The lowest values for peak power of single contractions were achieved for rs1815739-CC, rs1799752-II and rs7843014-CT genotypes. The skiing discipline demonstrated a main influence on cardiorespiratory parameters but did not further interact with genotype-associated variability in performance. Discussion: Classically, it is pointed out that muscles of, for example, alpine skiers do not possess a distinct fibre type composition, but that skiers tend to have a preponderance of slow-twitch fibres. Consequently, our findings of an overrepresentation of ACTN3-TT genotypes in a highly selective sample of elite world class skiers support the potential superiority of a slow fibre type distribution. Conclusions: We suggest that one competitive advantage that results from a slow, typically fatigue-resistant fibre type distribution might be that performance during intense training days is better preserved, whereby simply a higher technical training volume can be performed, yielding to a competitive advantage.

An association study of IL2RA polymorphisms with cerebral palsy in a Chinese population

BackgroundCerebral palsy (CP), the most common physical disability of childhood, is a nonprogressive movement disorder syndrome. Eighty percent of cases are considered idiopathic without a clear cause. Evidence has shown that cytokine abnormalities are widely thought to contribute to CP.MethodsAn association between 6 SNPs (rs12244380, rs2025345, rs12722561, rs4749926, rs2104286 and rs706778) in IL2RA (interleukin 2 receptor subunit alpha) and CP was investigated using a case–control method based on 782 CP cases and 778 controls. The allele, genotype and haplotype frequencies of SNPs were assessed using the SHEsis program. Subgroup analyses based on complications and clinical subtypes were also conducted.ResultsGlobally, no differences in genotype or allele frequencies for any SNPs remained significant after Bonferroni correction between patients and controls, except rs706778, which deviated from Hardy–Weinberg equilibrium and was excluded from further analyses. However, subgroup analysis revealed a significant association of rs2025345 with spastic tetraplegia (P genotype = 0.048 after correction) and rs12722561 with CP accompanied by global developmental delay (P allele = 0.045 after correction), even after Bonferroni correction.ConclusionsThese findings indicated that genetic variations in IL2RA are significantly associated with CP susceptibility in the Chinese Han population, suggesting that IL2RA is likely involved in the pathogenesis of CP. Further investigation with a larger sample size in a multiethnic population is needed to confirm the association.

Comment on three papers about Hardy-Weinberg equilibrium tests in autopolyploids.

Comment on three papers about Hardy-Weinberg equilibrium tests in autopolyploids.

Association between vitamin D receptor gene polymorphism and essential hypertension: a systematic review and meta-analysis

Abstract Background and aim Recent publications reported that the association between Vitamin D Receptor (VDR) gene polymorphism of Fokl (rs228570 or rs10735810) and essential hypertension (EH) remains controversial. Thus, we conducted this study to investigate the relationship between Fokl and EH. Methods Major medical databases (EMBASE, PUBMED, Science Direct, Cochrane, Springer, Scopus, ProQuest, and Lilacs) were systematically searched for observational studies evaluating the impact of Fokl polymorphism on EH, published until January 2022 with predefined protocol and without language restriction regarding PRISMA guideline. Analysis was performed in RevMan 5.3 (fixed and random-effects model through heterogeneity test) to provide pooled measures for odds ratio (OR) under Hardy-Weinberg Equilibrium based-on allele contrast, additive, dominant, and recessive genetic models. Results Eight observational studies enrolled comprising 3,762 cases and 4,445 controls. Under the allele model, Fokl polymorphism (f vs F) significantly increased the odds of having EH (OR=1.27; 95% confidence interval: 1.05–1.53), p=0.01. Fokl polymorphism was not significantly associated with EH under additive model (ff vs FF) with OR=0.94 (0.57–1.54), p=0.79, dominant model (Ff + ff vs FF) with OR=0.97 (0.8–1.16), p=0.76 and recessive model (FF + Ff vs ff) with OR=0.96 (0.59–1.56), p=0.97 However, subgroup analysis based on ethnicities, comprising Asian, European, American, and African, showed that only in African population, Fokl polymorphism was associated with reduced odds of EH under additive (OR=0.36; 0.17–0.74), p=0.005 and recessive model (OR=0.31; 0.14–0.7), p=0.005. Conclusions VDR gene polymorphism of Fokl was significantly associated with EH in a particular genetic model and could be affected by ethnicity. However, further studies are needed to make the robust evidence. Funding Acknowledgement Type of funding sources: None.

Characteristic of the uncontrolled hypertension course in patients of the aral sea region with uncomplicated hypertensive crisis

Abstract Purpose To study the features of the course of uncontrolled arterial hypertension (AH) in the Aral Sea region with the identification of the prevalence of various genotypes of the angiotensinogen (AGT) gene in patients with uncomplicated hypertensive crisis. Methods The genetic part included 94 patients with uncomplicated hypertensive crisis, an average age of 55.3±8.6 years, 54 (58.3%)women and 40 men (41.7%). The control group consisted of 50 healthy women and men, an average age of 52.7±6.4 years in equal proportion. The genetic study was carried out by real-time PCR with the determination of the prevalence of genotypes and alleles of genetic polymorphisms AGT 521 C>T, AGT 704 T>C. Results Patients with uncomplicated hypertensive crisis were characterized by LV hypertrophy, thickening of the intima-media thickness of the common carotid artery, and kidney damage. Henken's test showed that patients with AH require a significantly higher concentration of table salt to determine the threshold of taste sensitivity than in the control group: 0.51±0.17% versus 0.21±0.14% concentration of NaCl. The distribution of 704T>C genotypes of the AGT gene polymorphism was as follows: CC genotype 43.6%, CT genotype 45.8%, TT genotype 10.6% of cases, χ2=32.777, p=0.000; C allele – 66.5%, T allele - 33.5% of cases, χ2=40.894, p=0.000. Among healthy individuals, the distribution by genotypes showed a significant predominance of the CC genotype: CC 76%, CT 24%, TT genotype was not detected in the presented sample, χ2=67.92, p=0.000; C-allele 88%, T-allele 12%, χ2=115.52, p=0.000. The above data of the group of patients and healthy people corresponded to the theoretical Hardy-Weinberg equilibrium. The distribution of 521T>C genotypes of the AGT gene polymorphism among AH patients was as follows: CC genotype – 79.8%, CT genotype – 16%, TT genotype – 4.2% of cases, χ2=139.8, p=0.000; C-allele – 87.8%, T-allele – 12.2%, χ2=214.5, p=0.000. Among healthy individuals, a significant predominance of the CT genotype was shown: CC genotype – 40%, CT genotype – 60% of cases, χ2=42.0, p=0.000; C-allele – 70%, T-allele – 30%, χ2=32.0, p=0.000. The above data of the group of patients and healthy people did not correspond to the theoretical Hardy-Weinberg equilibrium Conclusion Patients with uncomplicated hypertensive crisis, living in the aral sea region, are characterized by severe damage of target organs, a high threshold of taste sensitivity to table salt. Based on genetic models of inheritance, a significant prevalence of the C-allele and CC genotype 704 T>C AGT gene polymorphism in healthy individuals was revealed, which characterizes the C-allele and CC genotype as protective against AH in people of the Aral Sea region. Significantly greater accumulation of the C-allele 521 C>T polymorphism of the AGT gene among AH patients is a factor of predisposition to a complicated course of AH in people of the aral sea region. Funding Acknowledgement Type of funding sources: None.

The phenotypes and alleles frequencies of ABO blood groups in Western Uganda

ABO blood group system is one of the clinically significant blood classification systems that vary across populations. Knowledge of distribution of the ABO blood system can help us to predict herd immunity and transmissibility of a disease in a population. In Uganda, little was known about this system and no research had been carried out to elaborate on the distribution of the A, B, AB and O blood types. Therefore, a cross-sectional study was conducted among people ≥12 years attending Buhinga hospital in Western Uganda from April to June 2019 to determine the phenotypes and alleles frequencies of the A, B, AB and O blood groups. Participants were recruited by simple random sampling technique and demographic data was obtained. 379 venous blood samples were collected and tested for ABO sero-types. Phenotypic data was analyzed using descriptive statistics, chi-square test of association and Hardy-Weinberg law of computation. Frequencies of ABO phenotypes were in the following order; O (39.8%)>, A (39.6%) >, B (12.4%)> AB (8.2%). There was no significant difference in the A, B, AB and O phenotype frequencies between males and females (p-value= 0.91). Based on Hardy-Weinberg Law, frequencies of the A, B, O alleles were; 0.63 for the O allele, 0.27 allele for the A allele and 0.14 for the B allele. Predominance of blood group O is more likely to influence population immunity.

HTRA1 rs11528744, BCRA1 rs9928736, and B3GLCT rs4381465 are associated with age-related macular degeneration in a Chinese population.

Purpose: Age-related macular degeneration (AMD) is a leading cause of vision loss. A Previous study based on the co-localization analysis of the genome-wide association study (GWAS) and eQTL genetic signals have reported that single nucleotide polymorphisms (SNPs), including rs760975, rs11528744, rs3761159, rs7212510, rs6965458, rs7559693, rs56108400, rs28495773, rs9928736, rs11777697, rs4381465 are associated with AMD in Americans. The aim of this study was to investigate the association of these SNPs in a Han Chinese population. Methods: There were 576 patients with wet AMD and 572 healthy controls collected in this study. All SNPs were genotyped by flight mass spectrum. Hardy–Weinberg equilibrium was applied to evaluate allele distributions for both AMD and control groups. The genotype and allele frequencies were evaluated using the χ2 tests. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated for the risk of genotype and allele. Results: Three of the 11 SNPs (rs11528744 in HTRA1, rs9928736 in BCRA1 and rs4381465 in B3GLCT) were found to be significantly associated with AMD in the allelic model (corrected p = 0.001, OR = 1.391, 95%CI = 1.179–1.640 for rs11528744; corrected p = 0.004, OR = 0.695, 95%CI = 0.544–0.888 for rs9928736; corrected p = 0.002, OR = 0.614, 95%CI = 0.448–0.841 for rs4381465). There were no differences for the remaining eight SNPs between AMD cases and healthy controls. Conclusion: Our results showed that HTRA1 rs11528744, BCRA1 rs9928736, and B3GLCT rs4381465 were associated with wet AMD, suggesting that HTRA1, BCRA1, and B3GLCT genes may be involved in the development of AMD.

Study of interactions between CFH gene polymorphism and retinal pigment epithelium phenotype in age-related macular degeneration

Annotation. AMD (age-related macular degeneration) is one of the leading causes of blindness in the world, associated with the formation of extracellular deposits called drusen in the macula, i.e. in the central part of the retina. These drusen contain cellular debris and proteins, including components of the complement system, such as the regulator CFH (complement factor H). Complement dysregulation is believed to play a major role in the development of AMD. CFH acts through its ability to recognize polyanionic structures (eg, sulfated GAGs (glycosaminoglycans)) found in host tissues, and thus CFH inactivates any complement system (C3b) that is deposited. Importantly, the common CFH (Y402H) polymorphism was strongly associated with an increased risk of AMD. Recent studies have shown that the disease-associated allotype 402H interacts more poorly (compared to 402Y) with binding sites in the macula (eg, Bruch's membrane), where GAGs (glycosaminoglycans), heparan sulfate, and dermatan sulfate play a major role in mediating the interaction with CFH. Decreased binding of the 402H allotype may lead to complement dysregulation, leading to chronic local inflammation that may contribute to drusen accumulation and thus the initiation, development, and progression of AMD. That is why the goal of our study was to highlight the effect of the rs1061170 polymorphism of the CFH gene on the occurrence and development of age-related macular degeneration and to clarify the intensity of this pathological effect. The study group consisted of 291 people suffering from AMD (89 – with the “dry” form, 97 – with the “wet” form), the comparison group – 105 people without a history of ophthalmic pathology of the corresponding age. Optical coherence tomography (SOCT Copernicus “Optopol”) of the macular area of the retina was used in the study. We used the parameter ILM-RPE (internal limiting membrane-retinal pigmented epithelium). DNA was isolated from the biological material obtained by the buccal scraping method using the Bio-Rad Chelex ® 100 kit. Polymerase chain reaction was used to detect the rs1061170 polymorphism of the CFH gene. Statistical processing of the obtained results was carried out using Statistica 10 (StatSoft, Inc., USA) and SPSS 23.0 programs. The following were used: Hardy-Weinberg equilibrium (Hardy–Weinberg); Kruskal-Wallis test ANOVA by Ranks and Friedman ANOVA and Kendall Coeff. of Concordance; H-criterion; indicators of the odds ratio (OR; Odds Ratio – OR) and 95% probable interval (±95% CI; Confidence limit for means Interval – CI); used the method of analysis of operating characteristic curves (ROC – Receiver Operating Characteristic curve analysis); used special formulas using 2x2 tables. Our results confirm the high prognostic significance of the rs1061170 polymorphism of the CFH gene on the development and progression of AMD in the Ukrainian population. Indicators of specificity and sensitivity of SNP genotypes are ambiguous.

Population structure of Caspian Kutum (Rutilus frisii, Nordmann, 1840) in the southern coast of Caspian Sea using Genome-wide single nucleotide polymorphism markers

The Caspian kutum (Rutilus frisii, Nordmann, 1840) is one of the most important semi-anadromous endemic fish species in the southern part of the Caspian Sea. The fisheries from wild populations of R. frisii are declined drastically due to variability of sea levels, overfishing, and illegal fishing. For this regard, genetic studies is very noticed to maintain of remained this endangered species. Here, we used restriction site-associated DNA sequencing (RAD-seq) approach to explore population structure, genetic variability, and single nucleotide polymorphisms (SNPs) from 146 individuals from eight rivers in Iran. In total 86,274 SNP loci were determined, and after filtering, 16,193 high-quality SNP markers were applied in statistical analyses. Twenty-eight percent of selected SNPs were located in genic regions and about 65% of these SNPs were in the coding sequence. Of the 102 SNP loci, 42 loci were found to be polymorphic and bi-allelic. The minor allele frequency (MAF) of these SNPs varied from 0.156 to 0.471. The observed heterozygosity (Ho) per locus ranged from 0.119 to 0.864, while the expected heterozygosity (He) per locus was from 0.142 to 0.569. Among these SNP loci, 22 SNP loci were significantly deviated from the Hardy–Weinberg equilibrium (P < 0.01) after Bonferroni correction. Both Principal coordinate analysis (PCA) and Bayesian clustering satisfyingly showed population genomic structure in Caspian kutum populations, indicating the description of distinct population segments. The first development of SNP markers in this study provides the better monitoring of population genetic variation in Caspian kutum at a more detailed level and in the scarce of genetic information about this species.

Impact of Methionine Synthase Reductase Polymorphisms in Chronic Myeloid Leukemia Patients.

Highlights What are the main findings? Our objective was to determine the relationship between the methionine synthase reductase polymorphisms (MTRR and MTR) and the risk of developing chronic myeloid leukemia (CML) in Sudanese Patients. What is the implication of the main finding? Here, we report that the heterozygous and homozygous mutant genotypes of MTRR polymorphisms were associated with a decreased risk of developing CML in the Sudanese population asa protective factor.Our findings will help to increase the understanding of MTRR A66G polymorphism and its association with CML risk in the Sudanese population. Introduction： Metabolism methionine and of folate play a vital function in cellular methylation reactions, DNA synthesis and epigenetic process.However, polymorphisms of methionine have received much attention in recent medical genetics research. Objectives: To ascertain whether the common polymorphisms of the MTRR (Methionine Synthase Reductase) A66G gene could play a role in affecting susceptibility to Chronic Myeloid Leukemia (CML) in Sudanese individuals. Methods: In a case-controlled study, we extracted and analyzed DNA from 200 CML patients and 100 healthy control subjects by the PCR-RFLP method. Results: We found no significant difference in age orgender between the patient group and controls. The MTRR A66G genotypes were distributed based on the Hardy-Weinberg equilibrium (p > 0.05). The variation of MTRR A66G was less significantly frequent in cases with CML (68.35%) than in controls (87%) (OR = 0.146, 95% CI = 0.162–0.662, p < 0.002). Additionally, AG and GG genotypes and G allele were reducing the CML risk (Odds ratio [OR] = 0.365; 95% CI [0.179–0.746]; p = 0.006; OR = 0.292; 95% CI [0.145–0.590]; p = 0.001 and OR = 0.146; 95% CI [0.162–0.662]; p = 0.002 and OR = 2.0; 95% CI [1.3853–2.817]; respectively, (p = 0.000)). Conclusions: Our data demonstrated that heterozygous and homozygous mutant genotypes of MTRR polymorphisms were associated with decreased risk of developing CML in the Sudanese population.

The application of short and highly polymorphic microhaplotype loci in paternity testing and sibling testing of temperature-dependent degraded samples.

Paternity testing and sibling testing become more complex and difficult when samples degrade. But the commonly used genetic markers (STR and SNP) cannot completely solve this problem due to some disadvantages. The novel genetic marker microhaplotype proposed by Kidd’s research group combines the advantages of STR and SNP and is expected to become a promising genetic marker for kinship testing in degraded samples. Therefore, in this study, we intended to select an appropriate number of highly polymorphic SNP-based microhaplotype loci, detect them by the next-generation sequencing technology, analyze their ability to detect degraded samples, calculate their forensic parameters based on the collected 96 unrelated individuals, and evaluate their effectiveness in paternity testing and sibling testing by simulating kinship relationship pairs, which were also compared to 15 STR loci. Finally, a short and highly polymorphic microhaplotype panel was developed, containing 36 highly polymorphic SNP-based microhaplotype loci with lengths smaller than 100 bp and A e greater than 3.00, of which 29 microhaplotype loci could not reject the Hardy-Weinberg equilibrium and linkage equilibrium after the Bonferroni correction. The CPD and CPE of these 29 microhaplotype loci were 1-2.96E-26 and 1-5.45E-09, respectively. No allele dropout was observed in degraded samples incubated with 100°C hot water for 40min and 60min. According to the simulated kinship analysis, the effectiveness at the threshold of 4/−4 reached 98.39% for relationship parent-child vs. unrelated individuals, and the effectiveness at the threshold of 2/−2 for relationship full-sibling vs. unrelated individuals was 93.01%, which was greater than that of 15 STR loci (86.75% for relationship parent-child vs. unrelated individuals and 81.73% for relationship full-sibling vs. unrelated individuals). After combining our 29 microhaplotype loci with other 50 short and highly polymorphic microhaplotype loci, the effectiveness values at the threshold of 2/−2 were 82.42% and 90.89% for relationship half-sibling vs. unrelated individuals and full-sibling vs. half-sibling. The short and highly polymorphic microhaplotype panel we developed may be very useful for paternity testing and full sibling testing in degraded samples, and in combination with short and highly polymorphic microhaplotype loci reported by other researchers, may be helpful to analyze more distant kinship relationships.

Effect of APOB gene polymorphisms on body mass index, blood pressure, and total cholesterol levels: A cross-sectional study in Mexican population.

APOB gene polymorphisms are considered risk factors for the development of dyslipidemia, hypertension, and cardiovascular disease (CVD) in several populations. In Mexico, these pathologies are frequent and studies regarding this gene are scarce. The aim of this cross-sectional study was to determined genotype, allele, and haplotype frequencies of APOB polymorphisms and performed analyses of association among the biochemical, hemodynamic, anthropometrical, and genetic variables. Blood samples were taken from 361 subjects from unselected Mexican population for biochemical analysis and for deoxyribonucleic acid extraction; besides blood pressure and body mass index (BMI) were measured. APOB polymorphisms rs934197, rs533617, rs693, and rs1042031 were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism; whereas, rs17240441 and c.66_67insCTGCTG were genotyped by PCR followed by electrophoresis. Genotype and allele frequencies were obtained by simple counting and deviations from Hardy-Weinberg equilibrium (HWE) were calculated by chi-square test. The effect of the polymorphisms on the quantitative variables was determined using analysis of variance, Student’s t test, Pearson’s and Spearman’s correlations and multiple linear regression models. All the polymorphisms were within HWE. Frequencies of mutated alleles were highly heterogeneous: rs934197-T 33.6%, rs17240441-D 39.3%, c.66_67insCTGCTG-I 3.9%, rs533617-G 0.9%, rs693-T 40.5%, and rs1042031-G 17.3%. Chronic degenerative diseases were frequent in the studied population: overweight-obesity 55.1%, dyslipidemia 45.8%, and hypertension 23.5%. The association analyses showed that despite adjustments for age and sex the mutated alleles rs934197-T, rs1042031G, c.66_67-insCTGCTG-I, and rs533617-G, were related to lower values of BMI, total cholesterol (TC), systolic blood pressure, and diastolic blood pressure, respectively. All polymorphisms analyzed except rs533517 and c.66_67insCTGCTG showed high frequencies of the mutated allele, making them useful for association studies. Our results revealed that, APOB gene polymorphisms could be contributing to the development of several chronic diseases, such as essential hypertension, dyslipidemias, obesity, among others. However, specific studies with each pathology are needed to know the possible implications of the polymorphisms.

Breaking the reproductive barrier of divergent species to explore the genomic landscape.

Background: Climate change will have significant consequences for species. Species range shifts induce the emergence of new hybrid zones or the spatial displacement of pre-existing ones. These hybrid zones may become more porous as alleles are passed from one species to another. Currently, hybridization between highly divergent species living in sympatry seems extremely limited. Indeed, this phenomenon involves breaking two barriers. The first is the pre-mating barrier, related to the reproductive phenology of the two species. The second is the post-zygotic barrier, related to the genetic divergence between these species. Here, we were interested in identifying new hybridization patterns and potential implications, especially in the context of environmental modifications. Methods: We sampled Telestes souffia and Parachondrostoma toxostoma wild specimens from different locations across France and genotyped them for SNP markers. We identified discriminant loci using F1-hybrid specimens and parental species and performed principal component analysis and Bayesian model-based clustering to analyze phylogenetic information. Furthermore, we assessed deviation in allele frequency from F1 to F2 and for Hardy–Weinberg equilibrium for F2 and assessed gene function associated with two F2 cohorts. Results: We demonstrate that by breaking the ecological barrier, massive introgressive hybridization is possible between two endemic lineages of Cyprinidae belonging to two distinct genera. For both cohorts studied (=2 cm and >2 cm), a large majority of loci (>88%) presented no deviation in allele frequency and no departure from the Hardy–Weinberg equilibrium. For individuals beyond the 2 cm stage, two phenomena were observed. The first was an allelic imbalance in favor of P. toxostoma, for some genomic regions, with genes involved in developmental regulatory processes, cytoskeletal organization, and chromosome organization. The second was an excess of heterozygous loci coupled with an equilibrium of allelic frequencies for genes involved in immune response and kidney/liver development. Moreover, the 2 cm-sized specimens with high mortality yielded a particular genomic signature. Conclusion: Our study displayed important results for understanding the early stages of hybridization between divergent lineages and predicting the emergence of future hybrid zones in the wild. Moreover, this hybridization generates a wide spectrum of hybrids that are a potential source of important evolutionary novelties.

SCN1A polymorphisms influence the antiepileptic drugs responsiveness in Jordanian epileptic patients.

The aim of this study was to evaluate whether the voltage-gated sodium channel alpha subunit 1 (SCN1A) gene polymorphisms influence the responsiveness of Jordanian epileptic patients to antiepileptic drugs (AEDs). A total of 72 AEDs-treated epileptics were polymerase chain reaction (PCR)-genotyped for six single nucleotide polymorphisms (SNPs), including SCN1A rs2298771, rs3812718, rs3812719, rs2217199, rs2195144 and rs1972445. Genotype and allele distributions in drug-responsive and drug-resistant patients were compared. The six SNPs haplotypes were examined, and the linkage disequilibrium (LD) was assessed. The genotypes of drug-resistant and drug-responsive groups were in Hardy-Weinberg equilibrium. Three genetic polymorphisms of the SCN1A gene seemed to influence the resistance to AEDs, on the level of alleles and genotypes. Data revealed that rs2298771 G allele, rs3812719 C allele, and rs2195144 T allele increased the risk of developing AEDs-resistance (OR=2.9; 95%CI= 1.4-5.9, p=0.003; OR=2.4; 95%CI=1.2-4.7, p=0.01; OR=2.3; 95%CI=1.2-4.7, p=0.01), respectively. Haplo type analysis of SCN1A polymorphisms revealed high-degree LD associated with resistance to AEDs. A synergetic effect appears with highly significant association in GCCATG haplotype of rs2298771, rs3812718, rs3812719, rs2217199, rs2195144, and rs1972445 respectively (OR=2.8; 95%CI=1.5-6.2, p=0.002). Data suggests that SCN1A polymorphisms could influence the resistance to AEDs in Jordanian epileptics at three SNPs (rs2298771; rs3812719; rs2195144). Additionally, haplotype analysis indicated a substantial degree of LD between the six SCN1A polymorphisms. Further investigation with larger sample size is needed to confirm the results of the current study.

Correlation research of susceptibility single nucleotide polymorphisms and the severity of clinical symptoms in attention deficit hyperactivity disorder.

ObjectiveTo analyze the correlation between susceptibility single nucleotide polymorphisms (SNPs) and the severity of clinical symptoms in children with attention deficit hyperactivity disorder (ADHD), so as to supplement the clinical significance of gene polymorphism and increase our understanding of the association between genetic mutations and ADHD phenotypes.Methods193 children with ADHD were included in our study from February 2017 to February 2020 in the Children’s ADHD Clinic of the author’s medical institution. 23 ADHD susceptibility SNPs were selected based on the literature, and multiple polymerase chain reaction (PCR) targeted capture sequencing technology was used for gene analysis. A series of ADHD-related questionnaires were used to reflect the severity of the disease, and the correlation between the SNPs of specific sites and the severity of clinical symptoms was evaluated. R software was used to search for independent risk factors by multivariate logistic regression and the “corplot” package was used for correlation analysis.ResultsAmong the 23 SNP loci of ADHD children, no mutation was detected in 6 loci, and 2 loci did not conform to Hardy-Weinberg equilibrium. Of the remaining 15 loci, there were 9 SNPs, rs2652511 (SLC6A3 locus), rs1410739 (OBI1-AS1 locus), rs3768046 (TIE1 locus), rs223508 (MANBA locus), rs2906457 (ST3GAL3 locus), rs4916723 (LINC00461 locus), rs9677504 (SPAG16 locus), rs1427829 (intron) and rs11210892 (intron), correlated with the severity of clinical symptoms of ADHD. Specifically, rs1410739 (OBI1-AS1 locus) was found to simultaneously affect conduct problems, control ability and abstract thinking ability of children with ADHD.ConclusionThere were 9 SNPs significantly correlated with the severity of clinical symptoms in children with ADHD, and the rs1410739 (OBI1-AS1 locus) may provide a new direction for ADHD research. Our study builds on previous susceptibility research and further investigates the impact of a single SNP on the severity of clinical symptoms of ADHD. This can help improve the diagnosis, prognosis and treatment of ADHD.

DISTRIBUTION OF KCNJ11 RS5219 POLYMORPHISM IN VIETNAMESE POPULATION AND ITS ASSOCIATION WITH HYPERGLYCEMIA

Aims: KCNJ11 gene, encoding ATP-sensitive channel subunits, involves in insulin secretion. The study aimed at investigating the distribution of the KCNJ11 E23K (rs5219) polymorphism and its association with prediabetes and type 2 diabetes (T2D) in Vietnamese population. Methods: A cross-sectional study randomly recruited 2.676 participants aged 40-64 years from a general population in Ha Nam province, Vietnam. Glycemic status of the subjects was classified based on fasting plasma glucose and oral glucose tolerance test. PCR-restriction fragment length polymorphism method was applied to detect the KCNJ11-rs5219 polymorphism. Genotype frequencies were compared to find the distribution difference among normoglycemic, prediabetes, and T2D groups. Generalized linear models and multinomial logistic regression analysis were used to determine the associations of the KCNJ11-rs5219 polymorphism with prediabetes and T2D. Results: The frequencies of minor K allele in normoglycemic, prediabetes and T2D groups were 33.2, 32.6 and 35.4%, respectively. Genotype distribution of the E23K polymorphism was in Hardy-Weinberg equilibrium and not significantly different among the three glucose groups (p &gt; 0.05). Fasting plasma glucose and 2-h glucose levels were not significantly different among three genotypes EE, EK, and KK (p &gt; 0.05). After adjusted for social-economic status, lifestyle and clinical patterns, no significant association was found between the KCNJ11-rs5219 polymorphism and hyperglycemia with ORs from 0.80 to 1.29. Conclusions: The minor K allele was predominant and genotype frequency in the population was remained constant among generations. The study suggests no significant association between the KCNJ11-rs5219 polymorphism and hyperglycemia in the Vietnamese population.

Population Genetic Data of 30 Insertion-Deletion Markers in the Polish Population.

(1) Background: Insertion-deletion (InDel) markers show the advantages of both short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) and are considered alternative markers in forensic genetics. (2) Methods: Allelic frequencies and corresponding forensic efficiency parameters of 30 autosomal polymorphic InDel loci included in the Investigator DIPplex kit (Qiagen) were obtained in a sample of 631 unrelated Polish individuals. Allelic frequency data were compared with those reported for selected populations (3) Results: All the loci conformed with Hardy-Weinberg equilibrium after applying a Bonferroni correction and no pair-wise significant linkage disequilibrium was detected. (4) Conclusions: DIPplex Kit differences were high among populations worldwide. The InDel markers are highly discriminating for human identification purposes in the Polish population.

Association of gene polymorphism and cytokine content in the blood serum in children with allergic bronchial asthma

The study of genes controlling cytokine activities of is among important tasks when assessing predisposition and revealing pathogenetic links of initiation and course of clinical disorders. Aberrant production of cytokines and dysregulation of immune response may be considered genetic predictors associated with differentiation and functioning of T helpers, being of decisive importance in pathogenesis of pediatric allergic bronchial asthma. Our objective was to evaluation of associations between polymorphic genotypes and serum levels of cytokines of various T helper profiles in the children with allergic bronchial asthma.&#x0D; We have observed 175 children aged 3 to 11 years. Of them, we have examined 75 patients diagnosed with allergic bronchial asthma (ABA) as well as 100 healthy children matched for age and gender. All children underwent general clinical and allergological examination. The contents of cytokines attributed to Th1, Th2 and Th17 profiles were determined in blood serum by means of ELISA technique. DNA samples isolated from peripheral venous blood were used for molecular genetic analysis. Using allele-specific PCR technique, the following mutation points were investigated: IFN (T-874 A), IL-4 (C-589 T), IL-6 (C-174 G), IL-17A (G- 197 A), TNF (G-308 A). The analysis of distribution and occurrence of the cytokine gene polymorphisms was carried out, and the odds ratio of the disease risk were calculated. Statistical data processing was carried out using the program Statistica 10 by methods of descriptive, parametric and non-parametric statistics, comparison of unrelated groups was performed by qualitative characteristics of HardyWeinberg equilibrium, and with Chi-square test ( 2).&#x0D; These studies have revealed differences in patterns and occurrence of polymorphic genotypes associated with aberrant production of cytokines typical for various Th profiles among the children with allergic bronchial asthma. A comparative analysis of the mutant allele frequencies and cytokine genotypes of various Th profiles, along with determination of the cytokine contents in blood serum of children with allergic bronchial asthma revealed a predominance of homozygous IFN 874A, IL-4 589T, IL-6 174G, IL-17A 197A, and TNF 308A genotypes. Studies of gene polymorphisms, features of production and content of the cytokines specific for T helpers 1, T helpers 2, T helpers 17 profiles in bronchial asthma in the children revealed differences in distribution and occurrence of mutant alleles associated with aberrant cytokine production, variable risk of developing allergic pathology and development of the distinct disease phenotype.

Diversity of SNP c.795A&gt;G PLAG1 Gene and its Association to Birth Weight of Bali Cattle

PLAG1 gene is one of those that regulate growth and body size. Â This study aimedto look at the PLAG1 gene polymorphism and its relationship to birth weight in Bali cattle using PCR-RFLP. The total sample used was 104 samples consisting of 66 Bali cattle from BPTU-HPT Denpasar and 38 Bali cattle from BPT-HMT Serading, each of which had birth weight data. PLAG1 gene polymorphism was analyzed using PCR-RFLP and the Sac1 restriction enzyme. The genotype and allele frequencies, heterozygosity, and Hardy-Weinberg equilibrium were all examined using Popgen32. General Linear Model was used to analyze the association of SNP 795AG PLAG1 gene with birth weight in Bali cattle. Amplification of the PLAG1 gene resulted in 776 bp fragments and two alleles. The PLAG1 gene had three genotypes: AA (562 bp and 182 bp), AG (562 bp, 182 bp, and 104 bp), and GG (562 bp, 182 bp, and 104 bp). Based on the results, the PLAG1 gene in Bali cattle was polymorphic. The alleles frequency of Bali cattle wasin Hardy-Weinberg equilibrium. The SNP c.795AG PLAG1 gene genotype were associated with birth weight in Bali cattle. The A allele is a determinant of high birth weight in Bali cattle where the AG genotype has the highest birth weight.

Evaluation of the BMPR-1B gene functional polymorphisms and their association with litter size in Qinghai Tibetan sheep

The Bone morphogenetic protein receptor-1B (BMPR-1B) was one of the most major candidate gene for sheep follicular development and litter size trait. The BMPR-1B gene encoded a structural and functional highly conserved transmembrane protein related to sheep reproductive performance. To further validate its genetic effect, genotype-phenotype associations were performed in Tibetan sheep. Through DNA sequencing of the entire coding region of the BMPR-1B gene using DNA of 30 unrelated Tibetan ewes (10 Singletons Tibetan ewes, and 20 Twins Tibetan ewes). And genotyping the target SNPs loci using PCR-RFLP (or PCR-SSCP) combined with DNA sequencing and analyzing their association with lambing traits in 510 Tibetan ewes. One mutation in 3′UTR (A1354G) and three mutations in exons (G192A, A746G, T864C) were found to be strongly associated with lambing traits in Tibetan ewes in this study. χ2 suitability test showed that all of SNPs were Hardy-Weinberg equilibrium. After independence test, A746G, T864C and A1354G of BMPR-1B gene polymorphisms were significantly correlated with litter size in all-types of Tibetan sheep. These results indicate that the variations in the BMPR-1B genes and their corresponding genotypes may be considered as marker-assisted selection (MAS) for litter traits in Tibetan sheep breeding.