Significant Linkage Research Articles

Association between 5-HT1A receptor C-1019G, 5-HTTLPR polymorphisms and panic disorder: a meta-analysis.

HTR1A C-1019G polymorphism (rs6295) and serotonin transporter promoter polymorphism (5-HTTLPR) have been linked with panic disorder (PD) in different ethnic backgrounds. Both these polymorphisms are in the promoter regions. However, results are inconsistent and contrasting evidence makes reliable conclusions even more challenging. A meta-analysis was conducted to test whether C-1019G polymorphism and 5-HTTLPR were involved in the etiology of PD. Articles researching the link between C-1019G, 5-HTTLPR polymorphisms, and PD were retrieved by database searching and systematically selected on the basis of selected inclusion parameters. 21 studies were included that examined the relationship of rs6295,5-HTTLPR polymorphisms with PD risk susceptibility (rs62957 polymorphism - 7 articles, and 5-HTTLPR polymorphism - 14 articles). A significant association was seen between the rs6295 polymorphism and PD pathogenesis, especially in Caucasian PD patients. No significant genetic linkage was found between the 5-HTTLPR polymorphism and PD. C-1019G polymorphism was involved in the etiology of PD in Caucasian patients. The 5-HTTLPR polymorphism was not a susceptibility factor of PD.

Distribution of CYP3A4 and CYP3A5 Polymorphisms and Genotype Combination Implicated in Tacrolimus Metabolism.

Human cytochrome P450 (CYP), particularly CYP3A4 and CYP3A5 is mainly responsible for the metabolism of several drugs including tacrolimus. Significant interracial/interethnic variation in the expression and function of CYP3A5 and CYP3A4 is caused by Single Nucleotide Polymorphisms (SNPs) of genes encoding these proteins. The present study investigated the genetic polymorphisms CYP3A4*1B, CYP3A4*22, and CYP3A5*3 in the Tunisian population. We included in this study, Tunisian healthy subjects and renal transplant recipients receiving tacrolimus. CYP3A4 and CYP3A5 genotyping were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to the genotypic combination of the three CYP polymorphisms, we have identified for the first time four metabolizers statuses: slow metabolizers (SM), intermediate metabolizers (IM), high metabolizers (HM), and extensive metabolizers (EM). A total of 101 renal transplant patients and 102 healthy subjects were included. Our results showed that the predominant alleles in the Tunisian population are a wild type of CYP3A4*1B (0.87), likewise CYP3A4*22 (0.975) and CYP3A5*3 (0.82). The genotype frequencies of CYP3A4*1B, CYP3A4*22, and CYP3A5*3 were found to be 3.9%, 0.0%, and 69.5%, respectively. Also, we found a significant linkage disequilibrium between CYP3A4*1B and CYP3A5*3. We approved that the IM is the predominant phenotype in our population with 124 patients followed by and EM with 41 patients, HM in 29 patients and SM in 9 patients. These results showed that Tunisians are most similar to Caucasians. The genetic background of these enzymes CYP3A4*1B, CYP3A4*22, and CYP3A5*3 in this study are important in the prescription of personalized medicine.

The complete mitochondrial genome and microsatellite discovery of the Chilean kelp crab Taliepus dentatus (Brachuyra, Majoidea)

Abstract The complete sequence of the mitochondrial genome and fifteen microsatellite loci for the Chilean kelp crab Taliepus dentatus are reported for the first time. The DNA assembly obtained from an Illumina sequencing revealed a complete mitochondrial genome of 15 603 bp in length. The gene composition and arrangement were similar to that reported for most decapod crabs, containing 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and a non-coding region. A phylogeny performed with 10 species obtained from GenBank placed T. dentatus close to individuals of the Family Epialtidae. From the 6397 repeated sequences encountered in the data, 15 microsatellite loci primers were designed and five tested for variability in specimens obtained from two sampling sites separated by 300 km of distance. The mean number of alleles per locus was nine (5–15 alleles per locus) and the observed heterozygosities ranged from 0.34 to 0.8. Departure from Hardy–Weinberg equilibrium was observed in two out of the five microsatellites, while none of the loci exhibited significant linkage disequilibrium. This genetic resource will be useful for phylogeny, population genetics and parentage analysis of the commercial species T. dentatus.

Etiology, risk factors and antibiotic resistance in neonatal sepsis.

Objective: To determine the etiology, risk factors and antibiotic resistance in neonatal sepsis. Study Design: Cross-sectional study. Setting: Department of Pediatric Medicine, National Institute of Child Health, Karachi, Pakistan. Period: October 2023 to March 2024. Methods: A total of 174 neonates of both genders, with suspected neonatal sepsis were analyzed. Neonatal and maternal characteristics were noted. Blood sample was collected in aseptic environment and sent to institutional laboratory for blood culture and drug susceptibility testing. Results: In a total of 174 neonates, 101 (58.0%) were boys. The mean age, and weight were 9.61±7.86 years, and 2.25±0.85 kg, respectively. Neonatal sepsis on the basis of positive blood culture was reported in 38 (21.8%) neonates. Preterm birth had significant association with neonatal sepsis (44.7% vs. 26.5%, p=0.019). History of maternal UTI during pregnancy had significant linkage with neonatal sepsis (36.8% vs. 11.0%, p<0.001). History of maternal fever during pregnancy had statistically significant association with neonatal sepsis (34.2% vs/ 19.1%, p=0.049). E. Coli, and Klebsiella were the most commonly found bacterial isolates, noted in 8 (21.1%), and 4 (10.5%) neonates, respectively. Most commonly used antimicrobial drugs were found to have high resistance rates against most frequent bacterial isolates. Conclusion: E. Coli, and Klebsiella were the most commonly found bacterial isolates in neonatal sepsis. Preterm birth, maternal history of UTI, and maternal history of fever were found to be significant factors linked to neonatal sepsis. Most commonly used antimicrobial drugs were found to have high resistance patterns which should raise alarms.

Extensive genetic diversity in Plasmodium vivax from Sudan and its genetic relationships with other geographical isolates

Plasmodium vivax, traditionally overlooked has experienced a notable increase in cases in East Africa. This study investigated the geographical origin and genetic diversity of P. vivax in Sudan using 14 microsatellite markers. A total of 113 clinical P. vivax samples were collected from two different ecogeographical zones, New Halfa and Khartoum, in Sudan. Additionally, 841 geographical samples from the database were incorporated for a global genetic analysis to discern genetic relationships among P. vivax isolates on regional and worldwide scales. On the regional scale, our findings revealed 91 unique and 8 shared haplotypes among the Sudan samples, showcasing a remarkable genetic diversity compared to other geographical isolates and supporting the hypothesis that P. vivax originated from Africa. On a global scale, distinct genetic clustering of P. vivax isolates from Africa, South America, and Asia (including Papua New Guinea and Solomon Island) was observed, with limited admixture among the three clusters. Principal component analysis emphasized the substantial contribution of African isolates to the observed global genetic variation. The Sudanese populations displayed extensive genetic diversity, marked by significant multi-locus linkage disequilibrium, suggesting an ancestral source of P. vivax variation globally and frequent recombination among the isolates. Notably, the East African P. vivax exhibited similarity with some Asian isolates, indicating potential recent introductions. Overall, our results underscore the effectiveness of utilizing microsatellite markers for implementing robust control measures, given their ability to capture extensive genetic diversity and linkage disequilibrium patterns.

HINT1 Gene Polymorphisms, Smoking Behaviour, and Personality Traits: A Haplotype Case-Control Study.

The factors influencing the development and maintenance of nicotine dependence are numerous and complex. Recent studies indicate that smokers exhibit distinct genetic predispositions to nicotine dependence. We aimed to analyse (1) the association between rs2551038 and cigarette smoking, (2) the association of between the rs3864236-rs2526303-rs2551038 haplotype and cigarette smoking, and (3) the personality traits measured by the NEO Five-Factor Inventory in cigarette users and never-smokers. No significant differences were present in the frequency of rs2551038 genotypes and alleles in the studied cigarette users compared to the control group. Cigarette users, compared to the control group, had higher scores on the NEO-FFI Extraversion scale (p = 0.0011), and lower scores were obtained by the cigarette users for the NEO-FFI Openness (p = 0.0060), Agreeability (p ≤ 0.000), and Conscientiousness (p ≤ 0.000) scales. There was a significant positive Pearson's linear correlation between the age and the Fagestrom test (r = 0.346; p < 0.0001) and the NEO-FFI Openness scale (r = 0.180; p < 0.0001) in the group of cigarette users. We observed significant linkage disequilibrium between rs2526303 and rs3864236 (D' = 0.3581; p < 2.2204 × 10-16) and between rs2526303 and rs2551038 (D' = 0.9993; p < 2.2204 × 10-16) in the tested sample. The sex-stratified haplotype analysis revealed that in the group of male never-smokers, the GTC haplotype was significantly more frequent than in the group of cigarette users (38% vs. 22%; p = 0.0039). The presented study reveals significant differences in personality trait scores between cases and controls. Moreover, the sex-stratified analysis showed significant differences in haplotype distribution. These results underscore the interplay between genetic predisposition, sex, and personality in nicotine-using individuals.

"Filler-Associated Acute Stroke Syndrome": Classification, Predictive Modelling of Hyaluronidase Efficacy, and Updated Case Review on Neurological and Visual Complications.

The rising use of soft tissue fillers for aesthetic procedures has seen an increase in complications, including vascular occlusions and neurological symptoms that resemble stroke. This study synthesizes information on central nervous system (CNS) complications post-filler injections and evaluates the effectiveness of hyaluronidase (HYAL) treatment. A thorough search of multiple databases, including PubMed, EMBASE, Scopus, Web of Science, Google Scholar, and Cochrane, focused on publications from January 2014 to January 2024. Criteria for inclusion covered reviews and case reports that documented CNS complications related to soft tissue fillers. Advanced statistical and computational techniques, including logistic regression, machine learning, and Bayesian analysis, were utilized to dissect the factors influencing therapeutic outcomes. The analysis integrated findings from 20 reviews and systematic analyses, with 379 cases reported since 2018. Hyaluronic acid (HA) was the most commonly used filler, particularly in nasal region injections. The average age of patients was 38, with a notable increase in case reports in 2020. Initial presentation data revealed that 60.9% of patients experienced no light perception, while ptosis and ophthalmoplegia were present in 54.3 and 42.7% of cases, respectively. The statistical and machine learning analyses did not establish a significant linkage between the HYAL dosage and patient recovery; however, the injection site emerged as a critical determinant. The study concludes that HYAL treatment, while vital for managing complications, varies in effectiveness based on the injection site and the timing of administration. The non-Newtonian characteristics of HA fillers may also affect the incidence of complications. The findings advocate for tailored treatment strategies incorporating individual patient variables, emphasizing prompt and precise intervention to mitigate the adverse effects of soft tissue fillers. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Impulsivity and self-harm behavior in patients with synthetic cannabinoids dependence

Background Synthetic cannabinoids (SCs) dependence is increasingly prevalent among young individuals globally, with limited understanding of their potential detrimental effects. Therefore, we conducted this comparative study to assess impulsivity and non-suicidal self-harm behavior in patients with SCs dependence. Subjects and method We conducted this comparative, case-control study in the outpatient clinics of (Beni-suef University Hospital). We recruited 30 patients with SCs dependence and the 30 healthy subjects as a control group. Psychometric scales, including Addiction Severity Index (ASI), Barratt Impulsivity Scale-11 (BIS-11), Deliberate Self-harm Inventory-Short Version (DSHI), SCID I, SCID II, and drug urine screen, were applied to compare the two study arms. Results DSHI-s scores were significantly higher between the two study arms (3.23 ± 4.97 vs. 0.0 ± 0.0, p < 0.001, for cases and controls, respectively). Similarly, the mean ± SD score of the BIS scale was significantly higher in cases 68.13 ± 9.75 compared to the control group (45.67 ± 5.12) with a statistically significant difference (p < 0.001). Using the regression analysis, we observed a significant positive linkage between age, duration of substance use, DSHI-s, and the Barratt scale. Conclusion Patients with synthetic cannabis addiction exhibited more impulsivity and self-harm behaviors compared to healthy controls. The adverse effects of substance use disorder escalated, notably in individuals classified as having severe addiction based on the Addiction Severity Index. Age and length of substance use were found to be potential factors influencing the level of impulsivity and self-harm actions.

FBLN2 is associated with Goldenhar syndrome and is essential for cranial neural crest cell development.

Goldenhar syndrome, a rare craniofacial malformation, is characterized by developmental anomalies in the first and second pharyngeal arches. Its etiology is considered to be heterogenous, including both genetic and environmental factors that remain largely unknown. To further elucidate the genetic cause in a five-generation Goldenhar syndrome pedigree and exploit the whole-exome sequencing (WES) data of this pedigree, we generated collapsed haplotype pattern markers based on WES and employed rare variant nonparametric linkage analysis. FBLN2 was identified as a candidate gene via analysis of WES data across the significant linkage region. A fbln2 knockout zebrafish line was established by CRISPR/Cas9 to examine the gene's role in craniofacial cartilage development. fbln2 was expressed specifically in the mandible during the zebrafish early development, while fbln2 knockout zebrafish exhibited craniofacial malformations with abnormal chondrocyte morphologies. Functional studies revealed that fbln2 knockout caused abnormal chondrogenic differentiation, apoptosis, and proliferation of cranial neural crest cells (CNCCs), and downregulated the bone morphogenic protein (BMP) signaling pathway in the zebrafish model. This study demonstrates the role of FBLN2 in CNCC development and BMP pathway regulation, and highlights FBLN2 as a candidate gene for Goldenhar syndrome, which may have implications for the selection of potential screening targets and the development of treatments for conditions like microtia-atresia.

Novel Loci (EIF4A2, ADIPOQ, TPRG1) for Triglyceride / High-density Lipoprotein Cholesterol Ratio Longitudinal Change (ΔTHR) among Subjects without Type 2 Diabetes: Evidence from the Long Life Family Study (LLFS) and the Framingham Heart Study (FHS) Offspring Cohort (OS).

Triglyceride (TG) /High density lipoprotein cholesterol (HDL-C) ratio (THR) represents a single surrogate predictor of hyperinsulinemia or insulin resistance that is associated with premature aging processes, risk of diabetes and increased mortality. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among subjects of European ancestry who had complete data from two exams collected about seven years apart from the Long Life Family Study (LLFS, n=1384), a study with familial clustering of exceptional longevity in the US and Denmark. Subjects with diabetes or using medications for dyslipidemia were excluded from this analysis. ΔTHR was derived using growth curve modeling, and adjusted for age, sex, field centers, and principal components (PCs). GWAS was conducted using a linear mixed model accounted for familial relatedness. Our linkage scan was built on haplotype-based IBD estimation with 0.5 cM average spacing. Heritability of ΔTHR was moderate (46%). Our GWAS identified a significant locus at the LPL (p=1.58e-9) for ΔTHR; this gene locus has been reported before influencing baseline THR levels. Our GWLS found evidence for a significant linkage with a logarithm of the odds (LODs) exceeding 3 on 3q28 (LODs=4.1). Using a subset of 25 linkage enriched families (pedigree-specific LODs>0.1), we assessed sequence elements under 3q28 and identified two novel variants (EIF4A2/ADIPOQ-rs114108468, p=5e-6, MAF=1.8%; TPRG1-rs16864075, p=3e-6, MAF=8%; accounted for ~28% and ~29% of the linkage, respectively, and 57% jointly). While the former variant was associated with EIF4A2 (p=7e-5) / ADIPOQ (p=3.49e-2) RNA transcriptional levels, the latter variant was not associated with TPRG1 (p=0.23) RNA transcriptional levels. Replication in FHS OS observed modest effect of these loci on ΔTHR. Of 188 metabolites from 13 compound classes assayed in LLFS, we observed multiple metabolites (e.g., DG.38.5, PE.36.4, TG.58.3) that were significantly associated with the variants (p<3e-4). our linkage-guided sequence analysis approach permitted our discovery of two novel gene variants EIF4A2/ADIPOQ-rs114108468 and TPRG1-rs16864075 on 3q28 for ΔTHR among subjects without diabetes selected for exceptional survival and healthy aging.

Integrating the ESM usage and work engagement for employee agility performance: based on regulatory focus theory

This present research aims to clarify the intricate conjunction of enterprise social media (ESM) utilization and employee agility with a main focus on uncovering the underlying mechanisms that work through the mediating influence of work engagement and the moderating influence of regulatory focus. Drawing upon regularity focus theory, 353 Chinese samples of ESM users in organizational contexts are analyzed using SPSS 23.0. The empirical findings substantiate a robust and significant positive linkage between ESM usage and worker agility. Further reinforcing the model, the mediating role of work engagement is established as it channels the impact of ESM usage on worker agility. Turning to the moderating effects, the study unveils the differential impact of prevention focus and promotion focus, wherein individuals with a lower prevention focus exhibit a more pronounced positive linkage between ESM usage and worker agility. Similarly, individuals with a higher promotion focus demonstrate a heightened positive association between ESM usage and worker agility. By comprehensively inspecting the intricate dynamics of ESM usage, work engagement, and regulatory focus, this study enhances our theoretical understanding of how these factors synergistically shape employee agility, ultimately furnishing organizations with invaluable insights to foster and cultivate an agile workforce.

Genome-wide linkage and association of novel genes and pathways with type 2 diabetes in Italian families

BackgroundType 2 diabetes mellitus (T2D) stands as one of the most prevalent chronic diseases globally, posing substantial health and economic burdens on society. Within the spectrum of T2D, familial cases emerge as a distinct entity characterized by a strong familial clustering of the disease. This phenomenon has long suggested that genetics contributes substantially to T2D susceptibility, motivating extensive research into the genetic determinants of familial T2D. MethodsWe recruited 212 multigenerational Italian families with multiple cases of T2D. The families were genotyped using genomic array (≥ 600k) derived from the UK Biobank Axiom Array platform. Informative markers were tested via Pseudomarker for linkage to and linkage disequilibrium (i.e., linkage joint to association) with T2D across the following models: dominant with complete penetrance (D1), dominant with incomplete penetrance (D2), recessive with complete penetrance (R1), and recessive with incomplete penetrance (R2). ResultsWe identified a total of 566 variants reaching genome-wide significant (P < 0.00005) linkage and/or association to/with the risk of T2D in Italian families. Of the 355 genes identified in our study, 341 (96%) are novel and have not been reported with T2D or any of its related phenotypes (i.e., obesity, metabolic syndrome, insulin resistance, polycystic ovary syndrome, and hyperglycemia). ConclusionOur study constitutes the first familial T2D-linkage and association study in the Italian population. However, the functional relevance of the novel variants and genes reported in our study remains to be explored.

Whole Genome Linkage and Association Analyses Identify DLG Associated Protein-1 as a Novel Positional and Biological Candidate Gene for Muscle Strength: The Long Life Family Study.

Grip strength is a robust indicator of overall health, is moderately heritable, and predicts longevity in older adults. Using genome-wide linkage analysis, we identified a novel locus on chromosome 18p (mega-basepair region: 3.4-4.0) linked to grip strength in 3755 individuals from 582 families aged 64 ± 12 years (range 30-110 years; 55% women). There were 26 families that contributed to the linkage peak (cumulative logarithm of the odds [LOD] score = 10.94), with 6 families (119 individuals) accounting for most of the linkage signal (LOD = 6.4). In these 6 families, using whole genome sequencing data, we performed association analyses between the 7312 single nucleotide (SNVs) and insertion deletion (INDELs) variants in the linkage region and grip strength. Models were adjusted for age, age2, sex, height, field center, and population substructure. We found significant associations between genetic variants (8 SNVs and 4 INDELs, p < 5×10-5) in the Disks Large-associated Protein 1 (DLGAP1) gene and grip strength. Haplotypes constructed using these variants explained up to 98.1% of the LOD score. Finally, RNAseq data showed that these variants were significantly associated with the expression of nearby Myosin Light Chain 12A (MYL12A), Structural Maintenance of Chromosomes Flexible Hinge Domain Containing 1 (SMCHD1), Erythrocyte Membrane Protein Band 4.1 Like 3 (EPB41L3) genes (p < .0004). The DLGAP1 gene plays an important role in the postsynaptic density of neurons; thus, it is both a novel positional and biological candidate gene for follow-up studies aimed at uncovering genetic determinants of muscle strength.

Thermochemical conversion of oil palm biomass and its applications: A bibliometric exploration of global trends over two decades

In the context of rising global palm oil production and increasing focus on renewable energy, this bibliometric analysis explores literature trends and the impact of scholarly articles on the thermochemical conversion of oil palm biomass (OPB). Data from 2004 to 2023, sourced from Scopus, was validated and analyzed using Microsoft Excel and VOSViewer. The search yielded 2215 articles after multiple phases of collecting and refining textual content from Scopus. The analysis maps out research frontiers, themes, and connections, including combustion, gasification, pyrolysis, torrefaction, and liquefaction. Malaysia emerged as the leading country in terms of research output. In terms of technologies, pyrolysis was the most researched technology. The analysis was further deepened to include specific application-related subtopics, focusing on keywords such as diesel, biofuel, adsorption, supercapacitor, phenol, and hydrogen production, which show significant linkage and occurrence in author keyword searches. This study provides a comprehensive overview of the research landscape in this field, highlighting crucial areas for future exploration.

The effect of software registration on manufacturing export

ABSTRACT Considering the pivotal role of the software industry in the digital economy, this article investigates the effect of software registration on China’s manufacturing exports from 2000 to 2013 against the backdrop of rapid growth in the digital economy and international trade. Our results indicate a positive association between software registration, a unique proxy for digital economy development, and manufacturing firm exports. This finding remains robust across various tests, including Bartik IV estimation, different estimators, and subsample analyses. Mechanism analysis suggests that software registration may bolster exports by reducing firms’ production and operational costs while mitigating information frictions in international markets, thereby incentivizing firms to expand their export activities to diverse markets. Furthermore, extended analyses reveal heterogeneous impacts across firm ownership, regions, industries, and destinations. Overall, our findings underscore the significant linkage between software registration and firm exports, providing a novel perspective on the digital economy’s influence on international trade.

Relationship of ESG Scores with Firm Performance: A Study of Indian Listed Companies

This study seeks to explore whether there is a substantial correlation between corporations’ ESG (Environmental, Social and Governance) ratings and their profitability, specifically return on assets (ROA). It aims to determine whether this correlation is positive, negative or neutral in nature. The research methodology involved an investigation of companies listed on the BSE500 stock index, analysing their ESG ratings for the years 2020 and 2021. The final dataset encompassed 148 companies, resulting in 296 observations for the two years, sourced from the Ace equity database. Panel regression analysis was employed to assess the link between ESG ratings (the independent variable) and ROA (the dependent variable), while also considering financial leverage and firm size as control factors. The results revealed a statistically significant negative linkage between ESG ratings and firm performance, as indicated by ROA, at a 5% significance level. The negative relation between ESG scores and firm performance (ROA) could be attributed to several factors. Organisations that prefer ESG initiatives often incur additional costs in areas like environmental compliance and employee welfare, which can temporarily reduce profitability. Moreover, ESG-conscious firms may make long-term investments that take time to generate returns, impacting short-term ROA. Additionally, stringent ESG standards may deter certain investors or customers, affecting revenue. However, over the long run, robust ESG practices can enhance sustainability and resilience, potentially leading to improved performance and risk mitigation.

Unlocking the path to environmental sustainability: navigating economic policy uncertainty, ICT, and environmental taxes for a sustainable future.

The study aims to gauge the impact of economic policy uncertainty, ICT, and environmental tax on environmental sustainability, which is measured by carbon emission and ecological footprint in a panel of 22 nations from 1997 to 2021. The present study has implemented the advanced panel data estimation techniques, including continuously updated fully modified (CUP-FM) and continuously updated bias-corrected (CUP-BC), dynamic seemingly unrelated regressions (DSUR), and nonlinear autoregressive distributed lagged (NARDL) in documenting the elasticities of target variables. Moreover, the directional causality has been tested through the D-H causality test. Study findings documented a positive and statistically significant linkage between EPU and environmental degradation. That is, EPU amplifies the emission of CO2 and ecological instability. The effects of ET and ICT are positively associated with environmental sustainability; that is, ET and ICT control the emission of CO2 and bring ecological improvement. This study contributes to the existing body of literature by conducting a thorough analysis of the relationship between various factors and their impact on environmental degradation. The study emphasizes the significance of every factor in influencing environmental outcomes. It provides policy suggestions to reduce CO2 emissions and promote ecological sustainability. The findings add valuable insights to the ongoing conversation about how to tackle environmental challenges in our constantly evolving world.

Genetic Diversity, Linkage Disequilibrium, and Population Structure in a Common Bean Reference Collection

An in-depth understanding of the extent and pattern of genetic diversity and population structure in crop populations is of paramount importance for any crop improvement program to efficiently promote the translation of genetic diversity into genetic gain. A reference collection of 150 common bean genotypes selected from the International Center for Tropical Agriculture’s global core collection was evaluated using single-nucleotide polymorphism (SNP) markers to quantify the amount of genetic diversity, linkage disequilibrium, and population structure. The cultivars and landraces of the collection were diverse and originated from 14 countries, and wild accessions were used as controls for each gene pool. The collection was genotyped using an SNP array, generating a total of 5398 locus calls distributed across the entire bean genome. The SNP data quality was checked, and two datasets were generated. The first dataset (Dataset_1) comprised a set of 5108 SNPs and 150 genotypes after filtering for 10% missing alleles and an MAF &lt; 0.05. The second dataset (Dataset_2) comprised a set of 2300 SNPs that remained after removing any null-allele SNPs and LD pruning for a criterion of r2 &lt; 0.2. Dataset_1 was used for a principal coordinate analysis (PCoA), phylogenetic relationship determination, an analysis of molecular variance (AMOVA), and a discriminant analysis of principal components. Dataset_2 was used for a population structure analysis using STRUCTURE software and is proposed for a genome-wide association study (GWAS). The population structure analysis split the reference collection into two subpopulations according to an Andean or Mesoamerican gene pool. The Mesoamerican populations displayed higher genetic differentiation and tended to split into more groups that were somewhat aligned with common bean races. Andean beans were characterized by a larger average LD but lower LD percentage, a small average genetic distance between members of the population, and a higher major allele frequency, which suggested narrower genetic diversity compared to the Mesoamerican gene pool. In conclusion, the results indicated the presence of high genetic diversity, which is useful for a GWAS. However, the presence of significant linkage disequilibrium requires that genetic distance be considered as a co-factor for any further genetic studies. Overall, the molecular variation observed in the genotypes shows that this reference collection is valuable as a genebank-derived diversity panel which is useful for marker trait association studies.

Abstract 137: Identification Of A Noncoding Genetic Variant In The Tissue Factor Locus That Reverses Lethal Thrombosis In Mice

Background: Thrombosis is initiated by tissue factor (TF, gene name F3 ) binding to coagulationFVII, with tissue factor pathway inhibitor (TFPI) inhibiting this complex. Alterations in TF orTFPI expression significantly affect thrombosis. Reducing TFPI expression by 50% ( Tfpi +/-) inmice results in a perinatal lethal phenotype on the Factor V Leiden homozygous( F5 L/L )prothrombotic background. We used the F5 L/L Tfpi +/- lethal phenotype to conduct a dominantsensitized whole genome ENU mutagenesis screen to suppress the F5 L/L Tfpi +/- lethality. Weidentified a Modifier of Factor 5 Leiden 6 (MF5L6) line with 72% penetrance and 85 F5 L/L Tfpi +/- offspring. A significant linkage peak (LOD=4.35),explaining half the suppressing effect andcontaining F3 (Chromosome 3) was identified. Goals/Hypothesis: To identify the genomic variant controlling F3 expression in the MF5L6 line. Methods: To quantify F3 expression in the surviving mice from MF5L6, quantitative PCR onliver, lung, and heart tissues from MF5L6 was performed. We used Sanger DNA and highthroughput sequencing to identify candidate TF regulatory variants in the F3 locus. Theprothrombin time assay was used to test the effects of reduced TF expression on in vitro bloodcoagulation. Results: Two distinct expression profiles in the lung and liver of the MF5L6 mice wereobserved, those that had a 50% reduction in F3 mRNA and those that did not. Heart tissuesexhibited one expression profile, suggesting that the variant regulates F3 expressiontissue-specifically. Sanger sequencing of the F3 coding region revealed no coding mutations inMF5L6 mice. Whole genome sequencing identified two novel candidate variants (in unknownF3 regulatory elements) in the 200 kilobase upstream region of F3 . The 50% reduction in F3 resulted in significant changes in coagulation by the prothrombin assay (n=18,p&lt;0.0009). Conclusion: We identified novel candidate variants for regulating F3 gene expression and aredetermining their mechanism of action. Investigation of these variants will provide new insightsinto the regulation of F3 and enable us to identify the variant(s) responsible for the remainder ofthe thrombosis suppressing effect in MF5L6. Our findings provide new insights into the geneticregulation of thrombosis.

Building aspiring teachers' capabilities, professional and skill development: Auspice to quality teaching practice in technical vocational education and training institutions

AbstractThere is an increasing need to train and retrain personnel that would be saddled with the capabilities, professional and skill developmental requirement that meets societal needs. In this case, there is need for adequately trained personnel that will bridge the gap between societal needs; industrial needs with classroom instructions and vice versa. Therefore, this study examines the influence of building aspiring teachers' capabilities, professional and skill development as an auspice to quality teaching activities in technical vocational education and training institutions. Samples were selected using a multistage sampling technique. The collected data from 945 aspiring teachers was analysed using empirical analysis with AMOS SPSS v.23. Hayes PROCESS macro was used for mediation analyses. The result of the study indicated that self‐efficacy and professional skills with knowledge of instructional delivery and personal capabilities have strong significant linkage. There is also a mediating interaction of attention to relationship on the relationship between constructive teaching and personal capabilities. TVET institutions should ensure continuous professional development by concentrating on the requirements concerning teaching and learning, individual resources and social support for coping with various requirements.