Search

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease, making it a leading cause of death worldwide. Several genome-wide association studies (GWAS) have been conducted to identify loci associated with COPD. However, different ancestral genetic compositions for the same disease across various populations present challenges in studies involving multi-population data. In this study, we aimed to identify protein-coding genes associated with COPD by prioritizing genes for each population's GWAS data, and then combining these results instead of performing a common meta-GWAS due to significant sample differences in different population cohorts. Lung function measurements are often used as indicators for COPD risk prediction; therefore, we used lung function GWAS data from two populations, Japanese and European, and re-evaluated them using a multi-population gene prioritization approach. This study identified significant single nucleotide variants (SNPs) in both Japanese and European populations. The Japanese GWAS revealed nine significant SNPs and four lead SNPs in three genomic risk loci. In comparison, the European population showed five lead SNPs and 17 independent significant SNPs in 21 genomic risk loci. A comparative analysis of the results found 28 similar genes in the prioritized gene lists of both populations. We also performed a standard meta-analysis for comparison and identified 18 common genes in both populations. Our approach demonstrated that trans-ethnic linkage disequilibrium (LD) could detect some significant novel associations and genes that have yet to be reported or were missed in previous analyses. The study suggests that a gene prioritization approach for multi-population analysis using GWAS data may be a feasible method to identify new associations in data with genetic diversity across different populations. It also highlights the possibility of identifying generalized and population-specific treatment and diagnostic options. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the potential causal link between mitochondrial function and breast cancer using the Mendelian randomization (MR) analysis. Methods: The data used for this study were obtained from genomewide association studies (GWAS) databases on mitochondrial biological function and breast cancer. Mitochondrial function was considered the exposure variable, breast cancer the outcome variable, and specific single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs). Two MR methods, inverse variance weighting (IVW) and MR‐Egger regression, were used to assess the causal association between mitochondrial function and breast cancer. Data analysis and visualization were performed using R software. Results: The results of the analysis revealed that several genes, including 39S ribosomal protein L34, pyruvate carboxylase, rRNA methyltransferase 3, and cytochrome c oxidase assembly factor 3 homolog, are causally linked to an increased risk of breast cancer in European populations. In addition, cytochrome c oxidase subunit 8A and ADP‐ribose pyrophosphatase were found to be protective factors against breast cancer in European populations. In East Asian populations, 39S ribosomal protein L52, ATP synthase subunit beta, and pyruvate dehydrogenase (acetyl‐transferring) were identified as causal risk factors for breast cancer. Conversely, 39S ribosomal protein L32, ADP‐ribose pyrophosphatase, and cytochrome c oxidase subunit 8A were identified as protective factors against breast cancer in this population. Conclusion: In conclusion, this study provides evidence of a causal relationship between mitochondrial function and breast cancer in both European and East Asian populations. Additional research is warranted to further elucidate the mechanisms underlying this association. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods and Results Conclusion The mitochondrial contact site and cristae organising system (MICOS) complex is required for cristae formation and is composed of seven proteins. Among the genes of MICOS complex, variants of MICOS13, IMMT and APOO have been reported to cause diseases.We report a case in which whole genome sequencing identified a variant of the MICOS10 gene associated with mitochondrial hepatopathy along with mitochondrial DNA depletion. We identified the deletion g.19596826_19601303del and the single nucleotide variant c.173G>C (p.Cys58Ser). The deletion including exon 1 might have caused complete loss of gene expression, indicating monoallelic expression from RNA sequencing. MIC10 was lost at the protein level in the patient's fibroblasts, and mitochondrial oxygen consumption was impaired. These were restored by overexpression of MICOS10 in the patient's fibroblasts.Taken together, these findings indicate that MICOS10 is a causative gene for hepatopathy and neuropathy, a disease very similar to that associated with MICOS13. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly often accompanied by other structural anomalies and/or neurobehavioral manifestations. Rare de novo protein-coding variants and copy-number variations contribute to CDH in the population. However, most individuals with CDH remain genetically undiagnosed. Here, we perform integrated de novo and common-variant analyses using 1,469 CDH individuals, including 1,064 child-parent trios and 6,133 ancestry-matched, unaffected controls for the genome-wide association study. We identify candidate CDH variants in 15 genes, including eight novel genes, through deleterious de novo variants. We further identify two genomic loci contributing to CDH risk through common variants with similar effect sizes among Europeans and Latinx. Both loci are in putative transcriptional regulatory regions of developmental patterning genes. Estimated heritability in common variants is ∼19%. Strikingly, there is no significant difference in estimated polygenic risk scores between isolated and complex CDH or between individuals harboring deleterious de novo variants and individuals without these variants. The data support a polygenic model as part of the CDH genetic architecture. Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly. Genetic diagnoses are made in ∼30% of people with CDH, but the rest of the cases remain unexplained. We identified rare variants in novel genes and common variants in two loci that support a polygenic model for CDH genetic architecture. [ABSTRACT FROM AUTHOR]

Despite the breeding efforts by many institutions, maize (Zea mays L.) productivity in sub‐Saharan Africa is still low. A limited number of productive maize hybrids have been developed partly due to a lack of knowledge on the diversity and heterotic relationship of the germplasm, especially in public breeding programs. Understanding the extent of diversity, structure, and heterotic grouping of available maize germplasm originating from different breeding programs is important to enhance long‐term genetic gain in hybrid maize breeding programs by optimizing heterotic pools using modern breeding tools. Information about the genetic structure of the available germplasm could help breeders design effective breeding strategies to improve yield. This study was conducted to determine the genetic diversity, population structure, and heterotic alignment among 187 elite maize inbred lines from the IITA (International Institute of Tropical Agriculture) and CIMMYT (International Maize and Wheat Improvement Center) maize breeding programs. The inbred lines were genotyped with 9857 Diversity Array Technology sequencing based single nucleotide polymorphism markers. Hierarchical clustering revealed three major groups, with some subgroups consistent with the selection history, and pedigree of the inbred lines. Three broad groups were detected: two consisting of CIMMYT lines and a mixed group consisting of both CIMMYT and IITA inbred lines. The STRUCTURE analysis revealed six subpopulations (fixation index value = 0.58), which depicts a moderate genetic diversity among the materials. Population 2 comprises the highest number of genotypes (102) from both programs. More than 89% of the elite lines had homozygosity exceeding 95%, with the remaining lines requiring further inbreeding through repeated self‐pollination. There was inconsistency in the predetermined heterotic groups' alignment between CIMMYT and IITA elite inbred lines. Analysis of molecular variance revealed that 96% of the total variation was accounted for by differences within groups, with the remaining 4% representing the variation between groups. This suggests that the two programs can benefit from germplasm exchange for the improvement of maize productivity. [ABSTRACT FROM AUTHOR]

The article discusses the relevance of the E756del common variant in the PIEZO1 gene for haemolytic anaemia and hepatic iron overload, particularly in patients with dehydrated hereditary stomatocytosis (DHS). The variant is prevalent in the African-descent population and has been associated with increased red blood cell dehydration, mild anaemia, alterations in iron balance, and protection against malaria. The study analyzed a cohort of patients with hereditary erythrocyte and iron metabolism defects, highlighting the impact of the E756del variant on clinical parameters and iron metabolism. The findings suggest that the E756del variant functions as a polymorphism with mild to moderate effects on haemolytic anaemia and hepatic iron overload, emphasizing the importance of monitoring iron balance in affected individuals. [Extracted from the article]

Background: A single nucleotide polymorphism (SNP) is a variation in the DNA sequence that results from the alteration of a single nucleotide in the genome. Atorvastatin is used to treat hypercholesterolemia. It belongs to a class of drugs called statins, which lower elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Research findings on the associations between the response to atorvastatin and genetic polymorphisms in CYP3A4 and CYP3A5 are inconclusive. The effects of CYP3A4*1B (rs2740574 C/T) and CYP3A5*3 (rs776746 T/C) on atorvastatin therapy have not been previously studied among Egyptians. Objective: This research aimed to investigate the effects of the genetic polymorphisms CYP3A4*1B and CYP3A5*3 on atorvastatin treatment in Egyptians. Methods: In this prospective cohort study, 100 subjects were genotyped for these SNPs. All participants were screened for serum lipid profiles, liver enzymes, total bilirubin (TB), and creatine kinase (CK) before and after 40 mg postatorvastatin therapy. Atorvastatin plasma levels were assessed posttreatment; atorvastatin pharmacokinetics were evaluated in five carriers of the CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes. Results: The allele frequencies of the CYP3A4*1B and CYP3A5*3 SNPs were 86% and 83%, respectively. The CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes significantly improved the serum triglyceride (TG) level (P < 0.05) and elevated the TB level (P < 0.001). Atorvastatin plasma levels were greater in CYP3A4*1B (T/T) (P < 0.05) and CYP3A5*3 (C/C) (P < 0.001) genotype carriers. Both SNPs significantly affected the pharmacokinetics of atorvastatin compared with those of Egyptian volunteers and various ethnic populations. Conclusions: The CYP3A4*1B and CYP3A5*3 variants were prevalent in the study participants and could impact the effectiveness and safety of atorvastatin therapy. The mutant genotype of the CYP3A4*1B SNP and the CYP3A5*3 SNP led to high atorvastatin levels. Both variants had a notable effect on the pharmacokinetics of atorvastatin among Egyptians compared with healthy Egyptians and volunteers from other ethnic populations. Overall, clinicians can learn more about the impact of both variants in response to atorvastatin. [ABSTRACT FROM AUTHOR]

Background: In previous observational studies and meta-analyses, childhood attention deficit hyperactivity disorder (ADHD) is found to have a significant association with screen time. However, the causal associations between them remain unclear. Method: This study performed a bidirectional two-sample Mendelian randomization (MR) analysis to confirm the causality between screen time and childhood ADHD. Large-scale genome-wide association studies (GWAS) datasets derived from the Psychiatric Genomics Consortium (PGC) and the UK Biobank were used to identify single nucleotide polymorphisms (SNPs) associated with exposure and outcome. Four categories of datasets were selected to represent screen time. The SNPs that are significantly associated with exposure data (P < 5e-08) and have a strong correlation with the exposure in the F-statistic (F > 10) were selected as instrumental variables. This study also used the PhenoScanner V2 database and the LDlink webtool to exclude confounding factors, and the MR-PRESSO method (p < 0.05) was employed to eliminate outliers with bias. Five commonly used methods were employed to assess the interaction and the Inverse Variance Weighted (IVW) method was utilized as the primary basis for determining the MR estimates in this study. Results: The MR analysis revealed that the length of mobile phone use (OR, 1.848; 95% CI, 1.3360-2.5558; p=2.07e-4) and the time spent watching television (OR, 2.104; 95% CI, 1.3958-3.1703; p=3.8e-4) increased the risk of childhood ADHD. Although the causal relationships were exclusively identified through the IVW and weighted median methods, the results retained their statistical significance following correction. In the reverse analysis, no evidence was found to support an effect of childhood ADHD on screen time. The sensitivity analysis conducted on the significant findings revealed no evidence of horizontal pleiotropy or heterogeneity. Conclusion: This study provides some evidence for the causality of screen time and childhood ADHD. Given the limitations of our study, further research is required to comprehensively investigate this relationship. [ABSTRACT FROM AUTHOR]

Shade has a direct impact on photosynthesis and production of plants. Exposure to shade significantly reduces crops yields. Identifying shade-tolerant genomic loci and soybean varieties is crucial for improving soybean yields. In this study, we applied a shade treatment (30% light reduction) to a natural soybean population consisting of 264 accessions, and measured several traits, including the first pod height, plant height, pod number per plant, grain weight per plant, branch number, and main stem node number. Additionally, we performed GWAS on these six traits with and without shade treatment, as well as on the shade tolerance coefficients (STCs) of the six traits. As a result, we identified five shade-tolerance varieties, 733 SNPs and four candidate genes over two years. Furthermore, we developed four kompetitive allele-specific PCR (KASP) makers for the STC of S18_1766721, S09_48870909, S19_49517336, S18_3429732. This study provides valuable genetic resources for breeding soybean shade tolerance and offers new insights into the theoretical research on soybean shade tolerance. [ABSTRACT FROM AUTHOR]

Northern corn leaf blight (NCLB), caused by Setosphaeria turcica , is a major fungal disease affecting maize production in sub-Saharan Africa. Utilizing host plant resistance to mitigate yield losses associated with NCLB can serve as a cost-effective strategy. In this study, we conducted a high-resolution genome-wide association study (GWAS) in an association mapping panel and linkage mapping with three doubled haploid (DH) and three F3 populations of tropical maize. These populations were phenotyped for NCLB resistance across six hotspot environments in Kenya. Across environments and genotypes, NCLB scores ranged from 2.12 to 5.17 (on a scale of 1–9). NCLB disease severity scores exhibited significant genotypic variance and moderate-to-high heritability. From the six biparental populations, 23 quantitative trait loci (QTLs) were identified, each explaining between 2.7% and 15.8% of the observed phenotypic variance. Collectively, the detected QTLs explained 34.28%, 51.37%, 41.12%, 12.46%, 12.11%, and 14.66% of the total phenotypic variance in DH populations 1, 2, and 3 and F3 populations 4, 5, and 6, respectively. GWAS, using 337,110 high-quality single nucleotide polymorphisms (SNPs), identified 15 marker–trait associations and several putative candidate genes linked to NCLB resistance in maize. Joint linkage association mapping (JLAM) identified 37 QTLs for NCLB resistance. Using linkage mapping, JLAM, and GWAS, several QTLs were identified within the genomic region spanning 4 to 15 Mbp on chromosome 2. This genomic region represents a promising target for enhancing NCLB resistance via marker-assisted breeding. Genome-wide predictions revealed moderate correlations with mean values of 0.45, 0.44, 0.55, and 0.42 for within GWAS panel, DH pop1, DH pop2, and DH pop3, respectively. Prediction by incorporating marker-by-environment interactions did not show much improvement. Overall, our findings indicate that NCLB resistance is quantitative in nature and is controlled by few major-effect and many minor-effect QTLs. We conclude that genomic regions consistently detected across mapping approaches and populations should be prioritized for improving NCLB resistance, while genome-wide prediction results can help incorporate both major- and minor-effect genes. This study contributes to a deeper understanding of the genetic and molecular mechanisms driving maize resistance to NCLB. [ABSTRACT FROM AUTHOR]

Lentil (Lens culinaris Medikus) is a nutrient-rich, cool-season food legume that is high in protein, prebiotic carbohydrates, vitamins, and minerals. It is a staple food in many parts of the world, but crop performance is threatened by climate change, where increased temperatures and less predictable precipitation can reduce yield and nutritional quality. One mechanism that many plant species use to mitigate heat and drought stress is the production of disaccharides, oligosaccharides and sugar alcohols, collectively referred to as low molecular weight carbohydrates (LMWCs). Recent evidence indicates that lentil may also employ this mechanism – especially raffinose family oligosaccharides and sugar alcohols – and that these may be suitable targets for genomic-assisted breeding to improve crop tolerance to heat and drought stress. While the genes responsible for LMWC biosynthesis in lentil have not been fully elucidated, single nucleotide polymorphisms and putative genes underlying biosynthesis of LMWCs have been identified. Yet, more work is needed to confirm gene identity, function, and response to abiotic stress. This review i) summarizes the diverse evidence for how LMWCs are utilized to improve abiotic stress tolerance, ii) highlights current knowledge of genes that control LMWC biosynthesis in lentil, and iii) explores how LMWCs can be targeted using diverse genomic resources and markers to accelerate lentil breeding efforts for improved stress tolerance. [ABSTRACT FROM AUTHOR]

Objective: The relationship between gut microbiome and trimethylamine oxide (TMAO) has not been fully elucidated. We aimed to assess the causal effects of different gut microbes on TMAO using Mendelian randomization (MR). Methods: Gut microbiome and TMAO datasets were acquired from genome-wide association studies and screened for single nucleotide polymorphisms according to the basic assumptions of MR. Inverse variance weighted was used as the main method in MR analysis to assess the causal relationship between the gut microbiome and TMAO. Finally, the MR-Egger intercept, Cochran's Q test, and leave-one-out sensitivity analysis were used to assess the horizontal pleiotropy, heterogeneity, and robustness of the results, respectively. Results: MR analysis revealed that the species Bacteroides finegoldii (odds ratio [OR] 1.064, 95% confidence interval [CI] 1.003 to 1.128, p = 0.039), family Sutterellaceae (OR 1.188, 95% CI 1.003 to 1.407, p = 0.047), and phylum Pseudomonadota (OR 1.205, 95% CI 1.036 to 1.401, p = 0.016), as well as the species Bacteroides uniformis (OR 1.263, 95% CI 1.039 to 1.535, p = 0.019), were positively associated with increased genetic susceptibility to TMAO. In contrast, the species Bacteroides thetaiotaomicron (OR 0.813, 95% CI 0.696 to 0.950, p = 0.009) and Bilophila wadsworthia (OR 0.828, 95% CI 0.690 to 0.995, p = 0.044) were associated with reduced genetic susceptibility to TMAO. Additionally, the MR-Egger intercept indicated no horizontal pleiotropy (p ≥ 0.05), and Cochran's Q test and sensitivity analysis demonstrated that the results were not heterogeneous (p ≥ 0.05) and were robust. Conclusion: Our findings revealed the role of the phylum Pseudomonadota, family Sutterellaceae, species Bacteroides finegoldii , and Bacteroides uniformis in increasing TMAO, as well as the species Bacteroides thetaiotaomicron and Bilophila wadsworthia in decreasing TMAO. This study provides new insights into the relationship between the gut microbiome and TMAO levels. [ABSTRACT FROM AUTHOR]

The study presents a comprehensive investigation into the genetic determinants of 100-day milk yield (100DMY), 305-day milk yield (305DMY), total milk yield (TMY), and persistency using first lactation records of 374 Holstein heifers reared in a private farm at Çanakkale province of Türkiye, employing a genome-wide association study (GWAS) approach. The research underscores the substantial genetic component underlying these economically important traits through detailed descriptive statistics and heritability estimations. The estimated moderate to high heritabilities (0.32–0.54) for milk production traits suggest the feasibility of targeted genetic improvement strategies. By leveraging GWAS, the study identifies many significant and suggestively significant single nucleotide polymorphisms (SNP) associated with studied traits. Noteworthy genes have identified in this analysis include BCAS3, MALRD1, CTNND2, DOCK1, TMEM132C, NRP1, CNTNAP2, GPRIN2, PLEKHA5, GLRA1, SCN7A, HHEX, KTM2C, RAB40C, RAB11FIP3, and FXYD6. These findings provide valuable understandings of the genetic background of milk production and persistency in Holstein cattle, shedding light on specific genomic regions and candidate genes playing pivotal roles in these traits. This research contributes valuable knowledge to the field of dairy cattle genetics and informs future breeding efforts to improve milk production sustainability and efficiency in Holstein cattle populations. [ABSTRACT FROM AUTHOR]

Background: Blood and urine biomarkers have been associated with urologic tumors, but their causal relationship with urologic tumors is unclear. Methods: We performed a bidirectional Mendelian randomization (MR) analysis of the association between 35 blood and urine biomarkers and urological tumors in our discovery cohort. A Bayesian weighting approach was used to validate the positive results identified in the discovery cohort, and steiger filtering analysis was used to distinguish causality from reverse causality. Bayesian colocalization analysis was used to analyze which single nucleotide polymorphisms (SNPs) specifically co-located between the positive blood and urine biomarkers and the disease phenotypes were driven, and MR-positive results from the discovery cohort and the validation cohort were combined using the MR-meta method. Results: Several blood and urine biomarkers were found to be significantly and causally associated with urologic cancers. Notably, calcium (OR: 1.34, 95%CI 1.10–1.63, P = 0.0040) and sex hormone-binding globulin (SHBG) (OR: 0.81, 95%CI 0.70–0.95, P = 0.0092) were associated with bladder cancer; gamma glutamyl transferase (GGT) (OR: 0.91, 95%CI 0.83–0.99, P = 0.0209), lipoprotein A (Lp(a)) (OR: 1.12, 95%CI 1.01–1.24, P = 0.0399), and insulinlike growth factor 1 (IGF 1) (OR: 1.10, 95%CI 1.01–1.20, P = 0.0220) were linked to prostate cancer (PCa); non albumin protein (OR: 0.78, 95%CI 0.65–0.93, P = 0.0065) and total protein (OR: 0.80, 95%CI 0.64–0.99, P = 0.0380) were linked to renal cancer; and apolipoprotein A (Apo-A) (OR: 0.56, 95%CI 0.32–0.98, P = 0.0426) and urate (OR:1.89, 95%CI 1.03–3.47, P = 0.0399) were associated with renal pelvis cancer. These associations were validated in an independent cohort, with GGT, IGF 1, and Lp(a) being consistently linked to PCa. Conclusion: This study identified significant biomarkers associated with urological cancers in blood and urine. These include GGT, IGF 1, and Lp(a), which are strong biomarkers for PCa. In addition, the findings of this study provide evidence for a handful of risk and protective factors for the development of urologic cancers. [ABSTRACT FROM AUTHOR]

Strict biennials are among the least known lifecycles in plant ecology due to their rarity in nature, and their population genetics still remain unknown. The present study addressed the strict biennial lifecycle and associated population genetics of Pedicularis hallaisanensis , an endangered endemic plant in Korea. All P. hallaisanensis individuals were counted in August from 2021 to 2023 in the wild population of Gayasan National Park, and lifecycle and morphological changes were monitored monthly. A de novo draft genome and single nucleotide polymorphism (SNP) analysis were used to study the population's genetic structure. P. hallaisanensis strictly requires a 2-year lifecycle per generation, including 8 and 10 months of growing periods as a first-year seedling and second-year adult, respectively. Facultative annual and perennial lifecycles were undetected, resulting in odd-year and even-year flowering cohorts. Permutational multivariate analysis of variance on the detected 3,716 SNPs demonstrated that the flowering group (p < 0.005), microhabitat (p < 0.001), and their interaction (p < 0.01) had a significant effect on genetic structure, which was differentiated between odd-year and even-year flowering cohorts. Other cluster analyses also showed that a microhabitat under historical anthropogenic interventions contained lowered genetic diversity due to a decreased genetic distance between odd-year and even-year flowering cohorts (p < 0.05). Overall, the findings suggest that excessive anthropogenic interventions should be avoided to preserve genetic diversity in the wild P. hallaisanensis population. Moreover, conservation programs for similar biennial plants should collect wild breeds from both odd-year and even-year flowering cohorts to improve the genetic diversity of artificially propagated individuals. [ABSTRACT FROM AUTHOR]

Introduction: Cutibacterium acnes can both be a helpful colonizer of the human skin as well as the causative agent of acne and purulent infections. Until today, it is a moot point whether there are C. acnes strains exclusively devoted to be part of the skin microbiome and others, that carry special features enabling them to cause disease. So far, the search for the molecular background of such diverse behavior has led to inconsistent results. Methods: In the present study, we prospectively collected C. acnes strains from 27 infected persons and 18 healthy controls employing rigid selection criteria to ensure their role as infectious agent or colonizer. The genome sequences from these strains were obtained and carefully controlled for quality. Results: Deduced traditional phylotyping assigned almost all superficial isolates to type IA1, while the clinical strains were evenly distributed between types IA1, IB, and II. Single locus sequence typing (SLST) showed a predominance of A1 type for the control strains, whereas 56% of the clinical isolates belonged to types A1, H1 and K8. Pangenome analysis from all the present strains and 30 published genomes indicated the presence of an open pangenome. Except for three isolates, the colonizing strains clustered in clades separate from the majority of clinical strains, while 4 clinical strains clustered with the control strains. Identical results were obtained by a single nucleotide polymorphism (SNP) analysis. However, there were no significant differences in virulence gene contents in both groups. Discussion: Genome-wide association studies (GWAS) from both the pangenome and SNP data consistently showed genomic differences between both groups located in metabolic pathway and DNA repair genes. Thus, the different behavior of colonizing and infectious C. acnes strains could be due to special metabolic capacities or flexibilities rather than specific virulence traits [ABSTRACT FROM AUTHOR]

Background: The telomere has long been regarded as a dependable biomarker for cellular senescence. The lung function can reflect the function and status of the lungs. As individuals age beyond adulthood, there is a gradual decline in lung function. However, the existence of a associated between leukocyte telomere length (LTL) and lung function remains uncertain. Methods: A two-sample Mendelian randomization (MR) analysis was used. The Single-nucleotide polymorphisms (SNPs) of LTL from the genome-wide association (GWAS) study were used as exposure instruments variable, and the lung function indicator including Forced expiratory volume in 1-s (FEV1), FEV1 Best measure, FEV1 predicted and Forced vital capacity (FVC) from the Neale Lab and MRC-IEU were used as outcomes. The associated between the exposures and outcomes was assessed using inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Sensitivity analysis was conducted using Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and Steriger test. Results: Using the IVW method, a significant association was identified between genetically determined telomere length extension and enhanced lung function in FEV1, with ukb-a-336 (P = 0.127, OR = 1.028,95CI% = 1.003–1.042) and ukb-b-19657 (P = 7.26E-05, OR = 1.051,95CI% = 1.025–1.077),in FEV1 predicted, ukb-a-234 (P = 0.013, OR = 1.029,95CI% = 1.003–1.042), ukb-b-8428 (P = 0.001, OR = 1.032,95CI% = 1.012–1.052), in FEV1 best measure, ukb-a-231 (P = 7.24E-05, OR = 1.050,95CI% = 1.025–1.075), ukb-b-11141 (P = 1.40E-09, OR = 1.067,95CI% = 1.045–1.090).The sensitivity analysis did not reveal heterogeneity or horizontal pleiotropy.Meanwhile, the Steriger test results also indicate that the directionality between exposure and outcome is correct. Therefore, the results indicated robustness. Conclusion: There is a correlation between longer LTL and better lung function in the European dataset. [ABSTRACT FROM AUTHOR]

Objective: This study aims to analyze the causal relationship between autoimmune thyroiditis (AIT) and inflammatory bowel disease (IBD) using bidirectional Mendelian randomization (MR). Methods: Single nucleotide polymorphisms were obtained from FinnGen. Exposure-outcome causality was assessed using inverse variance weighted, MR-Egger, and weighted median. MR-Egger intercept, Cochran's Q, and leave-one-out sensitivity analysis were used to evaluate horizontal pleiotropy, heterogeneity, and robustness, respectively. Results: Forward analysis revealed no significant association between AIT and the risk of ulcerative colitis (UC) (odds ratio [OR] 1.008, 95% confidence interval [CI] 0.986 to 1.03, p = 0.460) or Crohn's disease (CD) (OR 0.972, 95% CI 0.935 to 1.010, p = 0.143). Reverse analysis showed that UC (OR 0.961, 95% CI 0.783 to 1.180, p = 0.707) was not associated with AIT risk, while CD (OR 2.371, 95% CI 1.526 to 3.683, p < 0.001) was linked to an increased risk of AIT. Intercept analysis and Cochran's Q test indicated no horizontal pleiotropy or heterogeneity. Sensitivity analysis confirmed the robustness of the MR results. Conclusion: This MR analysis suggests that CD, but not UC, is a risk factor for AIT, whereas AIT is not associated with the risk of IBD. Proactive prevention and treatment of CD can help mitigate the risk of AIT. [ABSTRACT FROM AUTHOR]

Body conformation traits are directly associated with longevity, fertility, health, and workability in dairy cows and have been under direct genetic selection for many decades in various countries worldwide. The main objectives of this study were to perform genome-wide association studies and functional enrichment analyses for fourteen body conformation traits using imputed high-density single nucleotide polymorphism (SNP) genotypes. The traits analyzed include body condition score (BCS), body depth (BD), bone quality (BQ), chest width (CW), dairy capacity (DC), foot angle (FAN), front legs view (FLV), heel depth (HDe), height at front end (HFE), locomotion (LOC), rear legs rear view (RLRV), rear legs side view (RLSV), stature (ST), and a composite feet and legs score index (FL) of Holstein cows scored in Canada. De-regressed estimated breeding values from a dataset of 39,135 North American Holstein animals were used as pseudo-phenotypes in the genome-wide association analyses. A mixed linear model was used to estimate the SNP effects, which ranged from 239,533 to 242,747 markers depending on the trait analyzed. Genes and quantitative trait loci (QTL) located up to 100 Kb upstream or downstream of the significant SNPs previously cited in the Animal QTLdb were detected, and functional enrichment analyses were performed for the candidate genes identified for each trait. A total of 20, 60, 13, 17, 27, 8, 7, 19, 4, 10, 13, 15, 7, and 13 genome-wide statistically significant SNPs for Bonferroni correction based on independent chromosomal segments were identified for BCS, BD, BQ, CW, DC, FAN, FLV, HDe, HFE, LOC, RLRV, RLSV, ST, and FL, respectively. The significant SNPs were located across the whole genome, except on chromosomes BTA24, BTA27, and BTA29. Four markers (for BCS, BD, HDe, and RLRV) were statistically significant when considering a much stricter threshold for the Bonferroni correction for multiple tests. Moreover, the genomic regions identified overlap with various QTL previously reported for the trait groups of exterior, health, meat and carcass, milk, production, and reproduction. The functional enrichment analyses revealed 27 significant gene ontology terms. These enriched genomic regions harbor various candidate genes previously reported as linked to bone development, metabolism, as well as infectious and immunological diseases. [ABSTRACT FROM AUTHOR]

Background and aims: A number of case reports have documented the occurrence of acute hepatic and renal toxicity during treatment with deferasirox (DFX). The precise mechanisms underlying these adverse events remain unclear, with the time to toxicity varying considerably between patients—some experiencing it within weeks of treatment initiation, while others after several years. Recent studies have underscored the association of pharmacogenetic variants in genes responsible for the metabolism and clearance of DFX (ABCC2 , ABCG2 , and UGT1A1) in the development of toxicity. We present the case of an 8-year-old patient with beta thalassemia major who developed acute hepatic failure years after the initiation of DFX therapy. After ruling out the most likely causes, we performed a pharmacogenetic analysis, which suggested a possible link between the patient's genotype and the development of toxicity. Methods: Sanger sequencing was performed for the most extensively studied single nucleotide polymorphisms (SNPs) studied associated with changes in transporter/enzyme function: ABCC2 rs717620 (c.-24C>T), rs2273697 (c.1249G>A), rs8187710 (c.4544G>A), rs369192412 (g.99781071delG); ABCG2 rs2231142 (c.421C>A); UGT1A1 *6 rs4148323 (c.211G>A), *28 rs3064744 (g.233760235TA[8]), *36 rs3064744 (g.233760235TA[6]) and *37 rs3064744 (g.233760235TA[9]). Results: The patient is heterozygous for two ABCC2 variants, namely rs717620 (c.-24C>T) and rs2273697 (c.1249G>A). These variants have the potential to cause a reduction in transporter function, which could in turn result in decreased drug clearance and increased toxicity. Discussion: The precise mechanism by which toxicity developed in this case remains unclear and is likely multifactorial. However, it is probable that the presence of SNPs in the gene ABCC2 played a substantial role. Our findings align with those of previously published reports of remarkably similar cases, where patients also exhibited genetic variants in the gene ABCC2. [ABSTRACT FROM AUTHOR]

Introduction: In collaboration with the Minnesota Hmong community, we have previously discovered significant differences in allele frequencies for key Single Nucleotide Variations (SNVs) within Very Important Pharmacogenes (VIPs) between Hmong and East Asians. Recognizing the potential clinical implications of these observed differences, we sought to validate these observations in a Hmong cohort residing in California, the state with the largest Hmong population in the US. Robust validation of these differences would affect motivation for clinicians treating individuals who identify as Hmong to consider pharmacogenomic (PGx) testing as a means to improve clinical decision making when using therapeutic agents in this unique population. Method: Guided by California Hmong community leaders and utilizing the basic approach of community-based participatory research, demographic, clinical information and a buccal swab was obtained from Hmong adults residing in California. A commercial PGx testing panel was performed on these samples and specific allele frequencies of interest were compared between California and Minnesota Hmong. Allele frequency differences between California Hmong, East Asians and Europeans, were also compared. Return-of-PGx-results and presentations of group data were made to members of the Hmong along with PGx educational sessions to help interpret the observations. Results: In 118 California Hmong who completed the study, the allele frequencies for SNV's were similar to previous Minnesota Hmong results. Furthermore, out of the 18 SNVs that were not previously reported in Hmong, allele frequencies were statistically different in 38% (7/18) of SNVs comparing California Hmong to East Asians, and in 77.8% (14/18) SNVs comparing California Hmong to Europeans. Conclusion: These results validate the original study's findings that Hmong people living in different US locations have similar allele frequencies for key PGx genes. Further, for many of these PGx genes, their allele frequencies are significantly different compared to either East Asians or Europeans. Clinicians should consider these important differences when prescribing medications for people who identify as Hmong. [ABSTRACT FROM AUTHOR]

Introduction: L-Asparaginase (L-Asp) is a key drug in the treatment of acute lymphoblastic leukemia (ALL); however, it is commonly associated with the occurrence of adverse events (AE). Risk factors such as age, sex, nutritional status, and some single nucleotide variants (SNVs) in specific genes could be related to hypersensitivity reactions to L-Asp. The objective of this study was to identify the influence of individual characteristics and three SNVs in the GRIA1 and NFATC2 genes on the occurrence of the most significant adverse events caused by the use of L-Asp in Mexican children with ALL. Methods: Eighty-five children from ages 0–17 years old diagnosed with ALL were included. The patients were treated at two hospital centers in Mexico. The SNV genotypes of the GRI1A and NFATC2 genes studied were examined using real-time qPCR. The evaluation of AE was carried out according to the Common Terminology Criteria for adverse events, and the determination of anti-L-Asp antibodies was conducted using Western blot immunoassay. Results: Homozygosity (AA) of the GRIA1 rs4958351 SNV was significantly associated with the occurrence of AE with the use of L-Asp (OR = 4.05; 95% CI = 1.06 to 15.40, p = 0.04) and was strongly associated with the development of anti-L-Asp antibodies (OR = 3.4375, 95% CI = 1.04 to 11.25, p = 0.04). With this, we found a significant risk association for the SNV rs4958351 of the GRIA1 gene. On the other hand, we did not find significant risk associations for the GRIA1 rs6889909 and NFATC2 rs6021191 SNVs, although other populations have shown a significant risk. Discussion: Our study has some limitations, such as the small sample size, the heterogeneity in adverse events due to the patients' different regions of origin, and the limited ability to conduct a more detailed follow-up on pancreatitis. Additionally, since no significant associations were found between the NFATC2 rs6021191 and GRIA1 rs6889909 SNVs and the development of adverse events or the presence of antibodies due to the use of L-Asp, it is necessary to investigate new specific SNVs that may improve the efficacy and safety of treatment in Mexican children with ALL. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have suggested an association between blood inflammation-related factors and postherpetic neuralgia. However, the causal relationship between blood inflammation-related factors and postherpetic neuralgia remains unclear. Methods: We employed a bidirectional Two-sample Mendelian randomization (MR) analysis to explore the causal relationship between blood inflammation-related factors and postherpetic neuralgia. The instrumental variables were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. The instrumental variables of the blood inflammation-related factors come from the database numbers GCST004420 to GCST004460 and GCST90029070. Postherpetic neuralgia has 195,191 samples with a total of 16,380,406 single nucleotide polymorphisms (SNPs). MR analyses were performed using inverse-variance weighted, MR-Egger, and weighted median methods. Results: The MR results revealed a significant causal effect of Macrophage Inflammatory Protein 1 Beta (MIP1β) on reducing the risk of postherpetic neuralgia (95%CI = 0.492–0.991, p = 0.044). Additionally, higher levels of interleukin (IL)-10 (95%CI = 0.973–0.998, p = 0.019) and IL-12p70 (95%CI = 0.973–0.997, p = 0.013) were associated with a lower risk of postherpetic neuralgia. Other inflammatory markers showed no significant causal relationship with this condition. Conclusion: This study identifies MIP1β, IL-10, and IL-12p70 as potential therapeutic targets for preventing or treating postherpetic neuralgia, underscoring the need for further research in this area. [ABSTRACT FROM AUTHOR]

Acne is a prevalent inflammatory disease in dermatology, and its pathogenesis may be associated with inflammation, immunity, and other mechanisms. It commonly manifests in young individuals and frequently imposes a heavy economic, physical, and psychological burden on patients. Gut microbes and blood metabolites, as significant immune and inflammatory regulators in the body, have been hypothesized to form the "neurocutaneous axis." Nonetheless, the precise causal relationships among the gut microbes, circulating blood metabolites, and acne development have yet to be elucidated. This study employed bidirectional two-sample Mendelian randomization (MR) to probe the causal impacts of 412 distinct gut microbes and 249 blood metabolites on acne. Single nucleotide polymorphisms (SNPs), which are closely associated with gut microbes and blood metabolites, were utilized as instrumental variables. This approach was taken to discern whether these elements serve as pathogenic or protective factors in relation to acne. Furthermore, a mediation analysis encompassing gut microbes, blood metabolites, and acne was conducted to explore potential correlations between gut microbes and blood metabolites, as well as their cumulative effects on acne. This was done to substantiate the notion of causality. Bidirectional two-sample MR analysis revealed 8 gut bacteria, 6 bacterial metabolic abundance pathways determined by birdshot, and 8 blood metabolites significantly associated with acne. The mediation MR analysis revealed 2 potential causal relationships, namely, Bifidobacterium-DHA-Acne and Bifidobacterium-Degree of Unsaturation-Acne. This study identified gut microbes and blood metabolites that are causally associated with acne. A potential causal relationship between gut microbes and blood metabolites was obtained via mediation analysis. These insights pave the way for the identification of new targets and the formulation of innovative approaches for the prevention and treatment of acne. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a complex heterogenous disorder manifesting with various reproductive, endocrine, and metabolic derangements such as insulin resistance and hyperglycemia. The arginine vasopressin peptide (AVP), also called or antidiuretic hormone (ADH), modulates metabolic functions such as glucose hemostasis, insulin sensitivity, and lipid metabolism via binding to two central and peripheral receptors (AVPR1A and AVPR1B). In the present study, we aimed to detect whether the AVPR1A and AVPR1B genes confer risk for PCOS. Methods: In peninsular Italian families, we tested 7 variants in the AVPR1B gene and 2 variants in the AVPR1A gene via Pseudomarker for linkage and linkage joint to association (i.e.., linkage disequilibrium) with PCOS. Results: We identified two risk variants in each gene, significantly associated with the risk of PCOS. Conclusion: To the best of our knowledge, this is the first study to report risk variants in AVPR1A and AVPR1B genes in association with PCOS. However, replication in other ethnic groups as well as functional studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Background: PfAP2-EXP2 is located within chromosome 6 of Plasmodium falciparum recently identified to be undergoing an extensive selective sweep in West African isolates. The gene encoding this transcription factor, PfAP2-EXP2, is essential and thus likely subject to purifying selection that limits variants in the parasite population despite its genomic location. Methods: 72 Plasmodium falciparum field samples and 801 clinical sequences from the Pf6 MalariaGEN dataset of Ghanaian origin, were integrated and analysed. Results: A total of 14 single nucleotide variants of which 5 were missense variants, were identified after quality checks and filtering. Except for one, all identified variants were rare among the clinical samples obtained in this study (Minor allelic frequency < 0.01). Further results revealed a considerably low dN/dS value (0.208) suggesting the presence of purifying selection. Further, all the mutant amino acids were wildtype residues in AP2-EXP2 orthologous proteins—tentatively suggesting a genus-level conservation of amino acid residues. Computational analysis and predictions corroborated these findings. Conclusions: Despite the recent extensive selective sweep within chromosome 6 of West African isolates, PfAP2-EXP2 of Ghanaian origin exhibits low nucleotide diversity and very low dN/dS consistent with purifying selection acting to maintain the function of an essential gene. The conservation of AP2-EXP2 is an important factor that makes it a potential drug target. [ABSTRACT FROM AUTHOR]

Background: Lumpy Skin Disease (LSD) is endemic in sub-Saharan countries and is currently a global threat to the cattle industry. Information on the circulating Capripoxvirus lumpyskinpox, formerly known as Lumpy Skin Disease Virus (LSDV), and other poxviruses infecting cattle is very scant in Tanzania. The current study aimed to confirm and characterize LSDV and other poxviruses infecting cattle, from LSD suspected outbreaks in Tanzania. Methods: A total of 24 samples were collected from four LSD suspected outbreaks reported in Tanzania between February and May 2023. Samples were screened for LSDV genome by real-time PCR and then subjected to a high-resolution multiplex melting (HRM) assay where 10 samples were positive for Capripoxvirus (CaPV) and one sample was Parapoxvirus (PPV) positive. Four LSDV genes; RPO30, GPCR, EEV glycoprotein and B22R and the partial B2L gene of PPVs were analyzed. Results: All targeted LSDV genes from the Tanzanian isolates showed 100% similarity and isolates clustered with commonly circulating LSDV field isolates. Furthermore, the single nucleotide polymorphism (SNP) at position 240 (A-> G) of the EEV gene differentiates the Tanzanian LSDVs from the group of ancient Kenyan LSDV isolates while the B22R sequences of the Tanzanian LSDV isolates differed from the LSDV Neethling and LSDV KSGP-0240 derived vaccines. Sequence analysis of the partial B2L gene of the Tanzanian parapoxvirus bovinestomatitis, formerly known as Bovine papular stomatitis virus (BPSV) showed a different BPSV strain circulating compared to publicly available sequences. Conclusion: These findings confirm the presence of LSDV in Tanzania, which suggesting the need for establishing an effective control program and continuous monitoring. The presence of a typical profile for Tanzania BPSV is an indication that, although never reported before, BPSV is established in the country therefore this virus should be included in the differential diagnosis of LSDV. [ABSTRACT FROM AUTHOR]

Background: The study of rodent malaria parasites has significantly advanced our understanding of malaria parasite biology and host responses to parasite infections. There are four well-characterized rodent malaria parasite species (Plasmodium yoelii, P. chabaudi, P. berghei, and P. vinckei). Each species also has multiple strains that cause different disease phenotypes. P. yoelii nigeriensis N67C and N67, two isogenic parasites, are particularly intriguing as they differ in virulence and incite different immune responses in mice. The genome of the N67 parasite has been assembled recently, but not that of N67C. This study used PacBio HiFi sequencing data to assemble the N67C genome, compared the two genomes, and performed RNA sequencing to identify polymorphisms and differentially expressed genes (DEGs). Results: The assembled N67C parasite genome consisted of 16 scaffolds and three contigs of approximately 22.5 Mb with 100% and 96.6% completeness based on well-characterized single-copy orthologs specific to the Apicomplexa phylum and the Plasmodium genus, respectively. A comparison between the annotated N67C and N67 genomes revealed 133 single nucleotide polymorphisms (SNPs) and 75 indels. Among the polymorphic sites, an S (N67) to N (N67C) amino acid substitution at position 114 (S114N) in the dihydrofolate reductase-thymidylate synthase (DHFR-TS) confers resistance to pyrimethamine in mice. Additionally, 60 differentially expressed single-copy genes (DEGs) were detected after comparing mRNA levels between the two parasites. Starting with the predicted and annotated 5,681 N67C and 5,749 N67 genes, we identified 4,641 orthogroups that included at least one gene from the four P. yoelii parasites (N67, N67C, 17X, and YM), whereas 758 orthogroups showed subspecies or strain-specific patterns. Conclusion: The identification of polymorphic sites between the N67 and N67C genomes, along with the detection of the DEGs, may provide crucial insights into the variations in parasite drug responses and disease severity between these two isogenic parasites. The functional characterization of these genetic differences and candidate genes will deepen our understanding of disease mechanisms and pave the way for developing more effective control measures against malaria. [ABSTRACT FROM AUTHOR]

The current investigation was undertaken to elucidate the population-stratifying and ancestry-informative markers in Indian, Chinese, and wild yak populations using whole genome resequencing (WGS) analysis while employing various selection strategies (Delta, Pairwise Wright's Fixation Index-FST, and Informativeness of Assignment) and marker densities (5–25 thousand). The study used WGS data on 105 individuals from three separate yak cohorts i.e., Indian yak (n = 29), Chinese yak (n = 61), and wild yak (n = 15). Variant calling in the GATK program with strict quality control resulted in 1,002,970 high-quality and independent (LD-pruned) SNP markers across the yak autosomes. Analysis was undertaken in toolbox for ranking and evaluation of SNPs (TRES) program wherein three different criteria i.e., Delta, Pairwise Wright's Fixation Index-FST, and Informativeness of Assignment were employed to identify population-stratifying and ancestry-informative markers across various datasets. The top-ranked 5,000 (5K), 10,000 (10K), 15,000 (15K), 20,000 (20K), and 25,000 (25K) SNPs were identified from each dataset while their composition and performance was assessed using different criteria. The average genomic breed clustering of Indian, Chinese, and wild yak cohorts with full density dataset (105 individuals with 1,002,970 markers) was 81.74%, 80.02%, and 83.62%, respectively. Informativeness of Assignment criterion with 10K density emerged as the best combination for three yak cohorts with 86.94%, 96.46%, and 98.20% clustering for Indian, Chinese, and wild yak, respectively. There was an average increase of 7.56%, 22.72%, and 30.35% in genomic breed clustering scores of Indian, Chinese, and wild yak cohorts over the estimates of the original dataset. The selected markers showed overlap multiple protein-coding genes within a 10 kb window including ADGRB3, ANK1, CACNG7, CALN1, CHCHD2, CREBBP, GLI3, KHDRBS2, and OSBPL10. This is the first report ever on elucidating low-density SNP marker sets with population-stratifying and ancestry-informative properties in three yak groups using WGS data. The results gain significance for application of genomic selection using cost-effective low-density SNP panels in global yak species. [ABSTRACT FROM AUTHOR]

Background: Chronic myeloid leukaemia (CML) is a type of blood cancer that begins in the hematopoietic stem cells. It is primarily characterized by a specific chromosomal aberration, the Philadelphia chromosome. While the fusion gene is a major contributor to CML, several other genes including ADGRE2, that are reported as highly expressed in hematopoietic stem cells and could be utilized as a therapeutic marker in leukemic patients are implicated in the disease's progression. Until recently, little research had been conducted to identify single nucleotide polymorphisms (SNPs) associated with CML. Therefore, this study aims to investigate the influence of non-synonymous variants on the structure and function of the gene encoding adhesion G protein-coupled receptor E2, ADGRE2, and to evaluate their association with CML and its clinical and pathological characteristics. Methods: Non-synonymous SNPs of ADGRE2 were retrieved from the ENSEMBL, COSMIC, and gnomAD genome browsers, and the pathogenicity of deleterious variants was assessed using several established computational tools, including SIFT, CADD, REVEL, PolyPhen, and MetaLR. Results: Various in silico analyses explored the impact of damaging SNP on the function, stability, and structure of EGF-like modules containing mucin-like hormone receptor-like2 (EMR2) protein encoded by the ADGRE2 gene. Genotype analysis was performed on collected blood samples, revealing that altered genotype TT of variant rs765071211 (C/T) was associated significantly with CML patients compared to the control. Further in vitro and in vivo analyses suggest that this SNP holds potential for clinical translation. [ABSTRACT FROM AUTHOR]

Failure to consider population structure when managing harvested fishes increases the risk of stock depletion, yet empirical estimates of population structure are often lacking for important fishery species. In this study, we characterise genetic variation in single nucleotide polymorphisms (SNPs) to assess population structure for three harvested species of tropical snappers across the broad (up to 300 km wide) and extensive (~ 4000 km) continental shelf of north-western Australia. Comparisons across ~ 300 individuals per species, showed remarkably similar patterns of genetic structure among Lutjanus sebae (red emperor), L. malabaricus (saddletail snapper) and Pristipomoides multidens (goldband snapper) despite subtle differences in biological and ecological traits. Low levels of genetic subdivision were reflected in an isolation by distance relationship where genetic connectivity increased with geographic proximity. This indicates extensive but not unlimited dispersal across the north-western Australian shelf. Our findings provide evidence of connectivity between current management areas, violating the assumption of multiple independent stocks. Spatial stock assessment models may be more suitable for the management of these species however demographic connectivity rates cannot be accurately estimated from the conventional population genetic approaches applied in this study. We recommend that managers aim to maintain adequate spawning biomass across current management areas, and assess stocks at finer scales, where practical. [ABSTRACT FROM AUTHOR]

Utilizing the full potential of rice collections mainly depends on an in‐depth exploration and understanding of the vast diversity in its germplasm. The AfricaRice genebank holds the largest collection of rice germplasm originating from the African continent. In the present study, we comprehensively characterized a collection of 9013 accessions, including Oryza barthii A. Chev., Oryza glaberrima Steud., Oryza longistaminata A. Chev. & Roehr., Oryza sativa L. ssp. indica, and Oryza sativa L. ssp. japonica, for genetic diversity and population structure using genotyping‐by‐sequencing through DArTseq analysis. We identified 27,718 high‐quality single nucleotide polymorphism markers after the genotypic data were filtered. Based on the analyses, the collection has extensive genetic diversity, and the average genetic distance of the entire set was 0.267 (range 0.001–0.469), with 45.1% of pairs of accessions being highly distant and 40.1% moderately distant from each other. Neighbor‐joining tree, principal component, and Bayesian population structure analyses clustered the 9013 accessions into six groups, based roughly on their taxonomic and biological status. The first, second, and third groups consisted of accessions belonging to O. glaberrima, O. barthii, and O. longistaminata, respectively. The fourth, fifth, and sixth groups were improved‐indica, japonica, and traditional‐indica accessions, respectively. The highest value of genetic variance proportion (PhiPT) was found in the species group followed by groups based on cluster analysis and on Bayesian population structure at K = 6. These results allow us to better understand the genetic diversity present in 9013 rice accessions maintained in the AfricaRice genebank and offer a valuable tool for pre breeding, breeding, and further genetic applications. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Objectives Methods Results Conclusion Observational studies have shown a bidirectional association between gastroesophageal reflux (GER) and chronic rhinosinusitis (CRS) or chronic rhinitis (CR), but it is not clear whether this association is causal.This study was to investigate the causality between GER and CRS or CR using bidirectional two‐sample Mendelian randomization (MR) analysis.Using pooled data from large genome‐wide association studies (GWAS), genetic loci independently associated with GER, CRS and CR in populations of European and American ancestry were selected as instrumental variables (IVs). The inverse variance weighted (IVW) method was used to analyse the random effects model of MR, and the odds ratio (OR) was used as the evaluation index to explore the bidirectional causality between GER and CRS or CR. Single nucleotide polymorphism (SNP) outliers were detected using MR‐pleiotropy Residual Sum and Outliers (MR‐PRESSO). The MR–Egger intercept test examined the horizontal pleiotropy of SNPs. The “leave‐one‐out” sensitivity analysis examined whether MR results were affected by a single SNP.The main results of IVW showed that GER increased the risk of CRS (OR = 1.3795, 95% CI = 1.188–1.603, p < 0.0500) and CR (OR = 1.3941, 95% CI = 1.1671–1.6652, p < 0.0500). The obtained SNPs as IVs for GER, CRS and CR had no significant horizontal pleiotropy, heterogeneity or bias. Regarding the reverse directions, no notable associations could be found.This MR analysis revealed that genetically predicted GER had a causal effect on an increased risk of CRS or CR, but not vice versa. These results have great implications for the management of CRS (especially for refractory CRS) or CR in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: With its distinctive evolutionary rate and inheritance patterns separate from the nuclear genome, mitochondrial genome analysis has become a prominent focus of current research. Dendrobium hancockii Rolfe, a species of orchid with both medicinal and horticultural value, will benefit from the application of the fully assembled and annotated mitochondrial genome. This will aid in elucidating its phylogenetic relationships, comparative genomics, and population genetic diversity. Methods: Based on sequencing results from Illumina combined with PacBio and Nanopore, the mitochondrial genome map of D. hancockii was constructed. Comparative analysis was conducted from the perspectives of phylogeny across multiple species, selection pressure on protein-coding genes, and homologous segments. The population diversity of D. hancockii was analyzed using single nucleotide polymorphism (SNP) data from the mitochondrial genome and single-copy nuclear genes. Results and discussion: This research constructed a circular mitochondrial map for D. hancockii , spanning 523,952 bp, containing 40 unique protein-coding genes, 37 transfer RNA genes, and 4 ribosomal RNA genes. Comparative analysis of mitochondrial genes from 26 land plants revealed a conserved gene cluster, " rpl16-ccmFn-rps3-rps19 ," particularly within the Dendrobium genus. The mitochondrial genome of D. hancockii exhibits a lower point mutation rate but significant structural variation. Analysis of 103 resequencing samples identified 19,101 SNP sites, dividing D. hancockii into two major groups with limited gene flow between them, as supported by population diversity, genetic structure analysis, principal component analysis, and phylogenetic trees. The geographical distribution and genetic differentiation of D. hancockii into two major groups suggest a clear phytogeographical division, likely driven by ancient geological or climatic events. The close alignment of mitochondrial data with nuclear gene data highlights the potential of the mitochondrial genome for future studies on genetic evolution in this species. [ABSTRACT FROM AUTHOR]

Sorghum is an important source of food and feed worldwide. Developing sorghum core germplasm collections improves our understanding of the evolution and exploitation of genetic diversity in breeding programs. Despite its significance, the characterization of the genetic diversity of local germplasm pools and the identification of genomic loci underlying the variation of critical agronomic traits in sorghum remains limited in most African countries, including Uganda. In this study, we evaluated a collection of 543 sorghum accessions actively used in Ugandan breeding program across two cropping seasons at NaSARRI, Uganda, under natural field conditions. Phenotypic data analysis revealed significant (p <0.01) variation among accessions for days to 50% flowering, plant height, panicle exsertion, and grain yield, with broad-sense heritability (H²) estimates of 0.54, 0.9, 0.81, and 0.48, respectively, indicating a high genetic variability for these traits. We used a newly developed genomic resource of 7,156 single nucleotide polymorphism (SNP) markers to characterize the genetic diversity and population structure of this collection. On average, the SNP markers exhibited moderately high polymorphic information content (PIC = 0.3) and gene diversity (He = 0.3), while observed heterozygosity (Ho = 0.07) was low, typical for self-pollinating crops like sorghum. Admixture-based models, PCA, and cluster analysis all grouped the accessions into two subpopulations with relatively low genetic differentiation. Genome-wide association study (GWAS) identified candidate genes linked to key agronomic traits using a breeding diversity panel from Uganda. GWAS analysis using three different mixed models identified 12 genomic regions associated with days to flowering, plant height, panicle exsertion, grain yield, and glume coverage. Five core candidate genes were co-localized with these significant SNPs. The SNP markers and candidate genes discovered provide valuable insights into the genetic regulation of key agronomic traits and, upon validation, hold promise for genomics-driven breeding strategies in Uganda. [ABSTRACT FROM AUTHOR]

Objective: The pathogenesis of antituberculosis drug-induced liver injury (AT-DILI) remains largely unknown. The current investigation aimed to determine the genetic contribution of the nuclear receptor subfamily 1 Group I member 3 (NR1I3) and nuclear receptor subfamily 1 Group H member 4 (NR1H4) genes to the risk of AT-DILI in the Chinese population. Methods: A 1:4 matched case‒control study was conducted, and five single nucleotide polymorphisms (SNPs) in the NR1I3 and NR1H4 genes were detected and assessed. Utilizing a multivariate conditional logistic regression model, the effects of haplotype and genotype on the risk of AT-DILI were examined. Extended subgroup analysis was carried out based on sex. The distribution of the peak value of serum liver enzymes also compared among different genotypes. Results: 224 AT-DILI cases and 896 controls were included in this study. No significant difference was observed in genotypes or haplotypes frequencies between AT-DILI cases and controls. However, comparisons of liver function indicators revealed significant differences in the peak values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) among patients with different genotypes of NR1H4 rs56163822 (GG vs. GT vs. TT, 27.1 U/L vs. 26.0 U/L vs. 23.0 U/L, p = 0.020; 34.0 U/L vs. 31.0 U/L vs. 30.6 U/L, p = 0.008; 15.5 μmol/L vs. 15.0 μmol/L vs. 13.7 μmol/L, p = 0.029, respectively), as well as in the peak values of ALT and AST among male patients with different genotypes of NR1H4 rs56163822 (29.0 U/L vs. 26.9 U/L vs. 22.6 U/L, p = 0.002; 34.0 U/L vs. 32.0 U/L vs. 30.5 U/L, p = 0.019, respectively). Conclusion: Based on this 1:4 individual-matched case‒control study, the SNP rs56163822 in the NR1H4 gene may be linked to the susceptibility to AT-DILI in Chinese patients receiving anti-TB treatment. Further studies in larger varied populations are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Background: In Mexico, 75% of diabetes mellitus type 2 (DMT2) patients are not in glycaemic control criteria (HbA1c<7%); this entails a significantly variable drug response. Amongst the factors influencing such variability, are genetics, more specifically, single nucleotide polymorphisms (SNPs). Three genes implied in metformin pharmacokinetics are SLC22A1 , SLC22A2 , and SLC22A3 , which are polymorphic. While there have been cross-sectional studies on their SNPs impact over drug response, a longitudinal study would contribute valuable information on their effect over time. Methods: SNPs of SLC22A1 (rs72552763, rs622342, rs12208357, rs2282143, rs594709, rs628031, and rs683369), SLC22A2 (rs316019), and SLC22A3 (rs2076828), were determined through PCR-TR. The clinical records of 69 patients undergoing metformin monotherapy were retrospectively assessed. Metformin is the first line treatment against DMT2. A level of HbA1c <7% (time 0) was considered as an inescapable inclusion criterion. The study's cases were those patients who reported HbA1c ≥ 7% (time1) after time 0 (t0). Kaplan-Meier curves including a Log-Rank test and a Cox multivariate analysis of proportional risks were performed. Aim: Determining clinical, biochemical, and genetic variables which may affect non-control (HbA1c ≥ 7%) survival time spans amongst DMT2 Mexican-Mestizo patients undergoing metformin monotherapy at Hospital Regional de Alta Especialidad de Ixtapaluca (HRAEI) between October 2013 and December 2023. Results: All 69 patients were monitored over a median period of 642 days (273-1,134). A comparison between time 0 and time 1 (t1) revealed differences in weight (p = 0.036), metformin dose mg/kg/day (p = 0.003), plasmatic glucose mg/dL (p = 0.048), and HbA1c (p < 0.001). The median non-control survival rate was different across the 3 genotypes of rs62552763 in SLC22A1 (p = 0.0034) and the dominant genotypic model GAT/GAT vs. GAT/del + del/del (p = 0.009). There were differences between rs622342 genotypes as well (p = 0.041). In GAT/GAT the Cox model found HR = 0.407 (IC95%: 0.202–0.818, p = 0.011) in the univariate analysis and HR = 0.418 (IC95%: 0.204–0.856, p = 0.034) in the multivariate analysis, adjusted by initial metformin dose (mg/kg/day), initial weight (kg), and final metformin dose (mg/kg/day). Genotype A/A of rs622342 in SLC22A1 , reported HR = 0.392 (IC95%: 0.169–0.910, p = 0.029) in the multivariate analysis as well. Conclusion: Among DMT2 Mexican-Mestizo patients undergoing metformin monotherapy the minor allele del in rs72552763 and the minor allele C in rs622342 reported a significantly shorter survival median respect to the wild type variant. Patients carrying del in rs72552763 or C in rs622342, both in SLC22A1 , will reach non-control in less time with respect to other patients. Therefore these genotypes may constitute a therapeutic response biomarker for this population. [ABSTRACT FROM AUTHOR]

Background: The influence of pharmacogenomics on opioid response, particularly with COMT (rs4680) and OPRM1 (rs1799971) variants, has been studied individually and in combination. However, most studies are in a noncancer context and not all their possible variant combinations have been examined. Objectives: This study examined COMT (rs4680) and OPRM1 (rs1799971), and their allele combinations, in advanced cancer to examine associations with pain scores, opioid dose, and adverse effects. Setting/Subjects: This multicenter prospective cohort study recruited patients receiving opioids for advanced cancer pain in Melbourne, Australia. Clinical data (demographics, opioids), validated instruments (pain and adverse effects), and blood (DNA) were collected. Descriptive analyses were used. Univariate and multivariate logistic regression analyses were used to evaluate associations between clinical outcomes (opioid dose, pain, adverse effects) and genotypes of interest. Results: Fifty-four participants were recruited to the study. Those with COMT A allele required lower opioid doses [130 mg (interquartile range [IQR] 67.5,230) versus 180 mg (IQR 55,322.5), p = 0.047] and experienced greater adverse effects [sickness response aOR (adjusted odds ratio) 7.1 (95% CI 1.51,33.41), p = 0.01]. Those with the COMT GG/OPRM1 G allele combination required higher opioid doses [322.5 mg (IQR 264,360) versus 125 mg (65,225), (p = 0.04)]. Those with COMT AG/OPRM1 AA experienced higher average pain [aOR 1.55 (95% CI 1.03, 2.33), p = 0.04] and moderate–severe nausea [aOR 5.47 (95% CI 1.35, 22.21), p = 0.02] but reduced drowsiness [aOR 0.25 (95% CI 0.06, 1.02), p = 0.05]. Conclusions: Patients with cancer with the COMT alternate (A) allele have greater sickness response adverse effects, which may be responsible for the lower opioid doses observed. Significant results of two new COMT/OPRM1 genotype combinations are presented that have not previously been studied, with plausible phenotype descriptions suggested. [ABSTRACT FROM AUTHOR]

Introduction: Individuals who develop new‐onset diabetes have been identified as a high‐risk cohort for pancreatic cancer (PC), exhibiting an incidence rate nearly 8 times higher than the general population. Hence, the targeted screening of this specific cohort presents a promising opportunity for early pancreatic cancer detection. We aimed to develop and validate a novel model capable of identifying high‐risk individuals among those with new‐onset diabetes. Methods: Employing the UK Biobank cohort, we focused on those developing new‐onset diabetes during follow‐up. Genetic and clinical characteristics available at registration were considered as candidate predictors. We conducted univariate regression analysis to identify potential indicators and used a 5‐fold cross‐validation method to select optimal predictors for model development. Five machine learning algorithms were used for model development. Results: Among 12,735 patients with new‐onset diabetes, 100 (0.8%) were diagnosed with PC within 2 years. The final model (area under the curve, 0.897; 95% confidence interval, 0.865–0.929) included 5 clinical predictors and 24 single nucleotide polymorphisms. Two threshold cut‐offs were established: 1.28% and 5.26%. The recommended 1.28% cut‐off, based on model performance, reduces definitive testing to 13% of the total population while capturing 76% of PC cases. The high‐risk threshold is 5.26%. Utilizing this threshold, only 2% of the population needs definitive testing, capturing nearly half of PC cases. Conclusions: We, for the first time, combined clinical and genetic data to develop and validate a model to determine the risk of pancreatic cancer in patients with new‐onset diabetes using machine learning algorithms. By reducing the number of unnecessary tests while ensuring that a substantial proportion of high‐risk patients are identified, this tool has the potential to improve patient outcomes and optimize healthcare sources. [ABSTRACT FROM AUTHOR]

In genomics, use of deep learning (DL) is rapidly growing and DL has successfully demonstrated its ability to uncover complex relationships in large biological and biomedical data sets. With the development of high-throughput sequencing techniques, genomic markers can now be allocated to large sections of a genome. By analyzing allele sharing between individuals, one may calculate realized genomic relationships from single-nucleotide polymorphisms (SNPs) data rather than relying on known pedigree relationships under polygenic model. The traditional approaches in genome-wide prediction (GWP) of quantitative phenotypes utilize genomic relationships in fixed global covariance modeling, possibly with some nonlinear kernel mapping (for example Gaussian processes). On the other hand, the DL approaches proposed so far for GWP fail to take into account the non-Euclidean graph structure of relationships between individuals over several generations. In this paper, we propose one global convolutional neural network (GCN) and one local sub-sampling architecture (GCN-RS) that are specifically designed to perform regression analysis based on genomic relationship information. A GCN is tailored to non-Euclidean spaces and consists of several layers of graph convolutions. The GCN-RS architecture is designed to further improve the GCN's performance by sub-sampling the graph to reduce the dimensionality of the input data. Through these graph convolutional layers, the GCN maps input genomic markers to their quantitative phenotype values. The graphs are constructed using an iterative nearest neighbor approach. Comparisons show that the GCN-RS outperforms the popular Genomic Best Linear Unbiased Predictor method on one simulated and three real datasets from wheat, mice and pig with a predictive improvement of 4.4% to 49.4% in terms of test mean squared error. This indicates that GCN-RS is a promising tool for genomic predictions in plants and animals. Furthermore, GCN-RS is computationally efficient, making it a viable option for large-scale applications. [ABSTRACT FROM AUTHOR]

Background: Inter-individual differences in treatment response are marked in multiple sclerosis (MS). This is true for Natalizumab (NTZ), to which a subset of patients displays sub-optimal treatment response. We conducted a multi-centric genome-wide association study (GWAS), with additional pathway and network analysis to identify genetic predictors of response to NTZ. Methods: MS patients from three different centers were included. Response to NTZ was dichotomized, nominating responders (R) relapse-free patients and non-responders (NR) all the others, over a follow-up of 4 years. Association analysis on ~ 4.7 M imputed autosomal common single-nucleotide polymorphisms (SNPs) was performed fitting logistic regression models, adjusted for baseline covariates, followed by meta-analysis at SNP and gene level. Finally, these signals were projected onto STRING interactome, to elicit modules and hub genes linked to response. Results: Overall, 1834 patients were included: 119 from Italy (R = 94, NR = 25), 81 from Germany (R = 61, NR = 20), and 1634 from Sweden (R = 1349, NR = 285). The top-associated variant was rs11132400T (p = 1.33 × 10–6, OR = 0.58), affecting expression of several genes in the locus, like KLKB1. The interactome analysis implicated a module of 135 genes, with over-representation of terms like canonical WNT signaling pathway (padjust = 7.08 × 10–6). Response-associated genes like GRB2 and LRP6, already implicated in MS pathogenesis, were topologically prioritized within the module. Conclusion: This GWAS, the largest pharmacogenomic study of response to NTZ, suggested MS-implicated genes and Wnt/β-catenin signaling pathway, an essential component for blood–brain barrier formation and maintenance, to be related to treatment response. [ABSTRACT FROM AUTHOR]

Introduction: Matrix Metalloproteinase 3 (MMP3) is a vital member of the MMP family, known for its wide range of substrate specificity and proteolytic activity against Extracellular Matrix (ECM) components. The role of functional polymorphisms in the MMP genes has been previously investigated in relation to cancer susceptibility, particularly breast cancer. Several Single- Nucleotide Polymorphisms (SNPs) in the MMP3 gene have been linked to a number of clinical illnesses, such as Coronary Artery Disease (CAD); however, the results were not entirely conclusive. Aim: To identify pathogenic missense SNPs in the human MMP3 gene and analyse their effects on structure and function. Materials and Methods: This was a record-based cross-sectional study performed using data retrieved from online resources. The analysis was conducted using a series of different bioinformatic tools, for which ethical clearance was obtained from the institution. The online tools used included Sorting Intolerant from Tolerant (SIFT), PolyPhen-2, PhD-SNP, PANTHER, PROVEAN, and SNPs and GO to predict harmful non synonymous SNPs (nsSNPs). Further analysis was performed using I-Mutant 2.0, MutPred2, Consurf, and HOPE software. These tools were able to filter out damaging SNPs and predict the impact of deleterious SNPs on the structure and function of the MMP3 protein. Results: This study predicted two potentially pathogenic SNPs (D175Y and Y116C) out of 443 missense SNPs from dbSNP, which is a database of SNPs available on the National Centre for Biotechnology Information website. Further analysis revealed that these SNPs were located in highly conserved regions and were predicted to decrease protein stability. Conclusion: In this study, two potentially pathogenic SNPs (D175Y and Y116C) were identified. Characterisation of these SNPs can help us gain a better understanding of the molecular basis of clinical conditions. The results of this study can be further validated by designing population-based studies and wet lab experiments. This will help in augmenting research and personalised medicine. [ABSTRACT FROM AUTHOR]

The extracellular isoform of superoxide dismutase (SOD3) is decreased in patients and animals with pulmonary hypertension (PH). The human R213G single-nucleotide polymorphism (SNP) in SOD3 causes its release from tissue extracellular matrix (ECM) into extracellular fluids, without modulating enzyme activity, increasing cardiovascular disease risk in humans and exacerbating chronic hypoxic PH in mice. Given the importance of interstitial macrophages (IMs) to PH pathogenesis, this study aimed to determine whether R213G SOD3 increases IM accumulation and alters IM reprogramming in response to hypoxia. R213G mice and wild-type (WT) controls were exposed to hypobaric hypoxia for 4 or 14 days compared with normoxia. Flow cytometry demonstrated a transient increase in IMs at day 4 in both strains. Contrary to our hypothesis, the R213G SNP did not augment IM accumulation. To determine strain differences in the IM reprogramming response to hypoxia, we performed RNAsequencing on IMs isolated at each timepoint. We found that IMs from R213G mice exposed to hypoxia activated ECM-related pathways and a combination of alternative macrophage and proinflammatory signaling. Furthermore, when compared with WT responses, IMs from R213G mice lacked metabolic remodeling and demonstrated a blunted anti-inflammatory response between the early (day 4) and later (day 14) timepoints. We confirmed metabolic responses using Agilent Seahorse assays, whereby WT, but not R213G, IMs upregulated glycolysis at day 4 that returned to baseline at day 14. Finally, we identify differential regulation of several redox-sensitive upstream regulators that could be investigated in future studies. NEW & NOTEWORTHY: Redistributed expression of SOD3 out of tissue ECM due to the human R213G SNP exacerbates chronic hypoxic PH. Highlighting the importance of macrophage phenotype, our findings reveal that the R213G SNP does not exacerbate pulmonary macrophage accumulation in response to hypoxia but influences their metabolic and phenotypic reprogramming. We demonstrate a deficiency in the metabolic response to hypoxic stress in R213G macrophages, associated with weakened inflammatory resolution and activation of profibrotic pathways implicated in PH. [ABSTRACT FROM AUTHOR]

Numerous studies have established associations between single nucleotide polymorphisms (SNPs) and various behavioral and neurodevelopmental conditions. This study explores the links between SNPs in candidate genes involved in central nervous system (CNS) physiology and their implications for the behavioral and emotional aspects in children and teenagers. A total of 590 participants, aged 7–15 years, from the Early Life Exposures In Mexico To Environmental Toxicants (ELEMENT) cohort study in Mexico City, underwent genotyping for at least one of 15 CNS gene‐related SNPs at different timepoints. We employed multiple linear regression models to assess the potential impact of genetic variations on behavioral and cognitive traits, as measured by the Behavioral Assessment System for Children (BASC) and Conners parent rating scales. Significant associations were observed, including the rs1800497 TC genotype (ANKK1) with the Cognitive Problems/Inattention variable (p value = 0.003), the rs1800955 CT genotype (DDR4) with the Emotional Lability Global index variable (p value = 0.01), and the rs10492138 GA and rs7970177 TC genotypes (GRIN2B) with the Depression variable (p values 0.007 and 0.012, respectively). These finds suggest potential genetic profiles associated with "risk" and "protective" behaviors for these SNPs. Our results provide valuable insights into the role of genetic variations in neurobehavior and highlight the need for further research in the early identification and intervention in individuals at risk for these conditions. [ABSTRACT FROM AUTHOR]

Head and neck cancer is the seventh leading cancer diagnosis worldwide. One of the most common cancers in the head and neck region is laryngeal cancer. In past years, the incidence of laryngeal squamous cell carcinoma has risen by 23%, and despite progress in treatment modalities, the survival rate has not changed. It is well known that genetic alterations may contribute to individuals' susceptibility to cancer. Research of genetic alterations, such as single nucleotide polymorphisms, is essential to understanding carcinogenesis and susceptibility of laryngeal squamous cell carcinoma. A total of 200 LSCC patients and 200 controls were included in this retrospective case-control study; both groups were matched by age and sex. In the present study, we analyzed six SNPs in genes essential for apoptosis regulation: TP53 (rs9895829, rs17884306), BCL2 (rs1564483, rs4987855), BAX (rs704243), NOXA (PMAIP1) (rs1041978, rs78800940). We evaluated their associations with the risk of LSCC development, its pathomorphological manifestation, and patients' overall survival rate. Genotyping was carried out using RT-PCR. The AG genotype of rs9895829 was more prevalent in controls than in cancer patients, leading to lower susceptibility to LSCC (OR = 0.301; 95%CI 0.096–0.940; p = 0.039). None of the analyzed SNPs showed an association with pathomorphological features of LSCC, but NOXA rs1041978 T allele carriers were found to be diagnosed with LSCC at an older age (OR = 1.962; 95%CI 1.072–3.592; p = 0.031). There was no statistically significant association between investigated SNPs and patient OS. The present study indicates that the AG genotype of rs9895829 provides a protective effect against LSCC development. [ABSTRACT FROM AUTHOR]

This study utilized 303 pepper accessions from diverse Capsicum species to explore fruit traits, including length, width, wall thickness, and weight. Descriptive statistics revealed a mean fruit length of 66.19 mm, width of 23.48 mm, wall thickness of 1.89 mm, and weight of 15.29 g, with significant variability, particularly in fruit weight. Correlation analysis demonstrated strong positive relationships between fruit width, weight, and fruit wall thickness (r = 0.89 and r = 0.86, respectively), while fruit length showed weaker correlations with these traits. Analysis of fruit positions revealed that the majority of accessions had a pendent fruit position (156), followed by erect (85) and intermediate (8). In terms of fruit shape, triangular and narrow triangular shapes were the most common, observed in 102 and 98 accessions, respectively. Genome-wide association studies (GWAS) identified significant single nucleotide polymorphisms (SNPs) associated with fruit traits across four models (Blink, FarmCPU, MLM, MLMM). The number of significantly associated SNPs were as follows: fruit length (89), fruit width (55), fruit weight (63), fruit wall thickness (48), fruit shape (151), and fruit position (51). Several genes were also identified where the SNPs are located or adjacent to, providing candidate genes for further exploration of the genetic basis of fruit morphology. Notably, genes such as E3 ubiquitin-protein ligase RGLG1 (associated with fruit width), Homeobox-leucine zipper protein HDG11 (involved in fruit width), Auxin response factor 23 (linked to fruit shape), and ATP-dependent zinc metalloprotease FtsH (related to fruit weight) were identified. These findings enhance our understanding of the genetic basis of fruit morphology in Capsicum, offering valuable insights for breeding and agricultural practices. [ABSTRACT FROM AUTHOR]

Sweet potato (Ipomoea batatas) is an important food crop that plays a pivotal role in preserving worldwide food security. Due to its polyploid genome, high heterogeneity, and phenotypic plasticity, sweet potato genetic characterization and breeding is challenging. Genome-wide association studies (GWASs) can provide important resources for breeders to improve breeding efficiency and effectiveness. GWASpoly was used to identify 28 single nucleotide polymorphisms (SNPs), comprising 21 unique genetic loci, associated with sweet potato storage root traits including dry matter (4 loci), subjective flesh color (5 loci), flesh hue angle (3 loci), and subjective skin color and skin hue angle (9 loci), in 384 accessions from the USDA sweet potato germplasm collection. The I. batatas 'Beauregard' and I. trifida reference genomes were utilized to identify candidate genes located within 100 kb from the SNPs that may affect the storage traits of dry matter, flesh color, and skin color. These candidate genes include transcription factors (especially Myb, bHLH, and WRKY family members), metabolite transporters, and metabolic enzymes and associated proteins involved in starch, carotenoid, and anthocyanin synthesis. A greater understanding of the genetic loci underlying sweet potato storage root traits will enable marker-assisted breeding of new varieties with desired traits. This study not only reinforces previous research findings on genes associated with dry matter and β-carotene content but also introduces novel genetic loci linked to these traits as well as other root characteristics. [ABSTRACT FROM AUTHOR]

The Ningxiang pig, one of the well-known Chinese native pig breeds, has the advantages of tender meat, high intramuscular fat (IMF) content, and roughage tolerance, compared to the commercial lean pig breeds. The genetic basis for complex traits in Ningxiang pigs has been previously studied through other genetic markers, such as Single Nucleotide Polymorphism (SNP), while the characteristics of copy number variation (CNV) and the selection signal have not been investigated yet. In this study, GGP 50 k genotyping data of 2242 Ningxiang pigs (NX) and 1137 Duroc pigs (Duroc) were involved in CNV atlas construction and selection signals identification. Annotations of genes and quantitative trait locus (QTLs) were performed on the target candidate regions, as follows: (1) 162 CNVs were detected in Ningxiang pigs, while 326 CNVs were detected in Duroc pigs, and there are 21 copy number variation regions (CNVRs) shared between them; (2) The CNVRs of Duroc are more abundant, with 192 CNVRs, accounting for 1.61% of the entire genome, while those of Ningxiang pigs only have 98 CNVRs, accounting for 0.49%; (3) The QTLs annotated on CNVs and selected regions of Ningxiang pigs were mainly associated with meat quality and fertility. In contrast, the Duroc QTLs' notes relate primarily to the carcass and immunity, and explain why they have a higher slaughter rate and immunity; (4) There is a presence of high-frequency acquired CNVs, specifically in Ningxiang pigs, with 24 genes significantly enriched in the sensory receptor-related pathway in this region; (5) Based on the CNVs atlas, candidate genes such as 3 inositol 1,4,5-triphosphate receptor, type 3 (ITPR3), forkhead box protein K2 (FOXK2), G-protein coupled estrogen receptor 1 (GPER1), Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), triosephosphate isomerase 1 (TPI1), and other candidate genes related to fat deposition and differentiation were screened. In general, this study improved our knowledge about copy number variation and selection signal information of Ningxiang pigs, which can not only further explain the genetic differences between Chinese native and Western commercial pig breeds, but also provide new materials for the analysis of the genetic basis of complex traits. [ABSTRACT FROM AUTHOR]

Preterm birth (PTB) forms a heterogeneous group with possible genetic predisposition. 25(OH)-vitamin D3 plays a significant role during implantation, placentation, and the maintenance of normal pregnancy. The aim of our research was to examine whether FokI, Cdx2, and ApaI VDR gene variants, as well as serum concentrations of 25-hydroxy25(OH)-vitamin D3 in women and their newborns, might be predisposing factors for idiopathic spontaneous preterm birth. The patient group consisted of 44 pairs of women with ISPTB and their children, and the control group consisted of 44 pairs of women who delivered at term and their children. At the time of delivery, peripheral blood was collected from every woman, and after newborn delivery, umbilical cord blood was collected. For genotyping of the rs2228570 C/T, rs11568820 G/A, and rs7975232 T/G SNPs, a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used. Serum concentrations of 25(OH)-vitamin D3 were determined using high-performance liquid chromatography (HPLC). There were no statistically significant differences in the frequencies of VDR genotypes and alleles between women with ISPTB and control women. There was a statistically significant difference in the distribution of VDR Cdx-2 (rs11568820) genotypes between preterm-born children and controls, with the GG genotype and G allele being more prevalent among patients than controls (p < 0.001). There were no statistically significant differences in mean values between women with ISPTB and control women, nor between preterm and full-term newborns, although the 25(OH)-vitamin D3 concentrations in preterm-born children were lower than in controls. Furthermore, there was a statistically significant correlation in 25(OH)-vitamin D3 concentrations between mothers and children both in the patient and in the control groups (b = 0.771, p < 0.001). The results of our study demonstrate a notable association between the VDR Cdx2 gene polymorphism and idiopathic spontaneous preterm birth (ISPTB) in a Caucasian population, but because of the small number of participants, further research is needed. [ABSTRACT FROM AUTHOR]

Beyond the essential role of p27Kip1 and cyclin D2 in cell cycle progression, they are also shown to confer an anti-apoptotic function in peripheral blood (PB) lymphocytes. Although the aberrant longevity and expression of p27Kip1 and cyclin D2 in leukemic cells is well documented, the exact mechanisms responsible for this phenomenon have yet to be elucidated. This study was undertaken to determine the associations between polymorphisms in the CDKN1B and CCND2 genes (encoding p27Kip1 and cyclin D2, respectively) and susceptibility to chronic lymphocytic leukemia (CLL), as well as their influence on the expression of both cell cycle regulators in PB leukemic B cells and non-malignant T cells from untreated CLL patients divided according to the genetic determinants studied. Three CDKN1B single-nucleotide polymorphisms (SNPs), rs36228499, rs34330, and rs2066827, and three CCND2 SNPs, rs3217933, rs3217901, and rs3217810, were genotyped using a real-time PCR system. The expression of p27Kip1 and cyclin D2 proteins in both leukemic B cells and non-malignant T cells was determined using flow cytometry. We found that the rs36228499A and rs34330T alleles in CDKN1B and the rs3217810T allele in the CCND2 gene were more frequent in patients and were associated with increased CLL risk. Moreover, we observed that patients possessing the CCND2rs3217901G allele had lower susceptibility to CLL (most pronounced in the AG genotype). We also noticed that the presence of the CDKN1Brs36228499CC, CDKN1Brs34330CC, CDKN1Brs2066827TT, and CCND2rs3217901AG genotypes shortened the time to CLL progression. Statistically significant functional relationships were limited to T cells and assigned to CDKN1B polymorphic variants; carriers of the polymorphisms rs34330CC and rs36228499CC (determining the aggressive course of CLL) expressed a decrease in p27Kip1 and cyclin D2 levels, respectively. We indicate for the first time that genetic variants at the CDKN1B and CCND2 loci may be considered as a potentially low-penetrating risk factor for CLL and determining the clinical outcome. [ABSTRACT FROM AUTHOR]