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Purpose: To investigate the causality between periodontitis and non-alcoholic fatty liver disease (NAFLD) using a two-sample bidirectional Mendelian randomisation (MR) analysis. Materials and Methods: Genetic variations in periodontitis and NAFLD were acquired from genome-wide association studies (GWAS) using the Gene-Lifestyle Interaction in Dental Endpoints, a large-scale meta-analysis, and FinnGen consortia. Data from the first two databases were used to explore the causal relationship between periodontitis and NAFLD (“discovery stage”), and the data from FinnGen was used to validate our results (“validation stage”). We initially performed MR analysis using 5 single nucleotide polymorphisms (SNPs) in the discovery samples and 18 in the replicate samples as genetic instruments for periodontitis to investigate the causative impact of periodontitis on NAFLD. We then conducted a reverse MR analysis using 6 SNPs in the discovery samples and 4 in the replicate samples as genetic instruments for NAFLD to assess the causative impact of NAFLD on periodontitis. We further implemented heterogeneity and sensitivity analyses to assess the reliability of the MR results. Results: Periodontitis was not causally related to NAFLD (odds ratio [OR] = 1.036, 95% CI: 0.914–1.175, p = 0.578 in the discovery stage; OR = 1.070, 95% CI: 0.935–1.224, p = 0.327 in the validation stage), and NAFLD was not causally linked with periodontitis (OR = 1.059, 95% CI: 0.916–1.225, p = 0.439 in the discovery stage; OR = 0.993, 95% CI: 0.896–1.102, p = 0.901 in the validation stage). No heterogeneity was observed among the selected SNPs. Sensitivity analyses demonstrated the absence of pleiotropy and the reliability of our MR results. Conclusion: The present MR analysis showed no genetic evidence for a cause-and-effect relationship between periodontitis and NAFLD. Periodontitis may not directly influence the development of NAFLD and vice versa. [ABSTRACT FROM AUTHOR]

[This corrects the article DOI: 10.3389/fmicb.2023.1154664.].

Atrial fibrillation (AF), the most common arrhythmia, has been associated with different electrophysiological, molecular, and structural alterations in atrial cardiomyocytes. Therefore, more studies are required to elucidate the genetic and molecular basis of AF. Various genome-wide association studies (GWAS) have strongly associated different single nucleotide polymorphisms (SNPs) with AF. One of these GWAS identified the rs13376333 risk SNP as the most significant one from the 1q21 chromosomal region. The rs13376333 risk SNP is intronic to the KCNN3 gene that encodes for small conductance calcium-activated potassium channels type 3 (SK3). However, the functional electrophysiological effects of this variant are not known. SK channels represent a unique family of K+ channels, primarily regulated by cytosolic Ca2+ concentration, and different studies support their critical role in the regulation of atrial excitability and consequently in the development of arrhythmias like AF. Since different studies have shown that both upregulation and downregulation of SK3 channels can lead to arrhythmias by different mechanisms, an important goal is to elucidate whether the rs13376333 risk SNP is a gain-of-function (GoF) or a loss-of-function (LoF) variant. A better understanding of the functional consequences associated with these SNPs could influence clinical practice guidelines by improving genotype-based risk stratification and personalized treatment. Although research using native human atrial cardiomyocytes and animal models has provided useful insights, each model has its limitations. Therefore, there is a critical need to develop a human-derived model that represents human physiology more accurately than existing animal models. In this context, research with human induced pluripotent stem cells (hiPSC) and subsequent generation of cardiomyocytes derived from hiPSC (hiPSC-CMs) has revealed the underlying causes of various cardiovascular diseases and identified treatment opportunities that were not possible using in vitro or in vivo studies with animal models. Thus, the ability to generate atrial cardiomyocytes and atrial tissue derived from hiPSCs from human/patients with specific genetic diseases, incorporating novel genetic editing tools to generate isogenic controls and organelle-specific reporters, and 3D bioprinting of atrial tissue could be essential to study AF pathophysiological mechanisms. In this review, we will first give an overview of SK-channel function, its role in atrial fibrillation and outline pathophysiological mechanisms of KCNN3 risk SNPs. We will then highlight the advantages of using the hiPSC-CM model to investigate SNPs associated with AF, while addressing limitations and best practices for rigorous hiPSC studies.

Atrial fibrillation (AF) is a prevalent multifactorial arrhythmia associated with specific single-nucleotide polymorphisms (SNPs). Pulmonary vein (PV) isolation is an established treatment for AF; however, recurrence risk remains caused by AF triggers beyond the PVs. Understanding the embryological origins of these triggers could improve treatment outcomes. This study aimed to investigate the association between embryologically categorized AF triggers, clinical and genetic backgrounds, and postablation prognosis. In cohort 1, comprising 3,067 patients with AF undergoing PV isolation, the clinical characteristics and outcomes were analyzed. Among them, 815 patients underwent genetic analysis using AF-associated SNPs (cohort 2). Patients were delineated based on the developmental origin of the AF triggers: common PV, sinus venosus (SV), and primitive atrium (PA). SV-origin extra-PV AF triggers occurred in 20.3% (n = 622) of patients, whereas PA-origin triggers occurred in 11.9% (n = 365) of patients in cohort 1. Multivariate analysis of cohort 2 revealed that female sex, lower body mass index, absence of hypertension, rs2634073 near PITX2 , and rs6584555 in NEURL1 were associated with SV-AF, whereas nonparoxysmal AF and rs2634073 near PITX2 were predictors of PA-AF. The PA group had a significantly higher arrhythmia recurrence rate after repeated procedures than the common PV (HR: 1.75; 95% CI: 1.34-2.29; P < 0.001) and SV-AF (HR: 1.31; 95% CI: 1.19-1.45; P < 0.001) groups with more de novo AF triggers. However, the incidence of adverse events did not differ significantly among the 3 groups. SV-derived AF triggers may have hereditary factors with a favorable postablation prognosis, whereas PA-derived triggers are linked to AF persistence and poor ablation response. Variants near PITX2 may play a pivotal role in extra-PV triggers. [Display omitted] [ABSTRACT FROM AUTHOR]

Risk stratification in Brugada syndrome (BrS) is based on the occurrence of dynamic factors, such as unexplained syncope and documentation of spontaneous type 1 pattern. At odds with other channelopathies, the role of nonmodifiable risk factors such as sex or genetics remains uncertain. This study aims to identify nonmodifiable risk factors for the occurrence of life-threatening arrhythmic events (LAEs) and define their clinical utility. Clinical and genetic data from consecutive, unrelated Italian patients with Brugada syndrome screened on the sodium voltage-gated channel alpha subunit 5 (SCN5A) gene and 3 pivotal single-nucleotide variations (formerly single-nucleotide polymorphisms) associated with BrS (rs11708996, rs10428132, and rs9388451) were analyzed using multivariable Cox proportional hazards model. In 2,182 unrelated patients with BrS (81% males; median age at diagnosis: 41.6 years [Q1-Q3: 33.4-50.3 years]), male sex (HR: 3.6; 95% CI: 1.9-6.9; P = 0.0001), missense SCN5A mutations in BrS-enriched domains (HR: 2.3; 95% CI: 1.2-4.3; P = 0.008), nonmissense SCN5A mutations (HR: 3.2; 95% CI: 1.8-5.7; P < 0.001), and polygenic risk score for BrS (HR: 1.3; 95% CI: 1.0-1.6; P = 0.041) were all independently associated with a significantly higher risk of a first LAE since birth. Based on these results, we derived the nonmodifiable risk of each patient with BrS, and the division of nonmodifiable risk into tertiles identified 3 distinct risk profiles. In an analysis at follow-up, nonmodifiable risk was independently associated with LAE at follow-up (HR: 1.8; 95% CI: 1.1-2.7; P = 0.014), alongside classical predictors including: history of LAE before diagnosis (HR: 13.8; 95% CI: 8.1-23.7; P < 0.0001), history of unexplained syncope before diagnosis (HR: 4.1; 95% CI: 2.4-6.8; P < 0.0001), and spontaneous type 1 pattern at diagnosis (HR: 2.1; 95% CI: 1.2-3.8; P = 0.010). The model was internally validated, and we derived the equation permitting to calculate the granular 5-year risk of experiencing an LAE at follow-up for each patient with BrS, which may be used to facilitate clinical decision-making. Our data show that male sex, type of SCN5A mutation, and polygenic risk score for BrS define the nonmodifiable risk of each patient with BrS. Nonmodifiable risk is independently associated with LAE, regardless of symptoms or pattern type. [ABSTRACT FROM AUTHOR]

Objective: Single nucleotide polymorphisms (SNPs) are linked to carcinogenesis. Pathogenic variants in the CDH1 gene are associated with gastric cancer. This study examines the genotype and allele frequencies of three SNPs (rs16260, rs13689, and rs9929218) in the CDH1 gene and their relationship with gastric cancer risk. Materials and methods: The study involved 105 gastric cancer patients with pathology results and 105 healthy controls. Clinical, histopathological, and demographic data were collected and compared between the two groups. Results: No significant differences were found for rs16260 (− 160 C > A) and rs9929218 (G > A) between patients and controls (p > 0.05). For rs13689 (T > C), the T allele frequency was 90% in patients versus 69% in controls, while the C allele frequency was 10% in patients versus 31% in controls. A significant difference was observed for this SNP, with a higher T allele frequency in patients (OR = 4.03 CI95% 2.4–6.7, p < 0.0001) compared with controls, suggesting a fourfold increased risk of gastric cancer. Genotype frequencies were 80% wild-type (TT) and 20% heterozygous-type (TC) in patients, and 58% TT, 22% TC, and 20% mutant-type (CC) in controls (p < 0.0001). The frequencies of non-C allele carriers (TT) were present in 80% of patients versus 58.1% of controls (OR = 2.88 CI95% 1.56–5.34, p = 0.0006). Conclusion: This study is the first to link the rs13689 SNP's T allele and TT genotype with increased gastric cancer risk. Our results suggest that the rs13689 T allele may contribute significantly to disease susceptibility, while the rs16260 CC genotype and rs9929218 GG genotype may influence risk in smokers. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Recent shifts in consumer dietary preferences have led to a significant decline in rice consumption in Korea, resulting in surplus rice production. To address this issue, rice flour has been proposed as a substitute for wheat flour. However, the physical, chemical and structural differences between rice and wheat, particularly in grain hardness, pose challenges in using rice flour as an alternative. Understanding the genetic factors that influence rice grain hardness is crucial for improving the milling process and producing high‐quality rice flour suitable for wheat flour substitution.In this study, various grain traits, including length, width, thickness, length‐to‐width ratio and hardness, were measured in a population of brown and milled rice. Quantitative trait locus (QTL) analysis revealed a significant association between grain hardness and thickness, with QTLs for grain hardness mapped on chromosomes 1 and 12 for brown and milled rice, respectively. A total of 20 candidate genes related to grain hardness were identified through QTL analysis. Among them, OsFLOq12 (LOC_Os12g43550) was identified as a key gene influencing grain hardness, which encodes a Ras small GTPase. Phenotypic analysis showed differences in endosperm appearance and particle size between lines with low and high grain hardness.The genetic analysis of OsFLOq12 revealed a single nucleotide polymorphism associated with grain hardness. This study provides valuable insights into the genetic background of grain hardness, offering a foundation for breeding rice varieties optimized for flour production as a viable substitute for wheat flour. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Although patterns of population genomic variation are well‐studied in animals, there remains room for studies that focus on non‐model taxa with unique biologies. Here we characterise and attempt to explain such patterns in mygalomorph spiders, which are generally sedentary, often occur as spatially clustered demes and show remarkable longevity. Genome‐wide single nucleotide polymorphism (SNP) data were collected for 500 individuals across a phylogenetically representative sample of taxa. We inferred genetic populations within focal taxa using a phylogenetically informed clustering approach, and characterised patterns of diversity and differentiation within‐ and among these genetic populations, respectively. Using phylogenetic comparative methods we asked whether geographical range sizes and ecomorphological variables (behavioural niche and body size) significantly explain patterns of diversity and differentiation. Specifically, we predicted higher genetic diversity in genetic populations with larger geographical ranges, and in small‐bodied taxa. We also predicted greater genetic differentiation in small‐bodied taxa, and in burrowing taxa. We recovered several significant predictors of genetic diversity, but not genetic differentiation. However, we found generally high differentiation across genetic populations for all focal taxa, and a consistent signal for isolation‐by‐distance irrespective of behavioural niche or body size. We hypothesise that high population genetic structuring, likely reflecting combined dispersal limitation and microhabitat specificity, is a shared trait for all mygalomorphs. Few studies have found ubiquitous genetic structuring for an entire ancient and species‐rich animal clade. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal symptoms are now detected early in the clinical course of many dementia patients, and studies of the microbiome-gut-brain axis have confirmed bidirectional interactions between the gut and the brain. However, the causal relationship between gut microbiota and cognitive impairment has not been fully established. Therefore, this study conducted a bidirectional Mendelian randomization study to elucidate the potential causal relationship of gut microbiota to cognitive impairment. Objective: Using Mendelian randomization to identify gut flora with a genetic causal effect on the development of cognitive impairment. Methods: This study utilized publicly available genome-wide association study summary data to perform MR analysis, with gut microbiota as the exposure and various cognitive function indicators as well as scores for Alzheimer's disease as outcomes. This study selected single nucleotide polymorphisms as instrumental variables based on p-values, F-statistics, and r2. Bidirectional Mendelian randomization was conducted using methods such as inverse variance weighted, MR-Egger, simple mode, and weighted mode to assess the causal relationship. Concurrently, this study carried out Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis to identify potential heterogeneity and horizontal pleiotropy. Results: This study identified a total of 31 gut microbes that have a causal relationship with cognitive impairment, which include 1 phylum, 4 classes, 3 orders, 2 families, and 21 genera. Conclusions: This study unveiled specific gut microbiota associated with cognitive impairment, offering new insights and approaches for the prevention and treatment of cognitive impairment through gut microbiota such as Bifidobacterium and Ruminococcus gnavus group. [ABSTRACT FROM AUTHOR]

Background: Genetic variations in a common single nucleotide polymorphism in the ninth intron of the KIBRA gene have been linked to memory performance and risk of Alzheimer's disease (AD). Objective: We examined the risk of AD related to presence of KIBRA T allele (versus CC homozygote) and to memory performance. The role of established genetic risk factors APOE ε4 and BDNF Met was also considered. Methods: Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory. Results: KIBRA T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, p = 0.012) compared to KIBRA CC genotype. In APOE ε4 negative individuals, KIBRA T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, p = 0.038) and AD dementia (OR = 15.75, p = 0.009). In BDNF Met positive individuals, the KIBRA T allele was associated with a greater risk of AD dementia (OR = 10.98, p = 0.050). In AD dementia, the association between KIBRA T allele and better memory performance approached significance (β = 0.42; p = 0.062). The link between possessing the KIBRA T allele and better memory reached statistical significance only among BDNF Met carriers (β = 1.21, p = 0.027). Conclusions: Findings suggest that KIBRA T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits. [ABSTRACT FROM AUTHOR]

Rs768705 (TMEM161B) is one of the identified single nucleotide polymorphisms related to major depressive disorder (MDD). Paranoid personality traits are independently associated with the risk of MDD. This study aimed to investigate the interaction effect between rs768705 (TMEM161B) and paranoid personality traits on the new-onset risk of MDD in Chinese freshmen. A longitudinal study was conducted among 7642 Chinese freshmen without lifetime MDD at baseline in 2018. 158 new-onset MDD cases were ascertained in 2019. DNA samples were extracted to detect the genotype of rs768705. The diagnostic and statistical manual of mental disorders-IV criteria were used to determine MDD and personality disorder traits. Multiplicative interaction was assessed by logistic regression models. Tomas Andersson's method for calculating biological interactions was used to estimate the additive interaction. Rs768705(AG) (OR = 1.88, 95 % CI: 1.24–2.83) and paranoid personality traits (OR = 3.68, 95 % CI: 2.57–5.26) were significantly associated with the risk of MDD. The multiplicative interaction model with the product term of rs768705 and paranoid personality trait traits had a significant interaction effect (OR = 4.20, 95 % CI:1.62–10.91). There was also a significant additive interaction effect (RR = 7.08, 95 % CI:4.31–11.65) for the incidence of MDD. Seventy seven percent patients among new MDD cases were attributed to the additive interaction effect between rs768705 and paranoid personality traits. Rs768705 (AG) may interact with paranoid personality traits to increase the incidence of MDD among Chinese college students. Schools and psychosocial health organizations should pay more attention to individuals with paranoid personality traits for MDD intervention and prevention. • This was a 1-year longitudinal study conducted among 7642 Chinese freshmen. • There was an addictive interaction effect between rs768705 (AG) and paranoid personality traits on occurrence of MDD. • 77% of new MDD patients were attributed to the interaction effect of rs768705 (AG) & paranoid personality traits. [ABSTRACT FROM AUTHOR]

Reversing cancer cachexia remains a challenge. Genetic biomarkers for the early detection of the disease have been explored in order to enable the implementation of preventive measures. We therefore genotyped candidate genes based on cachexia phenotype and quantified adiponectin and GDF-15 levels in cachectic patients with gastrointestinal cancer. Patients with a diagnosis of gastrointestinal cancer were divided into a cachectic and a non-cachectic group after the start of chemotherapy. A control group (no cancer) was also included. We genotyped the following single nucleotide polymorphisms (SNPs) by quantitative PCR: FOXO3 (rs1935949), FOXO3 (rs4946935), ACVR2B (rs2268757), and SELP (rs6136). In addition, we quantified adiponectin and GDF-15 levels by ELISA. The rs2268757 SNP in the ACVR2B gene was associated with the weight loss phenotype in cachectic patients with gastrointestinal cancer (non-cachectic, P = 0.004). Plasma adiponectin levels were higher in cachectic patients compared to controls (P = 0.01) and non-cachectic patients (P = 0.004). GDF-15 was also elevated in cachectic patients compared to controls (P < 0.0001) and non-cachectic patients (P = 0.001). Analysis by sex showed elevated adiponectin levels in men (control, P = 0.01) and cachectic women (control, P = 0.04; non-cachectic, P = 0.01), as well as elevated GDF-15 levels in men (control, P = 0.002) and cachectic women (control, P = 0.002; non-cachectic, P = 0.007). However, there was no significant difference in the levels of these cytokines between cachectic men and women. The results suggest the rs2268757 SNP in the ACVR2B gene, adiponectin, and GDF-15 as potential biomarkers of cachexia in gastrointestinal cancer. [ABSTRACT FROM AUTHOR]

Potassium ion channels play a fundamental role in regulating cell membrane repolarization, modulating the frequency and shape of action potentials, and maintaining the resting membrane potential. A growing number of studies have indicated that dysfunction in potassium channels associates with the pathogenesis and treatment of depression. However, the involvement of potassium channels in the onset and treatment of depression has not been thoroughly summarized. In this review, we performed a comprehensive analysis of the association between multiple potassium channels and their roles in depression, and compiles the SNP loci of potassium channels associated with depression, as well as antidepressant drugs that target these channels. We discussed the pivotal role of potassium channels in the treatment of depression, provide valuable insights into new therapeutic targets for antidepressant treatment and critical clues to future drug discovery. [ABSTRACT FROM AUTHOR]

Background: Although caffeine (CAF) supplementation has been shown to improve exercise performance, its dose-dependent effect on CAF metabolism has not been sufficiently investigated. The aim of this study was to evaluate the effects of 3, 6 and 9 mg of CAF/kgBM on changes of CAF and paraxanthine (PRX) in the serum and saliva at four time-points. Methods: In a randomized, double-blind, placebo-controlled crossover design, acute pre-exercise supplementation in 26 moderately-trained athletes, participating in high-intensity functional training (HIFT), was examined. The study protocol involved CAF/PRX biochemical analyses of serum and saliva with respect to CYP1A2 polymorphism and CYP1A2 enzyme activity. Results: Despite significant differences between the serum and saliva levels of CAF and PRX, there was no difference in the PRX/CAF ratio. The interaction effect of dose and time-points for PRX concentration was revealed. The main effects of dose were observed for CAF and the PRX/CAF ratio. The main effect of time-points was registered only for serum CAF. Conclusions: Dose- and time-dependent effect of CAF supplementation on CAF and PRX in the serum and saliva of athletes was confirmed, but there was no effect of the CAF dose on CYP1A2 enzyme activity, nor was there an interaction of CYP1A2 with enzyme inducibility. The CAF/PRX correlation indicated the possibility of interchangeable use of serum and/or saliva analyses in exercise studies. Clinical trial registration: This trial was registered prospectively at ClinicalTrials.gov (NCT03822663, registration date: 30/01/2019). [ABSTRACT FROM AUTHOR]

Stripes and bands are common colour patterns in snakes. Some species are known to exhibit colour polymorphism and that includes expressing it in the bands and stripes. Bridal snake, Dryocalamus is a medium‐sized arboreal snake in South to Southeast Asia and most species of the genus are banded, but including two striped species. In Borneo, banded D. subannulatus and striped D. tristrigatus occur sympatrically and the two species are similar morphologically except for their colour patterns. We hypothesized the two species in Borneo exhibit a significant colour dimorphism of one species and conducted morphological and genetical analysis to test the hypothesis. Morphological examinations revealed that D. subannulatus and D. tristrigatus are not distinguishable in Borneo by scalation. Mitochondrial phylogenetic analysis and nuclear SNP analysis showed D. subannulatus and D. tristrigatus from Borneo formed clades or clusters by region not by species. Dryocalamus subannulatus and D. tristrigatus in Borneo are morphologically and genetically indistinguishable and Bornean D. subannulatus should be treated as a colour morph of D. tristrigatus. This is a rare example of sympatrically distinct banded/striped dimorphism in snakes. Relative abundance of banded/striped morph of the genus is probably different depending on region, and any ecological factor may contribute to it. [ABSTRACT FROM AUTHOR]

The Sardo Negro cattle (SN) is the only zebu cattle breed developed in Mexico. Since its development, the selection could have led to an increase in the homozygosity level in some regions of the genome and made differentiation with other cattle populations. We aimed to identify and characterize selection signatures in SN using medium-density SNP data using four approaches: 1) Runs of homozygosity (ROH) 2) Nucleotide Diversity 3) Tajima's D and 4) the Wright's fixation index (FST). A sample of 555 SN animals genotyped for 65k SNPs was used to obtain ROH segments considered regions under selection. The FST values were estimated by comparing the sample of genotyped SN animals with samples of genotyped animals from the Gir, Brahman, and Ongole breeds. Only one region mapped to 35.78–42.51 Mb on BTA6 was considered a selection signature by the ROH method. This selection signature overlapped with the lowest diversity, negative values of Tajima's D and a diversification region between SN and the other Zebu breeds by FST. We found several candidate genes (LCORL, NCAPG, and SLIT2) related to growth and other economically important productive traits in this common region. Using the FST method, different regions, such as regions on BTA8 (8:93.4–93.9 Mb), BTA11 (11:99.2–99.7), and BTA14 (14: 26.1–26.8) related to growth and milk traits also were defined as candidate selection signatures. The selective signals identified in this study reflected the direction of the selection pressure that primarily involves the increase of live weight traits in the Sardo Negro cattle breeding program. [ABSTRACT FROM AUTHOR]

Premise Methods Results Discussion Leveraging DNA markers, particularly single‐nucleotide polymorphisms (SNPs), in parentage analysis, sib‐ship reconstruction, and genomic relatedness analysis can enhance plant breeding efficiency. However, the limited availability of genomic information, confined to the most commonly used species, hinders the broader application of SNPs in species of lower economic interest (e.g., most tree species). We explored the possibility of using universal target capture probes, namely Angiosperms353, to identify SNPs and assess their effectiveness in genomic relatedness analysis.We tested the approach in 11 tree species, six of which had a half‐sib family structure. Variants were called within species, and genomic relatedness analysis was conducted in species with two or more families. Scalability via amplicon sequencing was tested by designing primers and testing them in silico.Adequate SNPs for relatedness analysis were identified in all species. Relatedness values from Angiosperms353‐based SNPs highly correlated with those from thousands of genome‐wide DArTseq SNPs in Cordia africana, one of the species with a family structure. The in silico performance of designed primers demonstrated the potential for scaling up via amplicon sequencing.Utilizing universal target capture probes for SNP identification can help overcome the limitations of genomic information availability, thereby enhancing the application of genomic markers in breeding plant species with lower economic interest. [ABSTRACT FROM AUTHOR]

Background: Despite the growing number of studies investigating the connection between host genetics and the rumen microbiota, there remains a dearth of systematic research exploring the composition, function, and metabolic traits of highly heritable rumen microbiota influenced by host genetics. Furthermore, the impact of these highly heritable subsets on lactation performance in cows remains unknown. To address this gap, we collected and analyzed whole-genome resequencing data, rumen metagenomes, rumen metabolomes and short-chain fatty acids (SCFAs) content, and lactation performance phenotypes from a cohort of 304 dairy cows. Results: The results indicated that the proportions of highly heritable subsets (h2 ≥ 0.2) of the rumen microbial composition (55%), function (39% KEGG and 28% CAZy), and metabolites (18%) decreased sequentially. Moreover, the highly heritable microbes can increase energy-corrected milk (ECM) production by reducing the rumen acetate/propionate ratio, according to the structural equation model (SEM) analysis (CFI = 0.898). Furthermore, the highly heritable enzymes involved in the SCFA synthesis metabolic pathway can promote the synthesis of propionate and inhibit the acetate synthesis. Next, the same significant SNP variants were used to integrate information from genome-wide association studies (GWASs), microbiome-GWASs, metabolome-GWASs, and microbiome-wide association studies (mWASs). The identified single nucleotide polymorphisms (SNPs) of rs43470227 and rs43472732 on SLC30A9 (Zn2+ transport) (P < 0.05/nSNPs) can affect the abundance of rumen microbes such as Prevotella_sp., Prevotella_sp._E15-22, Prevotella_sp._E13-27, which have the oligosaccharide-degradation enzymes genes, including the GH10, GH13, GH43, GH95, and GH115 families. The identified SNPs of chr25:11,177 on 5s_rRNA (small ribosomal RNA) (P < 0.05/nSNPs) were linked to ECM, the abundance alteration of Pseudobutyrivibrio_sp. (a genus that was also showed to be linked to the ECM production via the mWASs analysis), GH24 (lysozyme), and 9,10,13-TriHOME (linoleic acid metabolism). Moreover, ECM, and the abundances of Pseudobutyrivibrio sp., GH24, and 9,10,13-TRIHOME were significantly greater in the GG genotype than in the AG genotype at chr25:11,177 (P < 0.05). By further the SEM analysis, GH24 was positively correlated with Pseudobutyrivibrio sp., which was positively correlated with 9,10,13-triHOME and subsequently positively correlated with ECM (CFI = 0.942). Conclusion: Our comprehensive study revealed the distinct heritability patterns of rumen microbial composition, function, and metabolism. Additionally, we shed light on the influence of host SNP variants on the rumen microbes with carbohydrate metabolism and their subsequent effects on lactation performance. Collectively, these findings offer compelling evidence for the host-microbe interactions, wherein cows actively modulate their rumen microbiota through SNP variants to regulate their own lactation performance. C1VA69ck9huqCRa2wNrTKW Video Abstract [ABSTRACT FROM AUTHOR]

The study published in the Blood Cancer Journal explores the relationship between genetically determined telomere length (gdLTL) and the risk of developing monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Using single nucleotide polymorphisms (SNPs) as proxies for measuring gdLTL, the study found that longer gdLTL was associated with an increased risk of developing MM. Additionally, the study observed a significant association between longer gdLTL and improved survival in MM patients. The findings suggest that gdLTL may serve as a marker for MM risk and potentially influence the development of pre-malignant conditions like MGUS. [Extracted from the article]

Genomic Selection (GS) in tree breeding optimizes genetic gains by leveraging genomic data to enable early selection of seedlings without phenotypic data reducing breeding cycle and increasing selection intensity. Traditional assessments of the potential of GS in forest trees have typically focused on model performance using cross-validation within the same generation but evaluating effectively realized predictive ability (RPA) across generations is crucial. This study estimated RPAs for volume growth (VOL), wood density (WD), and pulp yield (PY) across four generations breeding of Eucalyptus grandis. The training set spanned three generations, including 34,461 trees with three-year growth data, 6,014 trees with wood quality trait data, and 1,918 trees with 12,695 SNPs (single nucleotide polymorphisms) data. Employing single-step genomic BLUP, we compared the genomic predictions of breeding values (GEBVs) for 1,153 fourth-generation full-sib seedlings in the greenhouse with their later-collected phenotypic estimated breeding values (EBVs) at age three years. RPAs were estimated using three GS targets (individual trees, trees within families, and families), two selection criteria (single- and multiple-trait), and training populations of either all 1,918 genotyped trees or the 67 direct ancestors of the selection candidates. RPAs were higher for wood quality traits (0.33 to 0.59) compared to VOL (0.14 to 0.19) and improved for wood traits (0.42 to 0.75) but not for VOL when trained only with direct ancestors, highlighting the challenges in accurately predicting growth traits. GS was more effective at excluding bottom-ranked candidates than selecting top-ranked ones. The between-family GS approach outperformed individual-tree selection for VOL (0.11 to 0.16) and PY (0.72 to 0.75), but not for WD (0.43 vs. 0.42). Furthermore, higher levels of relatedness and lower genotype by environment (G × E) interaction between training and testing populations enhanced RPAs for VOL (0.39). In summary, despite limited effectiveness in ranking top VOL individuals, GS effectively identified low-performing individuals and families. These multi-generational findings underscore GS's potential in tree breeding, stressing the importance of considering relatedness and G × E interaction for optimal performance. [ABSTRACT FROM AUTHOR]

Pepper (Capsicum spp.) is one of the most important crops worldwide. Understanding the species' genetic background is key to preserve agrodiversity on-farm, to contribute to a more diverse and resilient agrifood sector, and to find new sources of variation that could be useful in future breeding programs. In this regard, varietal groups bred in insular environments have gained special interest as they have evolved quite isolated from continental forms, with a limited genetic exchange. The present work explores the diversity of a plethora of Balearic landraces, corresponding to different local varietal types, through phenotyping and genotyping-by-sequencing (GBS). Mallorca and Eivissa landraces were phenotyped according to a comprehensive list of descriptors for plant, leaf, flower, fruit, pollen, and seed and were genotyped with single nucleotide polymorphism (SNP) markers; population structure and their patterns of diversity were studied. The results showed a considerable morphological diversity for most traits analyzed, within and between landraces. On the whole, in regard to genetic patterns, relatively low levels of heterozygosity and moderate genetic diversity for the studied landraces were found although some of them exhibited diverse patterns. The materials were not grouped in specific clusters associated with each island, but mainly according to varietal types. These findings can serve as the basis for studying divergent evolutionary patterns associated with the corresponding populations. Finally, the results can contribute to further elucidation of the genetic basis of Balearic landraces and serve as an inspiring case of study for other insular endemisms of cultivated species. [ABSTRACT FROM AUTHOR]

Introduction: Human brucellosis is a severe public concern in Shaanxi Province, China, and investigating the epidemiological relationship and transmission pattern of B. melitensis is necessary to devise control strategies. Methods: In this study, a conventional bio-typing approach and whole genome sequencing of single-nucleotide polymorphisms (SNPs) were employed to identify 189 strains. Results: Based on the conventional bio-typing, 189 Brucella strains were identified as B. melitensis , of which 14 were in bv. 1, 145 were in bv. 3, and 30 were variant, and the Brucella strains were distributed in all ten cities in Shaanxi Province. SNP analysis was used to identify genetic variation in 189 B. melitensis genomes, and maximum-likelihood was used to generate a phylogeny that identified two clades (A and B) and 19 sequence types (STs). The two clades were highly diverse and exclusively of Eastern Mediterranean origin. Clade B contained 18 STs (2-19), with most isolates originating from a broad swath, implying that multiple B. melitensis lineages circulated in Shaanxi. The 19 STs were composed of 3 to 46 strains isolated from different counties and years, suggesting that multiple cross-county brucellosis outbreak events are driven by multiple B. melitensis lineages. Global phylogenetic analysis revealed that clade A was close to GTIIb, and clade B was placed in the GTIIh lineage, expanding the known diversity of B. melitensis from China. Conclusion: The human brucellosis epidemic in Shaanxi is driven by multiple indigenous circulating B. melitensis lineages, the knowledge of which will contribute to devising a control strategy and providing the foundation for a comprehensive regional phylogeny of this important zoonotic pathogen. [ABSTRACT FROM AUTHOR]

Background: Many clinical variables might impact the pharmacokinetics of calcineurin inhibitors (CIs). Different alleles of cytochromes P450 (CYP)3A4/5 and drug transporter P-glycoprotein are the main variables. Other variables include relocated type, treatment duration after transplantation, age, sex, dietary consumption, medications used and renal or hepatic impairment. Tacrolimus and cyclosporine are two main CIs extensively used in organ transplantation. Both drugs are metabolized by CYP3A4 and CYP3A5 isoforms, and single-nucleotide polymorphisms in these genes have been displayed to influence CIs pharmacokinetics. Another important gene is the pregnane X receptor (PXR), which manages the statement of a variety of genes including CYP3A4 genes. PXR has a clinical significance in CIs metabolism. The liver is the essential site for CIs metabolism. A decreased clearance with a prolonged CIs half-life was occurred in patients with impaired liver compared with patients with normal liver function. The presence of different genetic and clinical factors that may affect calcineurin inhibitors trough levels will consequently affect their immunosuppressant effect after liver transplantation. Purpose: This study aims to determine the effect of different genetic polymorphisms in CYP3A4 1B rs2740574 and PXR A7635G rs6785049 and other clinical factors that may affect calcineurin inhibitors pharmacokinetics after liver transplantation. Results: The presence of T allele in CYP3A4 gene was associated with elevated DATLs with P values of 0.00, 0.00, 0.007 and 0.00 after tacrolimus doses 4, 30, 60 and 90, respectively. Regarding PXR gene, the presence of G allele was associated with elevated DATLs in cyclosporine. About 432 correlations were tested in both drugs. In CYP3A4 genotype CC, male sex was associated with elevated DATLs interpreted by strong positive correlations and statistically significant difference in all DATLs, except DATL 60 (P value 0.374). No strong association was found between low hemoglobin levels and DATLs in almost all the follow-up periods. There were many positive relations between increased total and direct bilirubin and increased DATLs. Conclusions: Studying the various genetics and clinical factors that may affect calcineurin inhibitors serum concentrations is very essential for successful treatment plans after organ transplantation. These different factors may interact with each other and these complicated interactions may complicate the patient's conditions post-transplantation. Considering all these complicated interactions is very crucial in monitoring treatment plans, especially in the presence of other comorbidities or chronic diseases. More studies with large number of patients should be conducted to explore more consequences of these interacting variables of treatment plans of these patients and all studied parameters in this study should be considered while monitoring patients after transplantation. [ABSTRACT FROM AUTHOR]

Understanding the genetic diversity of crops is of fundamental importance for the efficient use and improvement of germplasm resources. Different molecular genotyping systems have been implemented for population structure and phylogenetic relationships analyses, among which, microsatellites (SSRs) and single nucleotide polymorphisms (SNPs) markers have been the most widely used. This study reports the efficacy of SNPs detected via double-digest restriction-site-associated DNA sequencing (ddRADseq) and SSRs analyzed via capillary electrophoresis (CE) and high-resolution melting (HRM) in tomato. In total, 21,020 high-quality SNPs, 20 CE-SSRs, and 17 HRM-SSR markers were assayed in a panel of 72 accessions that included a diversified set of landraces, long-shelf-life cultivars and heirlooms with different origins and fruit typology. The results showed how the population structure analysis was consistent using the three genotyping methods, although SNPs were more efficient in distinguishing cultivar types and in measuring the degree of accessions' similarity. Compared to CE-SSR, the analysis of microsatellites via HRM yielded a slightly higher number of alleles (98 vs. 96). HRM-SSR demonstrated a distinction between European and non-European germplasm, better resolving the collection's diversity and being more consistent with SNP data. Phylogenetic trees drawn with independent marker data, detected specific groups of accessions showing robust clusters, highlighting how heirlooms were less heterogeneous than landraces. In addition, the fixation index (FST) revealed a high genetic differentiation between heirlooms and long-shelf-life cultivars, with SNP and SSR-HRM data emphasizing the distinction between cherry and plum types and CE-SSR data between cherry and oxheart types. In all instances, a greater molecular variance was found within the different considered biological statuses, provenances, and typologies rather than among them. This work presents the first attempt to compare the three tomato genotyping techniques in tomato. Findings highlighted how the markers used are complementary for genetic diversity analysis, with SNPs providing better insight and HRM-SSR as a viable alternative to capillary electrophoresis to dissect the genetic structure. [ABSTRACT FROM AUTHOR]

Background: Interferon-induced helicase C domain-containing protein 1 (IFIH1) is one of the main pattern recognition receptors that sense viral RNA and activate host cells to mount an effective antiviral immunity. Methods: A case–control study (90 patients with mild/moderate COVID-19 and 90 matched controls) was performed to explore the association of two variants of the IFIH1 gene with COVID-19 risk using the tetra-primer amplification refractory mutation system-polymerase-chain-reaction method. The first is a missense variant, rs1990760 C/T, and the second is an intergenic variant, rs2111485 A/G. In addition, serum IFIH1 levels were assessed using an ELISA kit. Results: Mutant alleles (T and G, respectively) and corresponding homozygous genotypes (TT and GG, respectively) of both variants were significantly associated with increased risk of COVID-19. IFIH1 levels were significantly higher in patients compared to controls and were favorably affected by the rs1990760 and rs2111485 mutant-type genotypes. Conclusion: IFIH1 protein showed up-regulated levels in the serum of patients with mild/moderate COVID-19. In addition, the IFIH1 gene variants rs1990760 C/T and rs2111485 A/G were associated with susceptibility to COVID-19, and the study suggests that their mutant-type genotypes are not only associated with increased risk of COVID-19 but also contributed to higher serum IFIH1 levels. [ABSTRACT FROM AUTHOR]

Tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb), is a major global public health problem, resulting in > 1 million deaths each year. Drug resistance (DR), including the multi-drug form (MDR-TB), is challenging control of the disease. Whilst many DR mutations in the Mtb genome are known, analysis of large datasets generated using whole genome sequencing (WGS) platforms can reveal new variants through the assessment of genotype-phenotype associations. Here, we apply tree-based ensemble methods to a dataset comprised of 35,777 Mtb WGS and phenotypic drug-susceptibility test data across first- and second-line drugs. We compare model performance across models trained using mutations in drug-specific regions and genome-wide variants, and find high predictive ability for both first-line (area under ROC curve (AUC); range 88.3–96.5) and second-line (AUC range 84.1–95.4) drugs. To aggregate information from low-frequency variants, we pool mutations by functional impact and observe large improvements in predictive accuracy (e.g., sensitivity: pyrazinamide + 25%; ethionamide + 10%). We further characterise loss-of-function mutations observed in resistant phenotypes, uncovering putative markers of resistance (e.g., ndh 293dupG, Rv3861 78delC). Finally, we profile the distribution of known DR-associated single nucleotide polymorphisms across discretised minimum inhibitory concentration (MIC) data generated from phenotypic testing (n = 12,066), and identify mutations associated with highly resistant phenotypes (e.g., inhA − 779G > T and 62T > C). Overall, our work demonstrates that applying machine learning to large-scale WGS data is useful for providing insights into predicting Mtb binary drug resistance and MIC phenotypes, thereby potentially assisting diagnosis and treatment decision-making for infection control. [ABSTRACT FROM AUTHOR]

CRISPR/Cas12a is a highly promising detection tool. However, detecting single nucleotide variations (SNVs) remains challenging. Here, we elucidate Cas12a specificity through crRNA engineering and profiling of single- and double-base mismatch tolerance across three targets. Our findings indicate that Cas12a specificity depends on the number, type, location, and distance of mismatches within the R-loop. We also find that introducing a wobble base pair at position 14 of the R-loop does not affect the free energy change when the spacer length is truncated to 17 bp. Therefore, we develop a new universal specificity enhancement strategy via iterative crRNA design, involving truncated spacers and a wobble base pair at position 14 of the R-loop, which tremendously increases specificity without sacrificing sensitivity. Additionally, we construct a PAM-free one-pot detection platform for SARS-CoV-2 variants, which effectively distinguishes SNV targets across various GC contents. In summary, our work reveals new insights into the specificity mechanism of Cas12a and demonstrates significant potential for in vitro diagnostics. A new ultra-specific enhancement strategy for Cas12a via iterative crRNA design. A PAM-free one-pot detection platform for SARS-CoV-2 variants demonstrates significant potential for in vitro diagnostics. [ABSTRACT FROM AUTHOR]

Whole-genome sequencing studies of parent–offspring trios have provided valuable insights into the potential impact of de novo mutations (DNMs) on human health and disease. However, the molecular mechanisms that drive DNMs are unclear. Studies with multi-child families can provide important insight into the causes of inter-family variability in DNM rates but they are highly limited. We characterized 2479 de novo single nucleotide variants (SNVs) in 13 multi-child families of Mexican-American ethnicity. We observed a strong paternal age effect on validated de novo SNVs with extensive inter-family variability in the yearly rate of increase. Children of older fathers showed more C > T transitions at CpG sites than children from younger fathers. Validated SNVs were examined against one cancer (COSMIC) and two non-cancer (human germline and CRISPR-Cas 9 knockout of human DNA repair genes) mutational signature databases. These analyses suggest that inaccurate DNA mismatch repair during repair initiation and excision processes, along with DNA damage and replication errors, are major sources of human germline de novo SNVs. Our findings provide important information for understanding the potential sources of human germline de novo SNVs and the critical role of DNA mismatch repair in their genesis. Mutational signature analyses of de novo mutations in multi-child human families suggest that inaccurate DNA mismatch repair, DNA damage, and replication errors are major sources of age-related increases in germline mutations. [ABSTRACT FROM AUTHOR]

Objective: Analyze the ultrasound findings, single nucleotide polymorphism array (SNP-array) results, and pregnancy outcomes of fetuses with 7q11.23 deletions and duplications in the second and third trimesters. Investigate the prenatal ultrasound characteristics and follow up information of these fetuses. Methods: Seven fetuses were diagnosed with 7q11.23 deletion and six with 7q11.23 duplication via SNP-array at the prenatal diagnosis center of a single Chinese tertiary medical center from January 2017 to May 2024. Maternal demographics, ultrasound findings, SNP-array results, pregnancy outcomes, and follow-up information were comprehensively reviewed and analyzed. Results: The copy number variations (CNVs) ranged from 1.43 Mb to 1.78 Mb in cases of 7q11.23 deletions and from 1.42 Mb to 1.68 Mb in cases of 7q11.23 duplications. These CNVs encompassed 29 OMIM-listed genes, including ELN, DNAJC30, GTF2IRD1, and GTF2I. Among the seven cases of 7q11.23 deletion syndrome, six exhibited ultrasound abnormalities. The main clinical phenotypes included three cases of intrauterine growth restriction and four cases of cardiovascular system abnormalities, specifically two cases with ventricular septal defects, one case with aortic narrowing, and one case with supravalvular pulmonary stenosis. One case was particularly notable, exhibiting complex multi-organ structural malformations. Out of six cases of 7q11.23 duplication syndrome, five exhibited ultrasound abnormalities. These included two cases of cardiovascular abnormalities: one case with a widened left ventricle and another case with a shortened fetal humerus length. One case revealed complex multi-organ structural malformations, including hydronephrosis, a microgallbladder, and a cleft lip and palate. All seven cases of 7q11.23 deletions and three cases of 7q11.23 duplications opted for termination of the pregnancy. The remaining three cases of 7q11.23 duplications chose to continue the pregnancy. One case underwent surgical treatment for a ventricular septal defect after birth, and the prognosis was favorable. Another case involved a full-term delivery, this child was followed up at the age of 4 and exhibited a phenotype of poor language expression ability. Conclusion: Our study broadened the clinical phenotype spectrum of fetuses with 7q11.23 deletions and duplications. Additionally, it conducted a preliminary evaluation of prenatal ultrasound findings and postnatal clinical phenotypes in follow-up cases. The clinical phenotype of fetuses with 7q11.23 deletion and duplication syndromes involves multiple systems and is relatively complex. Cardiovascular abnormalities and intrauterine growth restriction are the most common clinical manifestations observed in prenatal 7q11.23 deletion syndrome. Fetuses with 7q11.23 duplications exhibit a wide range of clinical phenotypes that lack specificity. [ABSTRACT FROM AUTHOR]

Background: Xinglong buffalo, as an indigenous breed in Hainan province of China, possesses characteristics such as high humidity tolerance, disease resistance and high reproductive capacity. Combined with whole genome sequencing technology, comprehensive investigation can be undertaken to elucidate the genomic characteristics, functions and genetic variation of Xinglong buffalo population. Results: Xinglong buffalo has the highest genetic diversity, lowest runs of homozygosity average length, and fasted decay of linkage disequilibrium in our study population. Phylogenetic tree results revealed that Xinglong buffalo was gathered together with Fuzhong buffalo firstly. The population genetic structure analysis indicates that at K = 3, the Xinglong buffalo for the first time showed a distinct ancestral origin from other water buffalo. Furthermore, compared to different populations, candidate genes displaying significantly distinct patterns of single nucleotide polymorphisms (SNPs) (e.g., RYR2, COX15, PCDH9, DTWD2, FCRL5) distribution have been identified in the Xinglong buffalo. Conclusions: Based on the whole genome sequencing data, this study identified a substantial number of SNPs and assessed the genetic diversity and selection signatures within the Xinglong buffalo population. These results contribute to understanding the genomic characteristics of Xinglong buffalo and their genetic evolutionary status. However, the practical significance of these signatures for genetic enhancement still requires confirmation through additional samples and further experimental validation. [ABSTRACT FROM AUTHOR]

Background: Embryonic genome activation (EGA) is a critical step in early embryonic development, as it marks the transition from relying on maternal factors to the initiation of transcription from embryo's own genome. The factors associated with EGA are not well understood and need further investigation. PRD-like (PRDL) homeodomain transcription factors (TFs) are considered to play crucial roles in this early event during development but these TFs have evolved differently, even within mammalian lineages. Different numbers of PRDL TFs have been predicted in bovine (Bos taurus); however, their divergent evolution requires species-specific confirmation and functional investigations. Results: In this study, we conducted molecular cloning of mRNAs for the PRDL TFs ARGFX, DUXA, LEUTX, NOBOX, TPRX1, TPRX2, and TPRX3 in bovine oocytes or in vitro fertilized (IVF) preimplantation embryos. Our results confirmed the expression of PRDL TF genes in early bovine development at the cDNA level and uncovered their structures. For each investigated PRDL TF gene, we isolated at least one homeodomain-encoding cDNA fragment, indicative of DNA binding and thus potential role in transcriptional regulation in developing bovine embryos. Additionally, our cDNA cloning approach allowed us to reveal breed-related differences in bovine, as evidenced by the identification of a high number of single nucleotide variants (SNVs) across the PRDL class homeobox genes. Subsequently, we observed the prediction of the 9aa transactivation domain (9aaTAD) motif in the putative protein sequence of TPRX3 leading us to conduct functional analysis of this gene. We demonstrated that the TPRX3 overexpression in bovine fibroblast induces not only protein-coding genes but also short noncoding RNAs involved in splicing and RNA editing. We supported this finding by identifying a shared set of genes between our and published bovine early embryo development datasets. Conclusions: Providing full-length cDNA evidence for previously predicted homeobox genes that belong to PRDL class improves the annotation of the bovine genome. Updating the annotation with seven developmentally-important genes will enhance the accuracy of RNAseq analysis with datasets derived from bovine preimplantation embryos. In addition, the absence of TPRX3 in humans highlights the species-specific and TF-specific regulation of biological processes during early embryo development. [ABSTRACT FROM AUTHOR]

Streptococcus suis serotypes 2 and 14 are the most common zoonotic strains, but previous identification methods made distinguish these two serotypes from other S. suis serotypes difficult. To effectively prevent and control them, there is an urgent need for a highly sensitive and specific method to identify these two serotypes. In this study, a fluorescent probe was designed for the single nucleotide polymorphism site at cpsK 483 of Streptococcus suis type 2 and type 14 compared with other serotypes, and an enzyme-activated probe quantitative PCR (EA-probe qPCR) method was established for the detection of Streptococcus suis type 2 and type 14 by combining with the specific hydrolysis characteristics of the RNase H2 enzyme. The results showed that the optimal probe concentration for this method was 0.5 µM and the optimal RNase H2 enzyme concentration was 25 mU.This method showed no reactivity with genomic DNA from Streptococcus suis strains 1/2, 5, 7, 9, 23, 28, 29, and 31, confirming its high specificity. And its sensitivity can reach 18.4 CFU. In addition, 19 clinical strains of Streptococcus suis type 2 or type 1/2 were tested. The results showed 100% agreement with the gene sequencing method. In conclusion, this method can meet the needs of accurate laboratory testing of Streptococcus suis serotypes 2 and 14 and has value for clinical prevention. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are complex, multifactorial conditions that require personalized assessment and treatment. Advancements in multi-omics technologies, namely RNA sequencing and whole-genome sequencing, have provided translational researchers with a comprehensive view of the human genome. The efficient synthesis and analysis of this data through integrated approach that characterizes genetic variants alongside expression patterns linked to emerging phenotypes, can reveal novel biomarkers and enable the segmentation of patient populations based on personalized risk factors. In this study, we present a cutting-edge methodology rooted in the integration of traditional bioinformatics, classical statistics, and multimodal machine learning techniques. Our approach has the potential to uncover the intricate mechanisms underlying CVD, enabling patient-specific risk and response profiling. We sourced transcriptomic expression data and single nucleotide polymorphisms (SNPs) from both CVD patients and healthy controls. By integrating these multi-omics datasets with clinical demographic information, we generated patient-specific profiles. Utilizing a robust feature selection approach, we identified a signature of 27 transcriptomic features and SNPs that are effective predictors of CVD. Differential expression analysis, combined with minimum redundancy maximum relevance feature selection, highlighted biomarkers that explain the disease phenotype. This approach prioritizes both biological relevance and efficiency in machine learning. We employed Combination Annotation Dependent Depletion scores and allele frequencies to identify variants with pathogenic characteristics in CVD patients. Classification models trained on this signature demonstrated high-accuracy predictions for CVD. The best performing of these models was an XGBoost classifier optimized via Bayesian hyperparameter tuning, which was able to correctly classify all patients in our test dataset. Using SHapley Additive exPlanations, we created risk assessments for patients, offering further contextualization of these predictions in a clinical setting. Across the cohort, RPL36AP37 and HBA1 were scored as the most important biomarkers for predicting CVDs. A comprehensive literature review revealed that a substantial portion of the diagnostic biomarkers identified have previously been associated with CVD. The framework we propose in this study is unbiased and generalizable to other diseases and disorders. [ABSTRACT FROM AUTHOR]

In military populations, gene-environment interactions can influence performance and health outcomes. Brain-derived neurotrophic factor (BDNF) is a central nervous system protein that is important for neuronal function and synaptic plasticity. A BDNF single nucleotide polymorphism, rs6265, leads to an amino acid substitution of valine (Val) with methionine (Met) at codon 66 (Val66Met), which may influence an individual's response to occupational stress, and predispose military members to psychological disorders. Telomere length (TL), a novel measure of biological aging, can be used as a biomarker of stress. Accordingly, telomere shortening may be a surrogate indicator of physiological weathering due to chronic disease and stressful life events. To increase our understanding about the potential effect of the Val66Met mutation on the human stress response, we evaluated the relationships between Val66Met, TL, and mental health symptoms in a military population. In this pilot study (N = 164), we observed an association between Val66Met and reduced TL (p = 0.048). There was no relationship between Val66Met and mental health symptoms. These results support the investigation of gene-environment interactions, and their potential influence on TL due to occupational stress such as military service. [ABSTRACT FROM AUTHOR]

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]