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PubMed2025

Opportunistic screening for broad range of medically relevant secondary findings: Laboratory benefits and burdens.

PURPOSE: Exome and genome sequencing enable opportunistic screening for secondary findings (SFs). We report on exome analysis for a broad range of medically relevant SFs in the setting of the Incidental Genomics randomized clinical trial (NCT03597165). METHODS: Participants had exome sequencing and were randomized to receive only primary cancer findings (control) or cancer findings and a choice of SFs (intervention). RESULTS: Across 279 participants, there were 4441 unique variants in SF genes: 5.0% (221) were reportable pathogenic/likely pathogenic variants, and 81.4% (3615) were nonreportable variants of uncertain significance (VUS). Intervention arm participants had on average 2.6 (SD 1.66, range 0-9) pathogenic/likely pathogenic variants and 29.5 VUS (SD 13.2, range 2-74). SFs for monogenic disease risk were reported in 35.3% (49/139) of participants (American College of Medical Genetics and Genomics non-cancer subset in 1.4%) and carrier status in 89.3% (117/131). In the intervention arm, variant filtration was 7.7 times longer per case (95% CI 5.3 to 11.3, P < .0001), variant classification was 13.3 times longer (95% CI 10.6 to 16.5, P < .0001), and report preparation was 3.3 times longer (95% CI 2.6 to 4.1, P < .0001). CONCLUSION: Although the yield of reportable SFs was high, this was accompanied by many nonreportable VUS and increased efforts for exome analysis.

Humans↗

PubMed2025

Implementing secondary findings analysis in a genetic and environmental research study.

PURPOSE: Optimizing return of secondary findings (SFs) in research settings requires an understanding of the complexities and challenges. METHODS: Genome sequence was generated for 4737 participants in a genetic and environmental health study, and 4630 of them consented to SF return. Variants in the American College of Medical Genetics and Genomics v3.0 genes were classified using the American College of Medical Genetics and Genomics/Association for Molecular Pathology criteria with ClinGen-approved modifications. RESULTS: Eighty-six variants were eligible for return to 102 participants. Average time to initial recontact attempt was 5.8 years. Recontact attempts reached 95 of 102 individuals. Results were returned to 57 participants. The remainder passively declined (25), actively declined (11), were lost to follow-up (5), were deceased (3), or had prior knowledge of the result (1). Return of results was positively associated with education status (2 × 3 C2, P = .0035). CONCLUSION: The interest in receiving SFs was high at the time of consenting, but a clinically validated result was returned to just over half of the individuals with an SF. Approximately 1 in 3 participants with an SF who had consented to receive them subsequently actively or passively declined receipt of the result. Given the health importance of return of SF, minimizing the time from consent to results return and tailoring outreach to education level may optimize uptake of SF return.

Adult↗

PubMed2025

Evaluating the return of additional findings from the 100,000 Genomes Project: A mixed-methods study exploring participant experiences of receiving secondary findings from genomic sequencing.

PURPOSE: The 100,000 Genomes Project participants could consent to receive additional findings (AFs) for variants associated with susceptibility to cancer and familial hypercholesterolemia. Here, we evaluate stakeholder experiences to inform clinical practice. METHODS: Mixed-methods study conducted at 18 sites across England that comprised a cross-sectional survey and interviews with participants who received a positive AF (PAF) and interviews with participants who had no AFs (NAF). RESULTS: There were 146 surveys followed by 35 interviews with PAF participants and 29 interviews with NAF participants. Surveys found that PAF results were seen as useful and would influence health management (82%). Most (90%) had shared their result with family members. Experiences differed by PAF type; cancer PAF participants were often initially shocked and anxious and found telling family members challenging compared with participants with a familial hypercholesterolemia PAF. Although most experiences of NAF results were positive, some misunderstandings were identified. Participants supported returning AFs when offering genome sequencing. CONCLUSION: Patient experiences of receiving AFs were primarily positive, and there is support for offering AFs routinely. Considerations for offering AFs in clinical practice include adapting approaches tailored to individual conditions and greater support for people with a NAF result.

Humans↗

PubMed2025

Costs and cost-effectiveness of returning secondary findings from genomic sequencing based on the return of additional findings in the 100,000 Genomes Project.

PURPOSE: To assess costs and cost-effectiveness of returning additional findings from genome sequencing using data from the 100,000 Genomes Project (100kGP). METHODS: A model-based cost-utility analysis combining yield, consent rates, and cost data from the 100kGP with published estimates of downstream costs and quality-adjusted life years expected to accrue over a lifetime, after the identification of a pathogenic variant. RESULTS: The cost of returning additional findings to participants in the 100kGP was £7.1m or £81 per participant, with a yield of 0.85% for consented participants. The estimated lifetime incremental cost per participant was £125 and quality-adjusted life years 0.004, giving an incremental cost-effectiveness ratio of £28,830. Implementing a policy of returning additional findings is unlikely to be cost-effective (ie, 13%) at a willingness-to-pay threshold of £20,000. A short-term cost of returning findings of £43 per participant or lower (compared with the base case of £81) would result in an incremental cost-effectiveness ratio of less than £20,000. Alternatively, cost-effectiveness may be improved by returning additional findings to younger patient populations. CONCLUSION: Return of additional findings following genome sequencing for this group of conditions may not be a cost-effective use of health care system resources. Our cost-effectiveness outcomes rely on published estimates and should be validated through long-term follow-up data.

Humans↗

PubMed2026

Recommendations for return of secondary genomic findings in observational cohort studies.

The return of secondary genomic findings (ROSF) to participants in observational cohort studies has evolved from a topic of debate to an accepted standard. This Perspective synthesizes the proceedings of a 2024 National Heart, Lung and Blood Institute-sponsored workshop and the broader literature to provide updated guidance for ROSF. Building on the 2010 National Heart, Lung and Blood Institute Working Group recommendations and the 2014 Clinical Sequencing Exploratory Research/Electronic Medical Records and Genomics 'floor and ceiling' framework, we address four areas: an integrated ethical framework for observational cohort settings; the emerging challenge of returning novel result types beyond monogenic variants, including polygenic risk scores, somatic mosaicism and pharmacogenomic findings; health equity and community engagement as structural prerequisites for ethical ROSF; and scalability challenges, including technology-assisted disclosure. Drawing on implementation experience from large-scale sequencing programs, we offer recommendations that balance researcher obligations with participant autonomy and equitable access to the benefits of genomic research.

Journal Article↗

PubMed2024

Opportunistic genomic screening has clinical utility: An interventional cohort study.

PURPOSE: Practice is shifting toward genome-first approaches, such as opportunistic screening for secondary findings (SFs). Analysis of SFs could be extended beyond medically actionable results to include non-medically actionable monogenic disease risks, carrier status, pharmacogenomic variants, and risk variants for common complex disease. However, evidence on the clinical utility of returning these results is lacking. We assessed the outcomes of opportunistic screening for a broad spectrum of SFs by evaluating the yield, impact on clinical management, and consistency between SFs and participants' clinical features and family history. METHODS: Adult cancer patients had exome sequencing with the option to learn multiple categories of SFs. Outcomes data were collected through chart review and participant-reported measures up to one year after return of results. RESULTS: All participants (n = 139, 85.6% female, average 54.6 years old) who elected to learn SFs had ≥1 variant reported (100% [139/139]). The yield of reportable findings was highest for pharmacogenomic variants (97.8% [135/138] of participants), followed by common disease risk variants (89.4% [118/132]), carrier status (89.3% [117/131]), and variants related to Mendelian (27.2% [34/125]), medically actionable (15.2% [21/138]), and early-onset neurodegenerative (2.6% [3/117]) disease risks. SFs from the American College of Medical Genetics and Genomics list (v3.2, noncancer genes) were reported in 1.4% (2/138) of participants. SFs across all categories demonstrated clinical utility by prompting management changes in 28.1% (39/139) of participants. Moreover, a considerable proportion of participants had suggestive clinical features (49.0% (24/49)]) or family history (21.8% (27/124)) potentially related to their SFs. CONCLUSION: Our findings indicate there are potential benefits from opportunistic screening for a broad range of SFs.

Humans↗

PubMed2024

Diagnosing missed cases of spinal muscular atrophy in genome, exome, and panel sequencing data sets.

PURPOSE: We set out to develop a publicly available tool that could accurately diagnose spinal muscular atrophy (SMA) in exome, genome, or panel sequencing data sets aligned to a GRCh37, GRCh38, or T2T reference genome. METHODS: The SMA Finder algorithm detects the most common genetic causes of SMA by evaluating reads that overlap the c.840 position of the SMN1 and SMN2 paralogs. It uses these reads to determine whether an individual most likely has 0 functional copies of SMN1. RESULTS: We developed SMA Finder and evaluated it on 16,626 exomes and 3911 genomes from the Broad Institute Center for Mendelian Genomics, 1157 exomes and 8762 panel samples from Tartu University Hospital, and 198,868 exomes and 198,868 genomes from the UK Biobank. SMA Finder's false-positive rate was below 1 in 200,000 samples, its positive predictive value was greater than 96%, and its true-positive rate was 29 out of 29. Most of these SMA diagnoses had initially been clinically misdiagnosed as limb-girdle muscular dystrophy. CONCLUSION: Our extensive evaluation of SMA Finder on exome, genome, and panel sequencing samples found it to have nearly 100% accuracy and demonstrated its ability to reduce diagnostic delays, particularly in individuals with milder subtypes of SMA. Given this accuracy, the common misdiagnoses identified here, the widespread availability of clinical confirmatory testing for SMA, and the existence of treatment options, we propose that it is time to add SMN1 to the American College of Medical Genetics list of genes with reportable secondary findings after genome and exome sequencing.

Humans↗

PubMed2026

Detection rate of pathogenic variants by postmortem genetic testing for sudden cardiac death among children and young adults: systematic review and meta-analysis.

PURPOSE: Postmortem genetic testing (PMGT) can clarify the causes of sudden cardiac death (SCD) in children and young adults and provide preventive care for relatives. We systematically reviewed studies to estimate the detection rate of pathogenic variants identified by PMGT in SCD cases aged 1-50 years and examined factors influencing detection rates. METHODS: Ovid MEDLINE and Ovid Embase were searched for observational studies on PMGT in cases of SCD, records in duplicate were screened, and study- and variant-level data were extracted. Risk of bias was assessed using the Joanna Briggs Institute checklist. The pooled detection rates were estimated using random-effects meta-analysis, and heterogeneity was explored based on subgroup and meta-regression analyses. RESULTS: Sixty-six studies (4,452 cases from 23 countries) were included. The pooled detection rate was 19% (95% confidence interval, 15% to 24%). Among the detected pathogenic variants, 76% were found in genes included on the ACMG Secondary Findings list. Higher detection rates were associated with earlier publication years, lower mean age, and lower risk of bias. Substantial between-study heterogeneity persisted (I2 = 91%) despite the subgroup and meta-regression analyses. CONCLUSION: PMGT can be used to identify pathogenic variants in young SCD cases, however, there is considerable heterogeneity in study conditions.

Forensic genetics↗

PubMed2025

[Achievements and Expectations of the Rare Disease Diagnostic Support Program in the Republic of Korea].

OBJECTIVES: The Rare Disease Diagnostic Support Program in the Republic of Korea aims to improve early diagnosis and diagnostic yield for patients with rare diseases, particularly for those residing in non-metropolitan areas, by providing whole genome sequencing (WGS) services through regional medical institutions. This study evaluated the performance of the program, focusing on its clinical utility, including early diagnosis and treatment linkage, and its policy impact related to patient benefits. METHODS: From August 2024, WGS was performed on 410 patients with suspected rare diseases at 23 institutions outside the metropolitan area. A one-stop diagnostic pathway was established to perform sample collection, test referral, report delivery, and genetic counseling within a single clinical flow based on the patient’s location of residence. Sequencing was performed by external laboratories. RESULTS: Among the 410 patients, pathogenic variants were identified in 129 (31.5%), with a turnaround time of 28 days. Of those diagnosed, 78.2% received treatment benefits via national programs such as co-payment exemption and medical expense support programs. Approximately 30% of the patients were eligible for therapeutic intervention, particularly medication or dietary therapy. Family genetic testing of three members identified potential carriers or high-risk groups in 28 households (65.1%). Consent for secondary findings was 99.0%, with clinically significant variants found in 3.9% of cases. CONCLUSIONS: The program demonstrated clinical value by improving diagnostic accessibility, reducing regional disparities, facilitating timely treatment, and supporting preventive care through family risk identification. These findings support the need for sustainable expansion of genome-based diagnostic services in the national health policy.

Diagnosis↗

PubMed2025

Heat-Induced Secondary Dormancy Contributes to Local Adaptation in Arabidopsis thaliana.

Seeds should not germinate in conditions unsuitable for seedling growth. Dormancy, which allows seeds to remain inactive in an environment that would otherwise enable germination, helps optimise the timing of germination. Primary dormancy, developed during seed maturation on the parent plant, prevents immediate germination post-dispersal, regardless of external conditions. Secondary dormancy, however, is triggered post-dispersal when seeds face unfavourable conditions, enabling them to re-enter dormancy even if initially non-dormant. This mechanism allows seeds to fine-tune germination according to environmental conditions. In this study, we examined the role of heat-induced secondary dormancy in local adaptation by analysing natural variations within 361 Arabidopsis thaliana accessions from across Europe. We discovered that secondary dormancy acquisition varies with primary dormancy levels and after-ripening. Both primary and heat-induced secondary dormancy exhibited adaptive clines along temperature and precipitation gradients, with secondary dormancy showing a steeper cline, indicating its significant role in local adaptation. Using species distribution models, we predicted that genotypes with high secondary dormancy would show greater resilience to future climate changes. Additionally, we identified specific genomic regions controlling secondary dormancy levels including a novel candidate gene for secondary dormancy variation. Our findings show that secondary dormancy is a complex adaptive mechanism and a predominant contributor to the dormancy trait syndrome that favours plant survival in habitats exposed to harsh summers.

Arabidopsis↗

PubMed2024

Offering complex genomic screening in acute pediatric settings: Family decision-making and outcomes.

PURPOSE: Families of children in pediatric acute care who are offered ultrarapid genomic sequencing are making complex decisions during a high-stress period. To reduce complexity for families and clinicians, we offered genomic screening for the child and parents after the completion of diagnostic testing. We evaluated uptake, understanding, and service delivery preferences. METHODS: A cohort of 235 families who had completed ultrarapid diagnostic genomic sequencing at 17 Australian hospitals were offered up to 3 screens on their genomic data: pediatric-onset, adult-onset, and expanded couple carrier screening. We investigated decision making, understanding, and service delivery preferences using surveys at 3 time points (pre counseling, post counseling, and post result) and performed inductive content analysis of pretest genetic counseling transcripts. RESULTS: A total of 119 families (51%) attended genetic counseling with 115 (49%) accepting genomic screening. Survey respondents were more likely to find decisions about couple carrier screening easy (87%) compared with adult (68%; P = .002) or pediatric (71%; P = .01) screening decisions. All respondents with newly detected pathogenic variants accurately recalled this 1 month later. A delayed offer of screening was acceptable to most respondents (78%). CONCLUSION: Separating genomic screening from the stressful diagnostic period is supported by families who demonstrate good knowledge and recall. Our results suggest delaying genomic screening should be trialed more widely.

Humans↗

PubMed2026

Argument in Favor of Reporting Adult-onset Conditions in Prenatal Diagnosis.

Prenatal genomic sequencing can detect far more than clinicians conventionally report. Whether adult-onset conditions diagnosed in the fetus should be disclosed prenatally remains debated, and most laboratories and guidelines restrict reporting to childhood-onset disease. We argue that this restriction is not supported by available evidence. Prospective parents consistently elect to receive adult-onset findings, most often to plan for a child's future health. Pediatric and newborn sequencing studies have not demonstrated the psychological, relational, or developmental harms critics anticipated, and pregnancy offers an unmatched opportunity to reach an otherwise unscreened population. Policy should be guided by informed consent and patient autonomy.

adult-onset conditions↗

PubMed2025

The burden of TTN variants in the genomic era: Analysis of 18,462 individuals from the Solve-RD consortium and general recommendations.

PURPOSE: Titin, the largest protein in the human body, has been associated with several disease phenotypes caused by variants in the TTN gene. With around 20% of the population carrying a rare TTN variant and over 60 million genomes expected to have been sequenced worldwide by 2025, interpreting these findings presents major challenges. This study analyzed TTN variants in the Solve-RD cohort, the European network for unsolved rare disease cases. METHODS: We collected data from 11,072 individuals with suspected rare diseases and 7390 healthy relatives from the Solve-RD consortium, checking and manually reviewing TTN variants. We then used a filtering approach focused on clinical relevance, and we provided updated recommendations based on recent literature. RESULTS: Among the cohort, 240 individuals (1.3%) carried at least one heterozygous TTN truncating variant (TTNtv), with a 3.8% prevalence in the neuromuscular subgroup, primarily composed of unsolved cases. Four individuals received a titinopathy diagnosis. Additionally, 99 participants (0.5%) had a TTNtv in a high cardiac percent spliced in exon (>80%), and 4 had an overt cardiomyopathy. CONCLUSION: This study highlights the need for standardized approach to TTN variants, and investigation of missing heritability in individuals with skeletal myopathy with het TTNtv. Establishing consensus on percent spliced in-based thresholds will be essential for assessing cardiac risk and guiding the management of asymptomatic individuals.

Humans↗

PubMed2026

Metabolic ketosis attenuates NLRP3 inflammasome activation and is associated with improvements in hepatic steatosis and liver stiffness in MASLD: a pilot randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic-inflammatory disorder in which metabolic stress and innate immune activation, particularly through the NLRP3 inflammasome, contribute to disease progression. Metabolic ketosis, characterized by increased levels of circulating ketone bodies, especially β-hydroxybutyrate, has emerged as a promising strategy to modulate substrate utilization, inflammatory signaling, and hepatic injury. However, clinical evidence integrating molecular, metabolic, and hepatic outcomes remains limited. METHODS: In this pilot randomized controlled trial, 20 participants with newly diagnosed MASLD were randomly assigned to either a 3-month intervention with a daily C8-enriched medium-chain fatty acid formulation (m-CAP; meta-Capridin, providing approximately 20 g/day of C8) or a standardized low-carbohydrate dietary protocol. Metabolic indices, inflammatory mediators, adipokines, and hepatic enzymes were assessed. The expression of key inflammasome components (NLRP3, caspase-1, and ASC) was evaluated in peripheral blood mononuclear cells, and hepatic steatosis and liver stiffness were measured via transient elastography. RESULTS: The C8-enriched intervention was associated with increased circulating β-hydroxybutyrate levels, indicating the achievement of nutritional ketosis. Changes over time were observed in metabolic parameters, including fasting serum glucose (p < 0.05), HOMA-IR (p < 0.05), body fat percentage (p < 0.05), and BMI (p < 0.05). Alterations in inflammatory mediators and adipokine-related outcomes were also observed following the intervention. At the molecular level, changes in inflammasome-related markers were detected, including caspase-1 mRNA expression (p < 0.05) and NLRP3 expression at the transcriptional (p < 0.05) and protein levels (p < 0.01), whereas ASC expression remained unchanged. Changes in hepatic steatosis (p < 0.01) and liver stiffness measurements were observed following the intervention. Given the absence of significant Group × Time interactions for several secondary outcomes, these findings should be interpreted as exploratory and hypothesis-generating. CONCLUSIONS: Induction of metabolic ketosis was associated with changes in metabolic, inflammatory, and hepatic parameters in patients with MASLD. The observed associations between ketosis, inflammasome-related markers, and noninvasive liver outcomes warrant further investigation of ketosis-based interventions as adjunctive approaches in MASLD. Larger and longer-term clinical trials are needed to confirm these findings and to determine whether short-term changes in liver stiffness reflect sustained alterations in hepatic status rather than structural fibrosis regression. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); Unique identifier: IRCT20170315033086N12; Registration date: 19 September 2024; Registry URL: https://www.irct.ir. IRCT is a primary registry in the WHO Registry Network (https://www.who.int/tools/clinical-trials-registry-platform/network/primary-registries).

Humans↗

PubMed2026

Two Saccharopolyspora isolates from archaeological excavation sites: polyphasic taxonomy, biosynthetic potential, bioactivity profiling and description of Saccharopolyspora antiqui sp. nov.

Archaeological excavation sites represent underexplored microbial habitats with the potential to recover taxonomically and biotechnologically valuable actinomycetes. In this study, two Saccharopolyspora strains, 5N708T and 5N102, were isolated from soil samples collected from the Gaziantep-Doliche-Dülük and Bitlis-Ahlat-Selçuklu Cemetery archaeological excavation sites in Türkiye. A polyphasic taxonomic approach, including 16S rRNA gene sequencing, phylogenetic and phylogenomic analyses, average nucleotide identity, digital DNA-DNA hybridization, phenotypic characterization, and chemotaxonomic analyses, showed that strain 5N708T represents a novel species of the genus Saccharopolyspora, for which the name Saccharopolyspora antiqui sp. nov. is proposed, whereas strain 5N102 was assigned to Saccharopolyspora elongata. Both isolates were further evaluated for their antimicrobial, antioxidant, and cytotoxic activities, and their biosynthetic potential was investigated by genome mining. Both strains showed activity against Staphylococcus aureus, with strain 5N708T producing the larger inhibition zone. Strain 5N102 exhibited markedly stronger antioxidant activity than strain 5N708T in radical scavenging, ferric reducing antioxidant power, and reducing power assays. In contrast, strain 5N708T showed more promising cytotoxic activity, with relative selectivity toward MIA PaCa-2 pancreatic cancer cells compared with HEK293 cells after prolonged incubation. Genome mining revealed multiple biosynthetic gene clusters in both isolates, supporting their capacity to produce secondary metabolites. These findings indicate that archaeological soils are promising reservoirs of taxonomically novel and biologically active Saccharopolyspora strains.

Saccharopolyspora↗

PubMed2026

Optimization of protoplast based DNA isolation and genome analysis in a gamma-irradiated Aspergillus niger mutant strain.

Aspergillus niger is an important industrial fungus widely used for citric acid production and a range of biotechnological applications. In this study, a protoplast-based DNA isolation protocol was optimized for a gamma-irradiated A. niger AN-L103_M1 mutant strain, followed by whole-genome sequencing and functional genome analysis. Protoplast yield was strongly influenced by enzyme concentration and the molarity of the osmotic stabilizer. The highest yield was achieved at an enzyme concentration of 50 mg/mL (2.487 ± 0.04 × 10⁸ cells/mL) and 0.8 M KCl (2.550 ± 0.06 × 10⁸ cells/mL), with both factors showing significant effects (p < 0.0001) in GraphPad Prism 11.0.0. Whole-genome sequencing performed using an Illumina NovaSeq 6000 platform yielded a 37.06 Mb draft genome assembled into 537 contigs, with an N50 of 363,084 bp and a GC content of 48.2%. BUSCO 14 analysis showed high completeness (97.95% complete BUSCOs). Functional annotation and KEGG pathway mapping identified genes involved in glycolysis, the tricarboxylic acid cycle, and citrate biosynthesis, while biosynthetic gene cluster analysis revealed diverse potential for secondary metabolite production. These findings provide an optimized workflow for protoplast-based DNA isolation and genome-scale functional analysis in A. niger, proposing a basis for future comparative genomics, transformation studies, and experimentally validated metabolic engineering.

Aspergillus niger↗

PubMed2026

Genomic Regions Associated with Resistance to Soybean Cyst Nematode (Heterodera glycines Ichinohe) Population HG Type 1.2.5.7 in Dry Beans (Phaseolus vulgaris L.).

North Dakota, the largest dry bean (Phaseolus vulgaris L.) producing state in the U.S., faces an emerging production threat caused by the soybean cyst nematode (SCN; Heterodera glycines Ichinohe, 1952). Host resistance is an effective management strategy, yet resistance to the virulent SCN population HG type 1.2.5.7 has not been genetically characterized in dry beans. In this study, 170 dry bean genotypes (113 breeding lines/cultivars and 57 germplasm accessions) were evaluated for response to HG type 1.2.5.7 under controlled conditions using female index (FI) as the resistance phenotype. FI values ranged from 4.1% to 78.1%, with one genotype (PI 313733) classified as resistant, 35 moderately resistant, 104 moderately susceptible, and 30 susceptible. Genome-wide association analysis using 2,044 single-nucleotide polymorphism (SNP) markers from the 3.8K Bean Panel chip and the BLINK model identified four significant marker-trait associations on chromosomes Pv02, Pv05, Pv07, and Pv11. Linkage disequilibrium-defined candidate intervals spanned 108 kb (Pv02), 1.50 Mb (Pv05), 798 kb (Pv07), and 1.45 Mb (Pv11), collectively containing 126 annotated genes: 20 on Pv02, 39 on Pv05, 35 on Pv07, and 32 on Pv11. The intervals contained putative genes annotated for signaling and transcriptional regulation, cell wall and carbohydrate metabolism, transport, and secondary metabolism. Together, these findings indicate that the response to HG type 1.2.5.7 in dry bean is quantitative and associated with multiple genomic regions. The identified intervals provide candidate targets for independent validation, fine mapping, functional analysis, and future marker development to support breeding for SCN resistance.

Disease Resistance↗

PubMed2025

Identification of an antifungal lipopeptide from Bacillus amyloliquefaciens HAU3 inhibiting the growth of Fusarium graminearum using preparative chromatography and 2D-NMR.

UNLABELLED: The presence of fungal contamination and its mycotoxins in animal feed is pervasive, posing a significant threat to the well-being and performance of animals, as well as the safety of animal-derived food products. In this work, we screened a strain of Bacillus amyloliquefaciens (B. amyloliquefaciens) HAU3 that exhibits efficient antifungal activity against the growth of Fusarium graminearum (F. graminearum). The antifungal activity was detected in the supernatant, with 20% sterile supernatant demonstrating an impressive antifungal rate of 98.46% against F. graminearum. The antifungal activity of the strain was evaluated through spectrum analysis and silage trials, revealing its effective antifungal activity against multiple fungal species. Furthermore, the strain is capable of degrading ZEN and its derivatives. The targeted disruption of fungal mycelial membrane was observed using scanning electron microscopy and transmission electron microscopy. Additionally, staining with the reactive oxygen species (ROS)-sensitive fluorogenic dye DCFH-DA and propidium iodide (PI) revealed that the strain induces accumulation of ROS in fungal mycelia. The active compounds underwent further separation, purification, and detection. The prominent active peak was identified through mass spectrometry and magnetic resonance spectroscopy. The molecular structure of the active compounds was predicted to be lipopeptides composed of 8 amino acids known as fengycin. The whole genome sequencing and informatics analysis unveiled a total of 13 gene clusters responsible for the synthesis of secondary metabolites. The antifungal effects of B. amyloliquefaciens HAU3 are exerted through the synthesis of fengycin, which selectively targets and compromises the integrity of fungal mycelia membranes, thereby making it a potential biocontrol agent for mitigating mycotoxin contamination in feed. IMPORTANCE: Mycotoxin contamination in animal feed, predominantly driven by Fusarium graminearum, represents a persistent threat to livestock health and food chain integrity. Here, we report the isolation of a soil-derived Bacillus amyloliquefaciens HAU3, exhibiting potent and broad-spectrum antifungal activity alongside efficient biodegradation of zearalenone and its derivatives. Mechanistic dissection reveals that fengycin, the principal bioactive metabolite, compromises fungal membrane integrity and elicits intracellular oxidative stress, culminating in hyphal collapse. Genomic profiling uncovers a diverse repertoire of biosynthetic gene clusters underpinning secondary metabolite production. These findings establish strain HAU3 as a promising microbial chassis for the development of next-generation biocontrol strategies aimed at mitigating mycotoxin burden in agroecosystems.

Bacillus amyloliquefaciens↗