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Results for “Rapid Genetic Testing”

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At least 19 recordsLinked to original sources

PubMed2026

Rapid genome sequencing identifies treatable conditions in non-intensive care unit hospitalized children.

PURPOSE: The utility of rapid genome sequencing (RGS) has been evaluated in pediatric intensive care unit (ICU) settings, but few studies have investigated its use in non-critically ill hospitalized children. Our study assesses the impact of RGS use in the non-ICU setting. METHODS: We analyzed RGS results obtained for hospitalized children from 2019 to 2023 and evaluated the impact on non-ICU patient care. Changes in management were determined via chart review of the first 30 days after testing. RESULTS: RGS was performed on 422 individuals: 339 ICU and 83 non-ICU. The diagnostic rate was 39% (32 of 83) in non-ICU and 35% (120 of 339) in ICU patients. Eighty-one percent of diagnostic RGS results in non-ICU patients had a management change within 30 days, and 56% (18 of 32) received a disease-targeted intervention, including medication or diet change, listing for transplant, or connection with a clinical trial. Of the children who received these intervention changes, the most common disease categories were metabolic (61%, 11 of 18) and epilepsy (22%, 4 of 18). CONCLUSION: RGS is effective at identifying treatable diagnoses in the non-ICU setting, with most patients experiencing a change in their care, and over half receiving disease-focused interventions. Our results support the utility of RGS in non-ICU hospitalized children and can impact providers' decision-making and payer coverage.

Genome sequencing↗

PubMed2026

Genetic testing practices across European epilepsy centers: An ERN EpiCARE survey.

OBJECTIVE: Genetic testing plays an increasing role in the diagnostic pathway for rare and complex epilepsies. However, significant heterogeneity persists in access, implementation, and interpretation across Europe. This study aimed to assess genetic testing practices, accessibility, and challenges across expert epilepsy centers within the European Reference Network for Rare and Complex Epilepsies (ERN EpiCARE) and to identify key challenges and areas for harmonization. METHODS: A cross-sectional survey was developed by the ERN EpiCARE Clinical Genetics Working Group and distributed to 50 EpiCARE member centers across 27 European countries. The questionnaire collected quantitative and qualitative information on available genetic testing modalities, turnaround times, use of rapid testing, multidisciplinary team (MDT) organization, genetic counseling practices, and perceived challenges. Survey findings were complemented by a structured discussion held during the ERN EpiCARE General Assembly. RESULTS: Responses were received from 46 centers (51 responses). Most centers reported access to genetic testing, predominantly through in-house facilities. Whole-exome sequencing was available in 85% of centers, and gene panels were available in 78%. Whole-genome sequencing was available in 59% of centers, frequently restricted to research or performed externally. Turnaround times for standard genetic testing were most commonly between 1 and 6 months. Genetic testing strategies varied by epilepsy subtype, with gene panels most frequently used as first-tier testing, and exome sequencing preferentially applied in developmental and epileptic encephalopathies. Considerable heterogeneity was observed in MDT organization, access to genetic counseling, reimbursement, data-sharing and registry infrastructures. SIGNIFICANCE: Although genetic testing is widely available across ERN EpiCARE centers, substantial disparities persist in its organization, accessibility, and implementation. Addressing these gaps through strengthened multidisciplinary collaboration, harmonized diagnostic strategies, and enhanced European-level coordination will be essential to ensure equitable access to high-quality genetic care for individuals with epilepsy. PLAIN LANGUAGE SUMMARY: Genetic testing is increasingly integrated in the diagnostic pathway for rare and complex epilepsies and treatment decisions. An ERN EpiCARE survey assessed how genetic testing is implemented across specialist epilepsy centers in Europe and identified persistent organizational, financial, and clinical barriers. Although most centers had access to advanced genomic testing, important differences were identified in access, reimbursement, turnaround times, and multidisciplinary expertise. European collaboration and harmonized practices are needed to support equitable access to high-quality genetic care for people living with epilepsy.

European reference networks↗

PubMed2026

Engineering CRISPR for Point-of-Care Tests.

CRISPR-based molecular diagnostics have emerged as powerful and programmable platforms that enable sensitive and specific detection for disease management and epidemiological surveillance. Advances in CRISPR engineering and assay design are driving the emergence of next-generation detection platforms that are highly sensitive, rapid, and amenable to field deployment. These engineering breakthroughs have the potential to reshape point-of-care tests (POCT) and transform how emerging and persistent health threats are monitored in decentralized and resource-limited settings. Herein, we systematically review the recent advancements in CRISPR engineering strategies aimed at improving detection sensitivity and specificity, eliminating the dependence on preamplification, and enabling robust POC deployment. The discussed strategies encompass both the rational engineering of CRISPR ribonucleoproteins (RNPs) and the optimization of downstream signaling modules for molecular diagnostic applications. We further highlight key challenges and future perspectives that may inspire impactful research directions and accelerate the advancement of CRISPR engineering strategies toward robust, field-deployable POCT platforms.

CRISPR-Cas Systems↗

PubMed2025

Long-term follow-up of children who received rapid genomic sequencing.

PURPOSE: To explore long-term trajectories of children who received rapid genome sequencing (RGS) in intensive care settings. METHODS: We examined the electronic health records of 67 critically ill pediatric patients who received RGS 6 to 8 years ago with a collective initial diagnostic yield of 46%. RESULTS: The median length of follow-up was 6.2 years (interquartile range 4.0-7.2 years). RGS-diagnosed patients had a longer average follow-up time compared with undiagnosed patients (5.9 years vs 4.8 years, P = .026) and more subspecialty appointments per follow-up year (9.4 vs 6.9, P = .036). Mortality during the follow-up period was 9%. Patients averaged 2.1 hospital readmissions per follow-up year and 28.1 hospitalized days per follow-up year. Forty-four patients (66%) had a documented new phenotype in the electronic health records during their follow-up period. Seven patients received clinician-driven reanalysis during the follow-up period, yielding 1 new diagnosis. Systematic reanalysis of RGS performed as part of this study identified 4 new candidate diagnoses. CONCLUSION: Pediatric patients who receive RGS during intensive care unit hospitalizations continue to be high health care utilizers in subsequent years, regardless of whether RGS identified a diagnosis. Additionally, two-thirds of this cohort had a documented phenotypic change over the follow-up period, indicating dynamic clinical evolution in the years after RGS.

Humans↗

PubMed2026

Mapping the development pipeline of genomic point-of-care tests: a horizon scan.

INTRODUCTION: As precision medicine increasingly relies on genetic information, the development of reliable genomic point-of-care tests (POCTs) is essential. However, the number of technologies that have reached true clinical usability is limited. There is a growing need for POCTs that enable rapid, accurate analysis of human genetic variation, particularly across diverse clinical settings without requiring specialist expertise. AREAS COVERED: This horizon scan aimed to provide an overview of the development pipeline of POCTs to identify variation(s) in the genome and epigenome that enable the use of genetic information to inform diagnosis, prognosis, and treatment decisions in any clinical area. Database (Embase and MEDLINE) and clinical trial registry (ClinicalTrials.gov) searches were conducted from 2019 to 19 December 2024; 346 unique technologies were identified. EXPERT OPINION AND COMMENTARY: A range of purposes and conditions were identified; the most common being diagnosis (n = 263) and cancer (n = 237) respectively. We defined 'true POCTs' as those that were highly automated, capable of analyzing complex samples, and operable by non-specialists. Only 36 met these criteria; six are already on the market, one is in clinical trials, and the remaining 29 are at various stages of development. Overall, most technologies were in early stages of development, highlighting the need for further innovation and validation.

Point-of-care↗

PubMed2025

Molecular insights into the persistence and co-occurrence of two different carbapenem-resistant Pseudomonas aeruginosa lineages within a hospital setting.

UNLABELLED: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) represents a critical-priority pathogen capable of causing life-threatening, multidrug-resistant infections. We performed susceptibility testing, whole-genome sequencing, and bioinformatic analyses on 137 CRPA isolates from a Guangdong hospital. We found that the major specimen types were respiratory specimens (57/137, 41.6%) and bronchoalveolar lavage (42/137, 30.7%). All isolates were carbapenem-resistant but had low resistance to polymyxin B (0.7%, 1/137). IncP-6-positive isolates exhibited ≥2- to 32-fold higher resistance to 9/12 antibiotics (P < 0.05), with no difference to imipenem and meropenem. Fifty-four sequence types and 11 O-serogroups were identified, with ST1971 (6.6%) and O11 (29.9%) being predominant. Temporal and spatial patterns suggest persistent co-occurrence of clade 1 and clade 2 isolates, indicating potential nosocomial outbreak and clonal transmission. IMPORTANCE: The prevalence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) has increased rapidly in recent years, yet few genetic and epidemiological studies on CRPA isolates have been performed. We performed susceptibility testing, whole-genome sequencing, and bioinformatic analyses on hospital isolates to investigate their resistance profiles and molecular epidemiology. These findings may offer new insights for developing effective global strategies to control CRPA and reduce untreatable infections in clinical settings.

Pseudomonas aeruginosa↗

PubMed2026

Guidelines for Genetic Testing of Peripheral Nerve Disorders.

Inherited peripheral neuropathies (IPNs) comprise a clinically and genetically heterogeneous group of disorders affecting approximately 1 in 2500 individuals and represent one of the most common inherited neurologic diseases. The rapidly expanding identification of disease-causing genes and the widespread implementation of next-generation sequencing (NGS) have fundamentally transformed the diagnostic evaluation of these disorders. Contemporary molecular testing has substantially increased diagnostic yield, shortened the diagnostic delay, refined disease classification, and strengthened genotype-phenotype correlations. In the United States, NGS-based multigene panels have become the most cost-effective first-line molecular diagnostic approach for most patients with suspected inherited neuropathies, whereas phenotype-directed single-gene testing remains appropriate in selected clinical circumstances and in healthcare systems in which access to comprehensive sequencing is limited. Despite these advances, challenges continue to affect diagnostic accuracy, including interpretation of variants of uncertain significance, detection of copy number variants and repeat expansions, technical limitations associated with highly homologous genomic regions such as SORD, and variability in gene content and analytic performance among commercially available testing platforms. Accurate diagnosis therefore requires integration of clinical phenotype, electrodiagnostic findings, family history, and molecular data. Establishing a precise genetic diagnosis has become increasingly important because it improves prognostic accuracy, guides genetic counseling and cascade testing, identifies patients with treatable hereditary neuropathies such as transthyretin amyloidosis, and facilitates enrollment in gene-specific clinical trials and emerging precision therapies. An evidence-based, phenotype-driven approach that incorporates contemporary molecular technologies is essential to maximize diagnostic efficiency while recognizing the strengths and limitations of currently available genetic testing strategies.

Charcot–Marie–tooth disease↗

PubMed2026

Field-isolate recombinant tick-borne encephalitis viruses define reporter-stability guidelines for antiviral testing in flaviviruses.

As arthropod-borne viruses continue to threaten populations globally, there is a pressing need for experimental systems that enable rapid antiviral discovery. Reverse-genetics platforms producing recombinant reporter orthoflaviviruses have been developed to address this gap. Here, we present two new recombinant tick-borne encephalitis viruses (TBEVrec) generated on a European-subtype Haselmühl Tiho1 isolate backbone. A reporter gene, either eGFP or Nluc, was inserted in the capsid-coding region of the genome downstream of the capsid RNA regulatory signal and separated from the complete viral polyprotein by a 2A self-cleaving peptide. TBEVrec was better rescued using the circular polymerase extension reaction (CPER) than with the infectious subgenomic amplicon (ISA) method. TBEVrec replicated efficiently in relevant human cell lines, with comparable replication to wild-type TBEV in a neuronal cell line and moderately reduced titers and RNA levels in immune-derived cell lines. Using either eGFP or Nluc, we illustrate how TBEVrec enabled high-content RNAi screening, highlighting Nucleolin and PRKD1 as potential TBEV host factors, and drug testing on a benchtop plate reader. Nanopore sequencing of the eGFP insert revealed that the reporter is excised without affecting flanking regions. Comparative analysis of eGFP and Nluc further shows that this instability is time- and cell type-dependent, and that Nluc is comparatively more stable. From these observations, we outline safeguards and design principles that are broadly applicable both to the rescue of existing constructs and to the design of future recombinant reporter virus platforms.

CPER↗

PubMed2026

Epilepsy of infancy with migrating focal seizures: A scoping review of clinical features, diagnostic testing including genetics, long-term outcomes, mortality, and current and emerging therapeutic strategies.

BACKGROUND: Epilepsy of infancy with migrating focal seizures (EIMFS) is among the most severe developmental and epileptic encephalopathies (DEEs), marked by intractable multifocal seizures migrating across both hemispheres, profound developmental arrest, and high early mortality. Advances in next-generation sequencing have revealed a heterogeneous genetic architecture dominated by KCNT1 gain-of-function variants across more than 30 implicated genes, creating opportunities for precision therapeutics. OBJECTIVE: To systematically map published evidence on the clinical, electrophysiological, neuroimaging, genetic, and therapeutic landscape of EIMFS, and to delineate critical knowledge gaps and future research priorities. METHODS: A scoping review was conducted following the Arksey and O'Malley framework, searching PubMed, Ovid MEDLINE, Embase, Cochrane Library/CENTRAL, and ClinicalTrials.gov. RESULTS: Of 643 articles screened, 89 met inclusion criteria. Beyond confirmation of the canonical electroclinical phenotype, several gaps emerged: neonatal versus post-neonatal onset stratification by genetic etiology remains largely uncharacterized; genotype-specific EEG biomarkers are lacking except for a single small KCNT1 study; and the clinical significance of atypical EEG features-including burst suppression and hypsarrhythmia-is undefined. Neuroimaging literature documents progressive cerebral atrophy and myelination abnormalities without quantitative volumetry, diffusion tractography markers, or attribution to seizure burden, medication effects, or underlying etiology. Genetic diagnostic yield was 70-80%, with KCNT1 accounting for 30-50% of solved cases; however, genotype-outcome stratification is limited. Seizures were broadly refractory; potassium bromide, ketogenic diet, cannabidiol, and quinidine (in KCNT1-confirmed cases) showed partial efficacy. Emerging precision approaches include sodium channel blockers for SCN2A gain-of-function variants, novel small molecules, fluoxetine, antisense oligonucleotides, and divalent siRNA targeting KCNT1. Systemic-to-pulmonary collateral circulation causing severe cardiopulmonary complications was reported across multiple cases, yet no consensus screening protocol exists. CONCLUSIONS: EIMFS remains one of the most refractory epilepsy syndromes of infancy. Precision genetic diagnosis is essential to guide targeted therapy. International collaborative registries, standardized outcome measures, genotype-stratified biomarker studies, and rapid point-of-care genomic testing are urgently needed to advance evidence-based care for this highly vulnerable population.

Humans↗

PubMed2026

Review: The African turquoise killifish as a model for the integrative physiology of vertebrate aging.

With increasing emphasis on extending healthy lifespan, aging research requires vertebrate models that permit efficient mechanistic investigation and intervention testing within practical time and cost constraints. The African turquoise killifish (Nothobranchius furzeri) has attracted growing attention because it combines an exceptionally short life cycle with an intact vertebrate physiological context and an expanding genetic toolkit, enabling relatively rapid evaluation of candidate aging interventions and mechanistic analysis across molecular, tissue, and organismal levels. This review assesses N. furzeri from an integrative-physiology perspective, focusing on germline-soma interactions, gut microbiota-host crosstalk, nutrient sensing and metabolic remodeling, temperature responsiveness, and AMPK-mTOR-linked programs. It also examines expanding genome-engineering and reporter approaches that support mechanistic and tissue-resolved investigation of these physiological processes. Building on recent reviews of killifish biology, disease modeling, regeneration, and the hallmarks of aging, we synthesize evidence across major intervention domains, distinguish established phenotypic effects from incompletely resolved mechanisms, and highlight functional endpoints, methodological standardization, and the appropriate interpretation of the model's translational relevance. Together, these features position N. furzeri as a strategically useful vertebrate platform for rapid mechanistic testing, intervention evaluation, and prioritization of aging-related pathways. Future progress will require improved methodological standardization, tissue-resolved causal studies, and question-driven cross-species validation where appropriate.

Animals↗

PubMed2024

Critically unwell infants and children with mitochondrial disorders diagnosed by ultrarapid genomic sequencing.

PURPOSE: To characterize the diagnostic and clinical outcomes of a cohort of critically ill infants and children with suspected mitochondrial disorders (MD) undergoing ultrarapid genomic testing as part of a national program. METHODS: Ultrarapid genomic sequencing was performed in 454 families (genome sequencing: n = 290, exome sequencing +/- mitochondrial DNA sequencing: n = 164). In 91 individuals, MD was considered, prompting analysis using an MD virtual gene panel. These individuals were reviewed retrospectively and scored according to modified Nijmegen Mitochondrial Disease Criteria. RESULTS: A diagnosis was achieved in 47% (43/91) of individuals, 40% (17/43) of whom had an MD. Seven additional individuals in whom an MD was not suspected were diagnosed with an MD after broader analysis. Gene-agnostic analysis led to the discovery of 2 novel disease genes, with pathogenicity validated through targeted functional studies (CRLS1 and MRPL39). Functional studies enabled diagnosis in another 4 individuals. Of the 24 individuals ultimately diagnosed with an MD, 79% had a change in management, which included 53% whose care was redirected to palliation. CONCLUSION: Ultrarapid genetic diagnosis of MD in acutely unwell infants and children is critical for guiding decisions about the need for additional investigations and clinical management.

Humans↗

PubMed2026

Development of a new recombineering system for Edwardsiella species.

Edwardsiella species are important aquaculture pathogens that also cause opportunistic infections in humans, necessitating efficient genome editing tools to study their pathogenesis and develop control strategies. In this study, we identified and characterized six endogenous recombinases pairs from Edwardsiella and its phages. Among these, the BAS_MS17 system exhibited the highest recombination efficiency in E. piscicida EIB202Δp. Extending homology arms from 150 bp to 200 bp improved editing efficiency by 2-fold, while the addition of Redg or Plug further enhanced recombination by 3-fold and 2.5-fold, respectively, without compromising accuracy (100%). More importantly, when applied to E. piscicida sdu12S, Redg or Plug improved the editing efficiency by 8-fold and 7-fold, respectively. Deletion of the phage-derived single-strand binding protein (SSB) reduced efficiency to 25% of the BAS_MS17 level, whereas expression of the endogenous RecA-family SSB (rSSB) increased recombinant yield by 5-fold, highlighting functional conservation. Furthermore, SSB proteins from heterologous hosts failed to enhance recombination efficiency. Using the optimized system, we successfully knocked out ten distinct genes, including virulence-associated loci, with editing accuracy exceeding 85%. Phenotypic analysis revealed that luxR, but not the other tested genes, contributes to biofilm formation. Virulence evaluation results showed that aroA, fur, and hfq are critical virulence-associated factors. Collectively, this streamlined recombineering system provides a simple, rapid, and efficient genetic tool for Edwardsiella, supporting mechanistic studies of virulence and the development of live attenuated vaccine candidates.

Edwardsiella piscicida↗

PubMed2026

Association of IL-10 promoter and IL-12 gene polymorphisms with the risk of symptomatic Helicobacter pylori infection.

BACKGROUND: The host's immune response to Helicobacter pylori (H. pylori) infection is largely determined by its cytokine profile. Genetic variations within crucial immunomodulatory genes, including those for interleukin-10 (IL-10) and interleukin-12 (IL-12), are thought to influence an individual's vulnerability to the infection and its clinical consequences by modifying cytokine production. Nonetheless, research data derived from diverse human populations continue to show inconsistent results. AIM: This case-control analysis sought to examine a potential link between symptomatic H. pylori infection susceptibility in an Iranian population and specific genetic variants in the IL-10 (-1082G > A, -819 C > T) and IL-12 (+ 1188 A > C) genes. METHODS: In this investigation, 68 individuals with confirmed symptomatic H. pylori infection diagnosed by a positive rapid urease test and elevated anti-H. pylori IgG levels exceeding 90 ng/ml via ELISA were enrolled alongside 68 healthy controls. The control group was carefully matched to the patient group based on age, sex, and ethnic background. Genotyping for the IL-10 (-1082G > A, -819 C > T) and IL-12 (+ 1188 A > C) polymorphisms was conducted using the Amplification Refractory Mutation System-PCR (ARMS-PCR) method. To evaluate associations, the distribution of genotypes and alleles between the groups was contrasted using logistic regression, applying additive, dominant, and recessive inheritance models. The strength of any association was expressed as odds ratios (ORs) accompanied by 95% confidence intervals (CIs). RESULTS: The analysis revealed no statistically significant correlations linking the investigated IL-10 and IL-12 gene variants to an increased predisposition for H. pylori infection. A notable methodological observation was the deviation from Hardy-Weinberg equilibrium (HWE) across all studied polymorphisms in the control group. Regarding the IL-10 -1082G > A locus, the AA genotype was associated with a marginally elevated risk estimate; however, this finding was not statistically significant (OR = 3.45, 95% CI: 0.29-41.36; p = 0.327). Likewise, for the IL-12 + 1188 A > C polymorphism, the CC genotype, while more prevalent in the patient cohort, also demonstrated no significant association with infection risk (OR = 1.43, 95% CI: 0.42-4.87; p = 0.567). CONCLUSION: This investigation did not establish a significant link between the specific IL-10 and IL-12 gene variants analyzed and susceptibility to symptomatic H. pylori infection in the studied population. Although minor genetic associations were noted, they lacked statistical significance. Future research with larger sample sizes is required to validate these results and to investigate additional genetic determinants that may affect infection risk.

Humans↗

PubMed2026

Utilisation and Perceived Value of Genetic Counsellors Within US Haemophilia Treatment Centres.

INTRODUCTION: Rapid advancement of molecular genetics has transformed the diagnosis, treatment, and management of individuals with hereditary bleeding disorders. To provide effective, up-to-date genetic counselling, navigate the complexity of these conditions, and select appropriate molecular testing, genetics expertise is required. AIM: This study assessed the provision of genetic counselling services, involvement of genetic counsellors (GCs), and the perceived value of GCs within haemophilia treatment centres (HTCs) in the United States. METHODS: A survey was emailed to 396 HTC providers. Of these, 115 responses were received, representing 68 of 149 US HTCs (45.6% HTC participation rate). Responses were stratified by level of GC engagement. RESULTS: Although GCs have extensive training in genetics, genomics and counselling skills, nearly one-third of respondents (34.9%, n = 38) reported that a GC is not involved with the HTC nor are referrals made. Almost all GC-engaged respondents (98%, n = 22) and GC-referral respondents (95%, n = 20) agreed that 'GCs have a unique skill set that is highly valuable to an HTC clinic' compared to only 62% (n = 20) of non-GC-engaged respondents (p = 0.001). Additionally, respondents noted positive implications of integrating a GC within their HTCs, stating that GCs are 'ideal for optimal patient care'. CONCLUSION: These results highlight the value of a GC within an HTC. This signifies the need to reassess the role of GCs among HTCs to reduce inconsistencies in provision of genetic counselling and increase healthcare equity.

Humans↗

PubMed2026

Rapid and repeated evolution of increased competitive ability in a global invader.

Rapid adaptive evolution can increase the competitive ability of invasive species in their non-native ranges. However, whether this increase is a general response and what drives it remain uncertain because the evidence is largely based on studies with limited sampling, inadequate consideration of population co-ancestry, and oversimplified estimates of competitive ability. We conduct a large-scale glasshouse experiment testing the effects of competition and drought on 100 native and 165 non-native populations of Erigeron canadensis, all genotyped to account for co-ancestry. Plants from non-native populations are significantly more competitive against other species than the conspecifics from native populations under both mesic and dry conditions. Genetic clustering indicates that the rapid evolution of competitive ability occurs independently in two out of four clusters in the non-native range. This advantage is present only during interspecific interactions and is absent during intraspecific competition. Repeated evolution of increased competitive ability suggests that adaptation following introduction can reshape species interactions and promote invasion success, even under future drought conditions, highlighting the importance of rapid evolution in determining the ecological impacts of invasive plants.

Biological Evolution↗

PubMed2025

Genomic testing for RET in the clinic: UK and global perspective.

RET is a key oncogene in neuroendocrine cancer. Pathogenic germline variants lead to multiple different phenotypes, including multiple endocrine neoplasia type 2, medullary thyroid cancer (MTC), Hirschsprung disease and kidney malformations. Pathogenic somatic variants are also associated with MTC, and RET rearrangements are observed in papillary thyroid cancer, non-small cell lung cancer and pan-cancer syndromes. Testing for both germline and somatic variants is now feasible in everyday clinical practice, and their identification has important clinical consequences, both for affected individuals and their families. This mini-review will discuss current germline and somatic testing strategies in the UK and worldwide, as well as reporting and test outcomes (including variants of uncertain significance or incidental findings). It will explore actions following identification of a pathogenic germline variant, including predictive, reproductive and childhood testing, and somatic testing of RET variants in solid tumours informing personalised cancer treatment. Finally, it will discuss the challenge of delivering rapid and equitable access to genomic testing to ensure that all individuals can benefit promptly and appropriately to improve clinical outcomes.

Humans↗

PubMed2026

Discovering common and population-specific QTLs for leaf rust resistance in different Barley populations.

Multi-population GWAS lead to identification of common and population-specific QTLs for leaf rust resistance in barley. Genome-wide association studies (GWAS) are a powerful tool for detecting genetic markers associated with traits of interest. However, these studies are typically restricted to a single population, and transferability of identified marker effects across populations is challenged by population differences in linkage, allele frequencies, epistatic effects, and environmental context. When comparing GWAS results between populations, a lack of overlapping signals is often interpreted as a lack of common quantitative trait loci (QTLs), although such discrepancies may result from differences in statistical power to detect signals. In barley (Hordeum vulgare L.), where genetic leaf rust resistance is rapidly overcome by evolving pathogens, identification of cross-population robust and potentially transferable resistance loci is a key task. Here, we present a mixed model approach for multi-population GWAS that estimates correlated marker effects in multiple populations and use this to test for significant effects across and within populations. Applying this model to four barley breeding populations revealed both common and population-specific QTL effects for leaf rust resistance, including loci colocalizing with known Rph genes and novel regions with plausible candidate genes. Multi-population GWAS increased power, revealing signals not detected by GWAS within populations. We categorized the reported QTLs into three groups based on marker-associated allele effects: (1) consistent effect direction across populations, (2) differing effect direction across populations, and (3) present in a single population. The study highlights the transferability and limitations of leaf rust resistance QTLs across different barley populations and provides a general statistical framework to support robust marker-assisted selection across populations.

Quantitative Trait Loci↗

PubMed2025

Impeding pathways of intrinsic resistance in Escherichia coli confers antibiotic sensitization and resistance proofing.

Pathways of intrinsic resistance in bacteria are promising targets for novel antibiotics and resistance breakers. Here, we used a genome-wide screen to identify single gene knockouts of Escherichia coli that were hypersusceptible to trimethoprim and chloramphenicol, two chemically diverse broad-spectrum antibiotics. Among the hits from our screen, knockouts of acrB, an efflux pump, and rfaG or lpxM, both involved in cell envelope biogenesis, were hypersensitive to multiple antimicrobials and could sensitize genetically resistant E. coli strains to antibiotics. Using experimental evolution under trimethoprim pressure, we show that high drug selection regimes drove these knockouts to extinction more frequently than wild type. Among them, ΔacrB was most compromised in its ability to evolve resistance, establishing it as a promising target for "resistance proofing." At a sub-inhibitory trimethoprim concentration, however, all three knockouts adapted to the antibiotic and consequently recovered from hypersensitivity, albeit to different extents. This recovery was driven by mutations in drug-specific resistance pathways, rather than compensatory evolution, frequently involving upregulation of the drug target. Notably, resistance-conferring mutations could by-pass defects in cell wall biosynthesis more effectively than efflux even though resistant mutations did not directly engage either pathway. Since inhibiting drug-efflux emerged as a better strategy, we tested the ability of chlorpromazine, an efflux pump inhibitor (EPI), to resistance proof E. coli against trimethoprim. While qualitatively similar in the short term, genetic and pharmacological inhibition differed dramatically on an evolutionary time scale due to evolution of resistance to the EPI. Further, adaptation to the EPI-antibiotic pair also led to multidrug adaptation. The lack of concordance between genetic and pharmacological inhibition revealed a crucial lacuna in our understanding of the mutational repertoires that facilitate adaptation to antibiotics in bacteria. We propose that while intrinsic resistance mechanisms are effective targets for antibiotic sensitization, rapid evolutionary recovery may significantly limit their utility.

Escherichia coli↗