Genetic Information Research Articles

The HMG-box module in FACT is critical for suppressing epigenetic variegation of heterochromatin in fission yeast.

Chromatin condensation state is the key for retrieving genetic information. High-mobility group protein (HMG) proteins exhibit DNA-binding and bending activities, playing an important role in the regulation of chromatin structure. We have shown that nucleosomes tightly packaged into heterochromatin undergo considerable dynamic histone H2A-H2B maintenance via the direct interaction between HP1/Swi6 and facilitate chromatin transcription (FACT), which is composed of the Spt16/Pob3 heterodimer and Nhp6. In this study, we analyzed the role of Nhp6, an HMG box protein, in the FACT at heterochromatin. Pob3 mutant strains showed derepressed heterochromatin-dependent gene silencing, whereas Nhp6 mutant strains did not show significant defects in chromatin regulation or gene expression, suggesting that these two modules play different roles in chromatin regulation. We expressed a protein fusing Nhp6 to the C-terminus of Pob3, which mimics the multicellular FACT component Ssrp1. The chromatin-binding activity of FACT increased with the number of Nhp6 fused to Pob3, and the heterochromatin formation rate was promoted more strongly. Furthermore, we demonstrated that this promotion of heterochromatinization inhibited the heterochromatic variegation caused by epe1+ disruption. Heterochromatic variegation can be observed in a variety of regulatory steps; however, when it is caused by fluctuations in chromatin arrangement, it can be eliminated through the strong recruitment of the FACT complex.

The game between artificial management and natural environment determines the adaptive strategies of leaf morphogenesis in Sabina chinensis.

Sabina chinensis is a typically heteromorphic leaf evergreen tree worldwide with both ornamental and ecological value. However, the shaping mechanism of heteromorphic leaves of Sabina chinensis and its adaptability to environment are important factors determining its morphology. The morphological change of S. chinensis which under different habitats (arbor around) and treatments (light, pruning and nutrients) was investigated. Our findings suggested that the prickle leaves proportion was associated with low light intensity and soil nutrient scarcity. Stems and leaves are pruned together to form clusters of large prickle leaves, while only pruning leaves often form alternately growing small prickle leaves and scale leaves, and the length of the prickle leaves is between 0.5cm to 1cm. The gene expression of prickle leaves is higher than that of scale leaves that under adverse environmental conditions, and the gene expression correlations of small prickle leaf and scale leaf were the highest. Homologous and heterologous mutants of gene structure in prickle leaves were larger than those in scale leaves. KEGG pathway showed that phenylpropanone and flavonoid biosynthesis were common enrichment pathways, and the enrichment genes were mainly related to metabolism, genetic information processing and organismal systems. Therefore, we concluded that the occurrence of the heteromorphic leaf phenomenon was related to the changes in photosynthesis, mechanical damage and nutrient supplementation. The organic matter in the S. chinensis prickle leaves was reduced under environmental stresses, and it will be allocated to the expression to the prickle leaf or protective cuticles formation.

Genetic Relationships of Cultivated Flax and Its Wild Progenitor as Revealed by 454 Pyrosequencing, Sanger Resequencing and Microsatellite Data

Flax (Linum usitatissimum L.), as the earliest oil and fiber crop, is a model plant for genetic inferences of plant domestication processes involving multiple domestication events. However, a puzzle has emerged from several genetic studies, as dehiscent cultivated flax is genetically more related to its progenitor pale flax (L. bienne Mill.), and winter cultivated flax is well mixed with oil or fiber cultivated flax, while capsular dehiscence and winter hardiness are the major characteristics of pale flax. For this, a comparative analysis was conducted with 16 Linum samples representing pale flax and four domestication groups of cultivated flax (oil, fiber, winter, and dehiscent) using 454 pyrosequencing, Sanger resequencing and microsatellite data. It was found that the genomic sampling of genetic variants from the three applied methods yielded similar genetic information on pale flax and four groups of cultivated flax. The revealed genetic relationships did not show significant departures from the previous findings, but instead supported an early, independent domestication of a primitive flax lineage for oil use, followed by a subsequent flax domestication process with multiple domestication events for capsular dehiscence, oil, fiber and winter hardiness. Domestication on capsular dehiscence occurred earlier than domestication on winter hardiness. Domestication on winter hardiness was more complicated than domestication on capsular dehiscence.

Past and future climate effects on population structure and diversity of North Pacific surfgrasses

AbstractAimUnderstanding the impacts of past and future climate change on genetic diversity and structure is a current major research gap. We ask whether past range shifts explain the observed genetic diversity of surfgrass species and if future climate change projections anticipate genetic diversity losses. Our study aims to identify regions of long‐term climate suitability with higher and unique seagrass genetic diversity and predict future impacts of climate change on them.LocationNortheast Pacific.Time PeriodAnalyses considered a timeframe from the Last Glacial Maximum (LGM; 20 kybp) until one Representative Concentration Pathway (RCP) scenario of future climate changes (RCP 8.5; 2100).Major Taxa StudiedTwo seagrass species belonging to the genus Phyllospadix.MethodsWe estimated population genetic diversity and structure using 11 polymorphic microsatellite markers. We predicted the distribution of the species for the present, LGM, and near future (RCP 8.5, no climate mitigation) using Species Distribution Models (SDMs).ResultsSDMs revealed southward range shifts during the LGM and potential poleward expansions in the future. Genetic diversity of Phyllospadix torreyi decreases from north to south, but in Phyllospadix scouleri the trend is variable. Phyllospadix scouleri displays signals of genome admixture at the southernmost and northernmost edges of its distribution.Main ConclusionsThe genetic patterns observed in the present reveal the influence of climate‐driven range shifts in the past and suggest further consequences of climate change in the future, with potential loss of unique gene pools. This study also shows that investigating climate links to present genetic information at multiple timescales can establish a historical context for analyses of the future evolutionary history of populations.

Small extracellular vesicles as a novel liquid biopsy approach for glioblastoma.

2073 Background: Glioblastoma (GBM) remains the most common and aggressive primary malignant brain tumor, and afflicted patients have limited options and poor overall survival. Diagnosis, prognosis, and assessment of treatment effectiveness is hampered by the absence of readily available sensitive, tumor specific, non-invasive blood-based assays which could be followed serially. Small extracellular vesicles (sEV) are nano-sized (≤200 nm) membrane bound bodies secreted by all cells, encapsulating cargo reflective of their parent cells. sEV have emerged as promising molecular indicator of a disease condition. Here, we report the feasibility of isolating glioma specific sEV (sEVglioma) from the plasma and characterizing those for GBM specific molecular biomarkers. Methods: Plasma samples were collected from patients (n=31) diagnosed with adult gliomas (including grade 3 and 4 GBM, grade 2 and 3 astrocytoma) and healthy individuals (n=9). Total sEV (TE) population was isolated from plasma by a modified precipitation (ExoQuick) method. Next, sEVglioma were isolated from the TE by an immunoprecipitation approach employing specific surface markers targeting cellular origin of gliomas, including astrocyte (GLAST and EAAT2), oligodendrocyte precursor cell (OSP and MOG), and neural stem cell (CD133). sEVglioma were characterized for size and concentration by nanoparticle tracking analyses; surface expression of glioma specific biomarkers by nano-flow cytometry and confocal microscopy; and the expression of a panel of specific miRNAs by RT-PCR. Lastly, sEVglioma were assessed by digital PCR for IDH1 status (wild type or mutated). Results: The average size of isolated sEVglioma was less than 200nm. Importantly, compared to TE, sEVglioma showed significant enrichment for glioma specific biomarkers such as ephrin type-A receptor 2 (14.7-fold), tenascin C (22.7-fold), and glial fibrillary acidic protein (8.4-fold) by nano-flow cytometry. Similarly, sEVglioma, but not TE, demonstrated high expression of EGFRvIII (3.6-fold), a known biomarker for GBM. These results were confirmed by confocal microscopy. Interestingly, expression of specific miRNAs (miR-9a-5p, miR-16-5p, miR-21-5p) in sEVglioma was higher in glioma patients with shorter survival (<12 months) compared to patients with longer survival (>20 months). Lastly, we successfully detected the existence of wild type IDH1 and absence of mutated IDH1 R132H in sEVglioma from GBM patients. This approach was validated in sEV isolated from the conditioned media of IDH1-wild type GBM cell lines (A172 and T98G) and a IDH1-mutated cell line (BT54). Conclusions: We present a novel approach to isolate sEVglioma from blood that could serve as a liquid biopsy, offering valuable molecular and genetic information. This approach promises early detection, potential to distinguish pseudo-progression, and assessment of treatment effectiveness with remarkable precision.

From Zero to Hero: The Cyanide-Free Formation of Amino Acids and Amides from Acetylene, Ammonia and Carbon Monoxide in Aqueous Environments in a Simulated Hadean Scenario.

Amino acids are one of the most important building blocks of life. During the biochemical process of translation, cells sequentially connect amino acids via amide bonds to synthesize proteins, using the genetic information in messenger RNA (mRNA) as a template. From a prebiotic perspective (i.e., without enzymatic catalysis), joining amino acids to peptides via amide bonds is difficult due to the highly endergonic nature of the condensation reaction. We show here that amides can be formed in reactions catalyzed by the transition metal sulfides from acetylene, carbon monoxide and ammonia under aqueous conditions. Some α- and β-amino acids were also formed under the same conditions, demonstrating an alternative cyanide-free path for the formation of amino acids in prebiotic environments. Experiments performed with stable isotope labeled precursors, like 15NH4Cl and 13C-acetylene, enabled the accurate mass spectroscopic identification of the products formed from the starting materials and their composition. Reactions catalyzed using the transition metal sulfides seem to offer a promising alternative pathway for the formation of amides and amino acids in prebiotic environments, bypassing the challenges posed by the highly endergonic condensation reaction. These findings shed light on the potential mechanisms by which the building blocks of life could have originated on early Earth.

Precision oncology and AI: The ACMA system for personalized treatment matching using real-world data.

e23134 Background: Precision oncology promises tailored cancer treatments, yet current methods often overlook individual patient variability. The AI-powered Case Matching Assistant (ACMA) system addresses this by utilizing real-world data (RWD) from over 100,000 clinical cases to personalize treatment strategies, considering genetic profiles, cancer types, treatment stages, and drug interactions. Methods: ACMA enhances the Large Language Model (LLM) with oncology-specific pretraining that encompasses both molecular and clinical data, ensuring a holistic understanding of patient profiles. It employs cosine similarity for multi-faceted case comparisons, integrating genetic, biomarker, and vital clinical information. Context-aware learning prompts fine-tune the LLM, generating recommendations that reflect the full spectrum of patient-specific data, from genetic variations to clinical histories and treatment responses, facilitating truly personalized treatment pathways. Results: Preliminary results show ACMA's tailored recommendations improve patient outcomes, with increased median survival rates and cost-effective treatment options. The system's 90% relevance match for clinical trial enrollment also expands access to novel therapies. In the absence of a standard treatment protocol for BRCA germline mutations in advanced lung cancer, ACMA provides crucial insights. For instance, a 36-year-old female with BRCA1 c.527del mutation achieved complete remission with a PFS of 38 months after a combination therapy trial. A 56-year-old male with a BRCA2 S1722Yfs*mutation saw partial remission and over 6 months PFS with olaparib. Another male patient, a smoker with concurrent BRCA2 G1712X and TP53 mutations, experienced partial remission following apatinib therapy. ACMA analyzed treatment data from similar genetic profiles and identified a targeted therapy that had shown efficacy in comparable cases. The oncologist used this information as a reference to adjust the treatment plan, resulting in a positive clinical outcome for the patient. This example underscores the potential of ACMA to provide actionable insights for personalized cancer care. Conclusions: Surpassing traditional single-feature matching, ACMA rapidly aligns multi-dimensional characteristics such as cancer type, disease stage, molecular data, and treatment phases. It customizes the interplay of these features with medical logic, delivering tailored outputs through the LLM. This approach offers an economical, convenient, and timely solution, setting a new benchmark in personalized oncology and establishing ACMA as a leader in the field. This distinctive advantage not only enhances patient outcomes but also establishes a formidable barrier to entry for competitors, solidifying ACMA's position at the forefront of oncology practice.

Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction

Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82–0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.

Lessons learned in migrating from one commercial genetics decision-support tool to another: Assessment of data integrity and utilization readiness.

e23232 Background: Rapid advancements in health information technology have greatly influenced how clinicians engage with patient health data. In the context of clinical genetics, the electronic health record (EHR) often contains a wide array of data to identify patients at elevated risk for hereditary cancer syndromes. However, these data often exist in multiple forms and disparate locations, which in the presence of numerous commercial EHR solutions, results in significant variations in how institutions codify genetic data. Furthermore, within an institution, there is often internal pressure to migrate from one support tool to another, necessitating a focus on data integrity during such a transition. Methods: Fred Hutchinson Cancer Center (Fred Hutch) is a large academic cancer care center associated with the University of Washington. Between July and December 2023, the Fred Hutch Clinical Cancer Genetics and Genetic Counseling Service migrated their family history database from commercial pedigree software, Progeny, to another commercial pedigree and decision-support tool, CancerIQ. Following completion of the data migration on more than 13,000 patient records, study team planned to review a total of 500 randomly selected patient charts in both support tools. Each chart was reviewed to determine: (1) the presence of genetic intake information, (2) the presence and results of genetic testing, if available, and (3) whether the patient met National Comprehensive Cancer Network (NCCN) criteria for testing. A chart was noted to be concordant between the two support tools if there was agreement in all three of the above. Results: So far, a total of 240 patient charts were reviewed between the two support tools. Of these, 226 (94.2%) were noted to be fully concordant. Of the 14 charts that were noted to be discordant, the distribution of the discordant data was: 5 charts differed on whether genetic testing had been ordered, 5 charts differed on the results of the testing (often omitting one or more variants), and 4 differed on whether the patient met NCCN criteria for testing. Conclusions: At our institution, there was high data integrity following migration from one commercial and pedigree-generating software solution to another. While these results can ease clinician concerns following such support tools transitions, it also highlights areas for improvement in how family and patient genetic data is recorded.

Concurrent Infection with Clade 2.3.4.4b Highly Pathogenic Avian Influenza H5N6 and H5N1 Viruses, South Korea, 2023.

Highly pathogenic avian influenza H5N6 and H5N1 viruses of clade 2.3.4.4b were simultaneously introduced into South Korea at the end of 2023. An outbreak at a broiler duck farm consisted of concurrent infection by both viruses. Sharing genetic information and international surveillance of such viruses in wild birds and poultry is critical.

Predicting gene disease associations with knowledge graph embeddings for diseases with curtailed information.

Knowledge graph embeddings (KGE) are a powerful technique used in the biomedical domain to represent biological knowledge in a low dimensional space. However, a deep understanding of these methods is still missing, and, in particular, regarding their applications to prioritize genes associated with complex diseases with reduced genetic information. In this contribution, we built a knowledge graph (KG) by integrating heterogeneous biomedical data and generated KGE by implementing state-of-the-art methods, and two novel algorithms: Dlemb and BioKG2vec. Extensive testing of the embeddings with unsupervised clustering and supervised methods showed that KGE can be successfully implemented to predict genes associated with diseases and that our novel approaches outperform most existing algorithms in both scenarios. Our findings underscore the significance of data quality, preprocessing, and integration in achieving accurate predictions. Additionally, we applied KGE to predict genes linked to Intervertebral Disc Degeneration (IDD) and illustrated that functions pertinent to the disease are enriched within the prioritized gene set.

G-quadruplex propensity in H. neanderthalensis, H. sapiens and Denisovans mitochondrial genomes.

Current methods of processing archaeological samples combined with advances in sequencing methods lead to disclosure of a large part of H. neanderthalensis and Denisovans genetic information. It is hardly surprising that the genome variability between modern humans, Denisovans and H. neanderthalensis is relatively limited. Genomic studies may provide insight on the metabolism of extinct human species or lineages. Detailed analysis of G-quadruplex sequences in H. neanderthalensis and Denisovans mitochondrial DNA showed us interesting features. Relatively similar patterns in mitochondrial DNA are found compared to modern humans, with one notable exception for H. neanderthalensis. An interesting difference between H. neanderthalensis and H. sapiens corresponds to a motif found in the D-loop region of mtDNA, which is responsible for mitochondrial DNA replication. This area is directly responsible for the number of mitochondria and consequently for the efficient energy metabolism of cell. H. neanderthalensis harbor a long uninterrupted run of guanines in this region, which may cause problems for replication, in contrast with H. sapiens, for which this run is generally shorter and interrupted. One may propose that the predominant H. sapiens motif provided a selective advantage for modern humans regarding mtDNA replication and function.

Mendelian randomization: causal inference leveraging genetic data.

Mendelian randomization (MR) leverages genetic information to examine the causal relationship between phenotypes allowing for the presence of unmeasured confounders. MR has been widely applied to unresolved questions in epidemiology, making use of summary statistics from genome-wide association studies on an increasing number of human traits. However, an understanding of essential concepts is necessary for the appropriate application and interpretation of MR. This review aims to provide a non-technical overview of MR and demonstrate its relevance to psychiatric research. We begin with the origins of MR and the reasons for its recent expansion, followed by an overview of its statistical methodology. We then describe the limitations of MR, and how these are being addressed by recent methodological advances. We showcase the practical use of MR in psychiatry through three illustrative examples - the connection between cannabis use and psychosis, the link between intelligence and schizophrenia, and the search for modifiable risk factors for depression. The review concludes with a discussion of the prospects of MR, focusing on the integration of multi-omics data and its extension to delineating complex causal networks.

Diaminopurine in Nonenzymatic RNA Template Copying.

In the RNA World before the emergence of an RNA polymerase, nonenzymatic template copying would have been essential for the transmission of genetic information. However, the products of chemical copying with the canonical nucleotides (A, U, C, and G) are heavily biased toward the incorporation of G and C, which form a more stable base pair than A and U. We therefore asked whether replacing adenine (A) with diaminopurine (D) might lead to more efficient and less biased nonenzymatic template copying by making a stronger version of the A:U pair. As expected, primer extension substrates containing D bound to U in the template more tightly than substrates containing A. However, primer extension with D exhibited elevated reaction rates on a C template, leading to concerns about fidelity. Our crystallographic studies revealed the nature of the D:C mismatch by showing that D can form a wobble-type base pair with C. We then asked whether competition with G would decrease the mismatched primer extension. We performed nonenzymatic primer extension with all four activated nucleotides on randomized RNA templates containing all four letters and used deep sequencing to analyze the products. We found that the DUCG genetic system exhibited a more even product distribution and a lower mismatch frequency than the canonical AUCG system. Furthermore, primer extension is greatly reduced following all mismatches, including the D:C mismatch. Our study suggests that D deserves further attention for its possible role in the RNA World and as a potentially useful component of artificial nonenzymatic RNA replication systems.

RNA Analysis in Forensic Molecular Biology.

Different types of RNA take on multiple crucial functions in living cells and tissues. Messenger RNA (mRNA) is a temporary molecular carrier of genetic information. Analysis of the composition of all mRNA contained in a cell at a given moment, the so-called transcriptome, enables the determination of the type of cell and its condition, e.g., in pathologically altered states. This review is based on pertinent publications retrieved by a selective literature search. The analysis of differential gene expression has already been used in forensic molecular biology to determine the type of tissue contained in biological specimens. It is also being used in criminal investigations to determine the composition of mixed traces of various bodily fluids and/or organ tissues. The method is limited by degradation of the mRNA molecules through environmental influences. The use of newly developed molecular biological methods such as massive parallel sequencing can expand the information obtainable by this investigative method. Current research also addresses the forensic potential of deriving relevant information about the crime-e.g., its timing, or the condition of the involved persons-from the totality of mRNA species present in the specimens. Forensic RNA analysis can yield a great deal of relevant information. It is likely to be applicable in a much wider variety of forensic situations in the near future.

Comparative analysis of genetic variants in pleural fluids and solid tissue biopsies of pleural mesothelioma patients: Implications for molecular heterogeneity assessment

ObjectivesThis study aims to determine whether the sequencing of DNA extracted from pleural fluids (PFs) of Pleural Mesothelioma (PM) patients accurately represents the genetic information obtained from the solid tissue counterpart biopsies with particular attention to the identification of single nucleotide variants (SNVs). Materials and methodsSingle pleural biopsy, PFs, and blood were collected from PM patients. DNA was extracted from these samples and then subjected to Whole-Exome Sequencing. ResultsA higher number of SNVs was identified in PFs than in solid tissue biopsies (STBs). Most SNVs were detected in PFs samples but not in STBs samples, while only a few SNVs were detected in STBs samples but not in PFs samples. ConclusionThe current findings support the notion that PFs might offer a more robust depiction of cancer's molecular diversity. Nonetheless, the current outcomes challenge the assertion that liquid biopsies can encompass the entirety of intra-patient variations. Indeed, a subset of potential cancer-driver SNVs was exclusively identified in STBs. However, relying solely on STBs would have precluded the detection of significant SNVs that were exclusively present in PFs. This implies that while PFs serve as a valuable complement to STBs, they do not supplant them.

Genome-wide identification and expression analysis of the SPL transcription factor family and its response to abiotic stress in Pisum sativum L

Squamous promoter binding protein-like (SPL) genes encode plant-specific transcription factors (TFs) that play essential roles in modulating plant growth, development, and stress response. Pea (Pisum sativum L.) is a coarse grain crop of great importance in food production, biodiversity conservation and molecular genetic research, providing genetic information and nutritional resources for improving agricultural production and promoting human health. However, only limited researches on the structure and functions of SPL genes exist in pea (PsSPLs). In this study, we identified 22 PsSPLs and conducted a genome-wide analysis of their physical characteristics, chromosome distribution, gene structure, phylogenetic evolution and gene expression patterns. As a result, the PsSPLs were unevenly distributed on the seven chromosomes of pea and harbored the SBP domain, which is composed of approximately 76 amino acid residues. The phylogenetic analysis revealed that the PsSPLs clustered into eight subfamilies and showed high homology with SPL genes in soybean. Further analysis showed the presence of segmental duplications in the PsSPLs. The expression patterns of 22 PsSPLs at different tissues, developmental stages and under various stimulus conditions were evaluated by qRT-PCR method. It was found that the expression patterns of PsSPLs from the same subfamily were similar in different tissues, the transcripts of most PsSPLs reached the maximum peak value at 14 days after anthesis in the pod. Abiotic stresses can cause significantly up-regulated PsSPL19 expression with spatiotemporal specificity, in addition, four plant hormones can cause the up-regulated expression of most PsSPLs including PsSPL19 in a time-dependent manner. Therefore, PsSPL19 could be a key candidate gene for signal transduction during pea growth and development, pod formation, abiotic stress and plant hormone response. Our findings should provide insights for the elucidating of development regulation mechanism and breeding for resistance to abiotic stress pea.

Family communication of cancer genetic test results in an ethnically diverse population: a qualitative exploration of more than 200 patients.

Previous research on family communication of cancer genetic test results has primarily focused on non-Hispanic White patients with high-risk pathogenic variants (PV). There are limited data on patient communication of moderate-risk PVs, variants of uncertain significance (VUS), and negative results. This qualitative study examined communication of positive, negative, and VUS hereditary cancer multi-gene panel (MGP) results in an ethnically and socioeconomically diverse population. As part of a multicenter, prospective cohort study of 2000 patients who underwent MGP testing at three hospitals in California, USA, free-text written survey responses to the question: "Feel free to share any thoughts or experiences with discussing genetic test results with others" were collected from participant questionnaires administered at 3 and 12-months post results disclosure. Content and thematic analyses were performed using a theory-driven analysis, Theory of Planned Behavior (TPB), on 256 responses from 214 respondents. Respondents with high perceived utility of sharing genetic test results often reported positive attitudes towards sharing test results and direct encouragement for genetic testing of others. Respondents with high self-efficacy in the sharing process were likely to report high perceived utility of sharing, whereas patients with low self-efficacy more often had VUS results and were more likely to report uncertainty about sharing. Consistent with TPB, our findings suggest that clinician reinforcement of the utility of genetic testing may increase intent for patients to communicate genetic information. Our findings suggest that clinicians should focus on strategies to improve patient understanding of VUS results.

Comparative chloroplast genomics and phylogenetic analysis of Oreomecon nudicaulis (Papaveraceae)

Oreomecon nudicaulis, commonly known as mountain poppy, is a significant perennial herb. In 2022, the species O. nudicaulis, which was previously classified under the genus Papaver, was reclassified within the genus Oreomecon. Nevertheless, the phylogenetic status and chloroplast genome within the genus Oreomecon have not yet been reported. This study elucidates the chloroplast genome sequence and structural features of O. nudicaulis and explores its evolutionary relationships within Papaveraceae. Using Illumina sequencing technology, the chloroplast genome of O. nudicaulis was sequenced, assembled, and annotated. The results indicate that the chloroplast genome of O. nudicaulis exhibits a typical circular quadripartite structure. The chloroplast genome is 153,903 bp in length, with a GC content of 38.87%, containing 84 protein-coding genes, 8 rRNA genes, 38 tRNA genes, and 2 pseudogenes. The genome encodes 25,815 codons, with leucine (Leu) being the most abundant codon, and the most frequently used codon is AUU. Additionally, 129 microsatellite markers were identified, with mononucleotide repeats being the most abundant (53.49%). Our phylogenetic analysis revealed that O. nudicaulis has a relatively close relationship with the genus Meconopsis within the Papaveraceae family. The phylogenetic analysis supported the taxonomic status of O. nudicaulis, as it did not form a clade with other Papaver species, consistent with the revised taxonomy of Papaveraceae. This is the first report of a phylogenomic study of the complete chloroplast genome in the genus Oreomecon, which is a significant genus worldwide. This analysis of the O. nudicaulis chloroplast genome provides a theoretical basis for research on genetic diversity, molecular marker development, and species identification, enriching genetic information and supporting the evolutionary relationships among Papaveraceae.

Prevalence of Leber hereditary optic neuropathy in the Community of Madrid (Spain), estimation with a capture-recapture method

BackgroundLeber hereditary optic neuropathy (LHON) typically presents in young adults as bilateral painless subacute visual loss. Prevalence data are scarce. The aim of this study was to examine the validity of different ascertainment sources used in population-based rare diseases registries to detect cases, and to explore the impact of a capture-recapture method in the estimation of the prevalence of LHON in the Autonomous Community of Madrid (ACM) in 2022.MethodsDescriptive cross-sectional population-based study. Potential LHON cases were detected by automatic capture from the healthcare information sources usually explored for the Regional Registry for Rare Diseases (SIERMA). Ophthalmologists provided data from their clinical registry. Positive predictive values (PPV) and sensitivity with 95% confidence intervals (CI) were estimated. Global and by sex prevalences were calculated with confimed cases and with those estimated by the capture-recapture method.ResultsA total of 102 potential LHON cases were captured from healthcare information sources, 25 of them (24.5%) finally were confirmed after revision, with an overall PPV of 24.5% (95%CI 17.2–33.7). By source, the electronic clinical records of primary care had the highest PPV (51.2, 95%CI 36.7–65.4). The ophthalmologists clinical registry provided 22 cases, 12 of them not detected in the automatic capture sources. The clinical registry reached a sensitivity of 59.5% (95%CI 43.5–73.6) and the combination of automatic capture sources reached a 67.6% (95%CI: 51.5–80.4). The total confirmed cases were 37, with a mean age of 48.9 years, and a men: women ratio of 2.4:1. Genetic information was recovered in 27 cases, with the m.3460 mutation being the most frequent (12 cases). The global prevalence was 0.55 cases/100,000 inhabitants (95%CI 0.40–0.75), and with the capture-recapture method reached 0.79 cases/100,000 (95%CI 0.60–1.03), a 43.6% higher, 1.15 cases/100,000 (95%CI 0.83–1.58) in men and 0.43 cases/100,000 (95%CI 0.26–0.70) in women.ConclusionsThe prevalence of LHON estimated in the ACM was lower than in other European countries. Population-based registries of rare diseases require the incorporation of confirmed cases provided by clinicians to asure the best completeness of data. The use of more specific coding for rare diseases in healthcare information systems would facilitate the detection of cases. Further epidemiologic studies are needed to assess potential factors that may influence the penetrance of LHON.