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TP53 pathogenic variants cause Li-Fraumeni syndrome (LFS), with some variants causing an attenuated phenotype. Herein, we describe the clinical phenotype and genetic characteristics of carriers of NM_000546.6 (TP53): c.541C > T, (p.Arg181Cys) treated at Hadassah Medical Center. We retrospectively examined our genetic databases to identify all carriers of TP53 p.Arg181Cys. We reached out to carriers and their relatives and collected clinical and demographic data, lifestyle factors, carcinogenic exposures as well as additional blood samples for genetic testing and whole exome sequencing. Between 2005 and 2022 a total of 2875 cancer patients underwent genetic testing using genetic panels, whole exome sequencing or targeted TP53 assays. A total of 30 cancer patients, all of Arab-Muslim descent, were found to be carriers of TP53 p.Arg181Cys, the majority from Jerusalem and Hebron, two of which were homozygous for the variant. Carriers were from 24 distinct families of them, 15 families (62.5%) met updated Chompret criteria for LFS. Median age of diagnosis was 35 years-old (range 1–69) with cancers characteristic of LFS (16 Breast cancer; 6 primary CNS tumors; 3 sarcomas) including 4 children with choroid plexus carcinoma, medulloblastoma, or glioblastoma. A total of 21 healthy carriers of TP53 p.Arg181Cys were identified at a median age of 39 years-old (range 2–54)—19 relatives and 2 additional pediatric non-cancer patients, in which the finding was incidental. We report a shared haplotype of 350kb among carriers, limited co-morbidities and low BMI in both cancer patients and healthy carriers. There were no demographic factors or carcinogenic exposures unique to carriers who developed malignancy. Upon exome analysis no other known pathogenic variants in cancer predisposing genes were identified. TP53 p.Arg181Cys is a founder pathogenic variant predominant to the Arab-Muslim population in Jerusalem and Hebron, causing attenuated-LFS. We suggest strict surveillance in established carriers and encourage referral to genetic testing for all cancer patients of Arab-Muslim descent in this region with LFS-associated malignancies as well as family members of established carriers. [ABSTRACT FROM AUTHOR]

Land managers, researchers, and regulators increasingly utilize environmental DNA (eDNA) techniques to monitor species richness, presence, and absence. In order to properly develop a biological assay for eDNA metabarcoding or quantitative PCR, scientists must be able to find not only reference sequences (previously identified sequences in a genomics database) that match their target taxa but also reference sequences that match non-target taxa. Determining which taxa have publicly available sequences in a time-efficient and accurate manner currently requires computational skills to search, manipulate, and parse multiple unconnected DNA sequence databases. Our team iteratively designed a Graphic User Interface (GUI) Shiny application called the Reference Sequence Browser (RSB) that provides users efficient and intuitive access to multiple genetic databases regardless of computer programming expertise. The application returns the number of publicly accessible barcode markers per organism in the NCBI Nucleotide, BOLD, or CALeDNA CRUX Metabarcoding Reference Databases. Depending on the database, we offer various search filters such as min and max sequence length or country of origin. Users can then download the FASTA/GenBank files from the RSB web tool, view statistics about the data, and explore results to determine details about the availability or absence of reference sequences. [ABSTRACT FROM AUTHOR]

SUMMARY The BonnMu resource is a transposon tagged mutant collection designed for functional genomics studies in maize. To expand this resource, we crossed an active Mutator (Mu) stock with dent (B73, Co125) and flint (DK105, EP1, and F7) germplasm, resulting in the generation of 8064 mutagenized BonnMu F2‐families. Sequencing of these Mu‐tagged families revealed 425 924 presumptive heritable Mu insertions affecting 36 612 (83%) of the 44 303 high‐confidence gene models of maize (B73v5). On average, we observed 12 Mu insertions per gene (425 924 total insertions/36 612 affected genes) and 53 insertions per BonnMu F2‐family (425 924 total insertions/8064 families). Mu insertions and photos of seedling phenotypes from segregating BonnMu F2‐families can be accessed through the Maize Genetics and Genomics Database (MaizeGDB). Downstream examination via the automated Mutant‐seq Workflow Utility (MuWU) identified 94% of the presumptive germinal insertion sites in genic regions and only a small fraction of 6% inserting in non‐coding intergenic sequences of the genome. Consistently, Mu insertions aligned with gene‐dense chromosomal arms. In total, 42% of all BonnMu insertions were located in the 5′ untranslated region of genes, corresponding to accessible chromatin. Furthermore, for 38% of the insertions (163 843 of 425 924 total insertions) Mu1, Mu8 and MuDR were confirmed to be the causal Mu elements. Our publicly accessible European BonnMu resource has archived insertions covering two major germplasm groups, thus facilitating both forward and reverse genetics studies. [ABSTRACT FROM AUTHOR]

Fish are considered objective indicators of environmental health and ecosystem stability. Establishing regional reference databases of mitochondrial genome sequences from local fish communities can significantly enhance fish monitoring using environmental DNA (eDNA) analysis. For non-native species, the eDNA technique provides early detection and rapid monitoring. It is also crucial to include fundamental genetic information for both native and non-native species in genetic databases. This study presents the complete mitochondrial genomes of 17 fish species inhabiting the Baiyangdian Basin, a national key wetland in China. The mitochondrial DNA of these fish was analyzed to investigate their characteristics, and their phylogeny was determined using maximum likelihood (ML) methods. Various analyses were performed, including the examination of nucleotide composition, evaluation of AT-skew and GC-skew, analysis of codon frequency, and determination of relative synonymous codon usage (RSCU) values, and assessment of selection pressure on protein-coding genes (PCGs). The analysis showed that all PCGs in all fish underwent purifying selection. Using Xenocyprididae as a representative, this study investigated the genetic selection tendencies of native and non-native fish species in the Baiyangdian Basin. Significant differences were found in five of the 13 PCGs: COI, COII, COIII, Cytb, and ATP8. Except for ATP8, the findings indicated that the genes of nonnative species underwent stronger purifying selection during evolution compared to native species. Additionally, comparing the population ω values of non-native species to those of native species showed that the Cytb and COIII genes exhibited greater differential purification selection than COI and COII. These differences may be the result of the evolution of non-native species to migrate and adapt to the Baiyangdian Basin, thereby affecting the evolution of related genes. [ABSTRACT FROM AUTHOR]

Background: Genomic medicine has transformed clinical genetics by utilizing high‐throughput sequencing technologies to analyze genetic variants associated with diseases. Accurate variant classification is crucial for diagnosis and treatment decisions, and various tools and software such as the Ion Reporter Software and the Illumina Nirvana Software often used in a clinical setting utilize information from the ClinVar database/archive to aid in variant interpretation. However, these existing annotation tools may lack access to the latest ClinVar data, necessitating manual variant inspection. Aims: To address this gap in developing a tool providing the latest ClinVar data for variant annotation in clinical and research settings. Materials and Methods: We introduce CANVAR, a Python‐based script that efficiently annotates variants identified from next‐generation sequencing in a clinical or research context, offering comprehensive information from the latest ClinVar database. Results: CANVAR provides accurate, up‐to‐date variant annotations, streamlining variant analysis. Discussion: The rise in genomic data requires accurate variant annotation for clinical decision‐making. Misclassification poses risks, and current tools may not always access the latest data, challenging variant interpretation. Conclusion: CANVAR contributes to enhancing variant annotation by offering comprehensive information from the latest ClinVar database for genetic variants identified through next‐generation sequencing. [ABSTRACT FROM AUTHOR]

Background: Investigative genetic genealogy (IGG) is a technique that involves uploading genotypes developed from perpetrator DNA left at a crime scene, or DNA from unidentified remains, to public genetic genealogy databases to identify genetic relatives and, through the creation of a family tree, the individual who was the source of the DNA. As policymakers demonstrate interest in regulating IGG, it is important to understand public perspectives on IGG to determine whether proposed policies are aligned with public attitudes. Methods: We conducted eight focus groups with members of the public (N = 72), sampled from four geographically diverse US regions, to explore general attitudes and perspectives regarding aspects of IGG practices, applications, and policies. Five major topics were explored in each focus group: when IGG should be used; who should perform IGG; how to approach consent for genetic database users; what systems of oversight should govern IGG practitioners; and whether to notify database users if their data are involved in law enforcement (LE) matching. Results: Participants were supportive of IGG in most scenarios, especially for cold and violent cases. The favorable attitudes toward IGG were, however, tempered by distrust of law enforcement among some participants. All participants agreed that databases must inform users if IGG is allowed, but they did not agree on how individual database users should be allowed to opt out or whether to notify them if their data are involved in specific investigations. All participants agreed that IGG should be subject to some prescriptive guidelines, regulations, or accountability mechanisms. Conclusions: These findings suggest broad public support for IGG, and interest in developing systems of accountability for its practice. Our study provides useful insight for policy makers, genomic database stewards, law enforcement, and other stakeholders in IGG's practice, and suggests multiple directions for future research. [ABSTRACT FROM AUTHOR]

Sub-Antarctic islands are expected to show a high degree of endemicity due to their remoteness. However, biogeographic affinities in the sub-Antarctic remain poorly understood, especially in the marine realm. Sub-Antarctic islands being at the crossroads between Antarctic and cold temperate regions, biodiversity characterization and biogeographic analyses are a priority for monitoring and rapidly assessing variations associated with environmental changes. One underexplored sub-Antarctic area is Crozet, a protected archipelago located halfway between Antarctica and South Africa. In this study, we investigated the shallow-water Crozet macrofaunal diversity, distribution patterns and biogeographic affinities based on the examination of fieldwork specimens via a thorough morphological identification and a genetic characterisation. The resulting dataset provides an important baseline for further studies and conservation strategies, compiling the first genetic and taxonomic database for the Crozet archipelago. In total, 100 morphotypes were found, belonging to nine different phyla, among which arthropods (32), molluscs (18) and echinoderms (17) were the richest. Forty-seven morphotypes were identified to the species level, among which 20 were reported in Crozet for the first time. This confirms that Crozet is a poorly known region, even compared to other sub-Antarctic areas. A large proportion of species (62%) had circum Southern Ocean or circum subAntarctic distributions. These species were mostly shared with Kerguelen (72%), the Magellan Province (64%), and Prince Edward Islands (64%), confirming the patterns found in macroalgae and specific macrofaunal groups. However, this large-distribution statement needs to be counterbalanced by the detection (genetic data) of more restricted distributions than expected in four study cases (the tanaid Apseudes spectabilis, the nudibranch Doris kerguelenensis, the polychaete Neanthes kerguelensis and the chiton Hemiarthrum setulosum). Considering that most morphotypes had no genetic data available from other regions, the proportion of morphotypes with restricted distribution is likely to increase alongside future investigations. In addition, we also found a few cases of unrecognized diversity that might lead to the descriptions of new species, some likely to be endemic to Crozet (e.g., within the polychaete genus Harmothoe and the bryozoan genus Antarctothoa). Altogether, this stresses the need to maintain conservation efforts in Crozet and pursue integrative investigations in order to highlight and protect its unusual diversity. [ABSTRACT FROM AUTHOR]

Periodontal disease, a multifactorial inflammatory condition affecting the supporting structures of the teeth, has been increasingly recognized for its association with various systemic diseases. Understanding the molecular comorbidities of periodontal disease is crucial for elucidating shared pathogenic mechanisms and potential therapeutic targets. In this study, we conducted comprehensive literature and biological database mining by utilizing DisGeNET2R for extracting gene–disease associations, Romin for integrating and modeling molecular interaction networks, and Rentrez R libraries for accessing and retrieving relevant information from NCBI databases. This integrative bioinformatics approach enabled us to systematically identify diseases sharing associated genes, proteins, or molecular pathways with periodontitis. Our analysis revealed significant molecular overlaps between periodontal disease and several systemic conditions, including cardiovascular diseases, diabetes mellitus, rheumatoid arthritis, and inflammatory bowel diseases. Shared molecular mechanisms implicated in the pathogenesis of these diseases and periodontitis encompassed dysregulation of inflammatory mediators, immune response pathways, oxidative stress pathways, and alterations in the extracellular matrix. Furthermore, network analysis unveiled the key hub genes and proteins (such as TNF, IL6, PTGS2, IL10, NOS3, IL1B, VEGFA, BCL2, STAT3, LEP and TP53) that play pivotal roles in the crosstalk between periodontal disease and its comorbidities, offering potential targets for therapeutic intervention. Insights gained from this integrative approach shed light on the intricate interplay between periodontal health and systemic well-being, emphasizing the importance of interdisciplinary collaboration in developing personalized treatment strategies for patients with periodontal disease and associated comorbidities. [ABSTRACT FROM AUTHOR]

Porphyria is a group of rare metabolic disorders caused by mutations in the genes encoding crucial enzymes in the heme biosynthetic pathway. However, the lack of comprehensive genetic analysis of porphyria patients in the Chinese population makes identifying and diagnosing carriers of the condition challenging. Using the ChinaMAP database, we determined the frequencies of P/LP porphyria-associated gene variants according to the ACMG guidelines. We also calculated the carrier rates and prevalence of each type of porphyria in the Chinese population under Hardy–Weinberg equilibrium. Compared with the variants in the gnomAD database, the genetic spectrum of porphyria-related P/LP variants in the Chinese population is distinct. In the ChinaMAP database, we identified 23 variants. We estimated the carrier rates for autosomal dominant porphyrias (AIP, HCP, VP, PCT) in the Chinese population to be 1/1059, 1/1513, 1/10588, and 1/1765, respectively. For autosomal recessive porphyrias (ADP, EPP, HEP, CEP), the estimated carrier rates were 1/5294, 1/2117, 1/1765, and 1/2647, respectively, with predicted prevalence rates of 8.92 × 10−9, 7.51 × 10−5, 8.02 × 10−8, and 3.57 × 10−8, respectively. Notably, 12 of the variants we identified were unique to the Chinese population. The predicted prevalence rate of EPP was the highest among the various types of porphyria in the Chinese population, while the others were moderate to low. This is the first comprehensive genetic study on porphyria in the Chinese population. Clarifying the genetic characteristics of various porphyria types among the Chinese population provides scientifically sound reference data for both research and genetic screening to identify porphyria carriers. [ABSTRACT FROM AUTHOR]

Objective: This study examines the causal effects of varying exercise intensities on type 2 diabetes mellitus (T2D) through Mendelian randomization (MR) analysis, using genetic variants as instrumental variables. Methods: A two-sample MR analysis was performed, employing Inverse Variance Weighted (IVW) as the primary method, supported by weighted median, MREgger regression, MR-PRESSO, and MR robustness-adjusted contour scores. Data were obtained from the International Exercise Genetics Database (IEGD) and the Global Diabetes Research Consortium (GRC), encompassing over 150,000 individuals for exercise intensity and around 200,000 T2D patients and controls. SNPs linked to exercise intensity were selected based on genome-wide significance (P < 5 × 10^-8) and linkage disequilibrium criteria (distance >10,000 kb, r^2 < 0.001). Results: The IVW analysis suggested that high-intensity exercise might reduce T2D risk, but the association was not statistically significant (OR = 0.667, 95% CI = 0.104-4.255, P = 0.667). The wide confidence interval indicates uncertainty in the effect estimate. Low-intensity exercise showed no significant effect on T2D risk (OR ~ 1.0). Sensitivity analyses, including weighted median and MR-Egger regression, confirmed no significant association between high-intensity exercise and T2D risk. The MR-PRESSO analysis found no significant outliers, and the global test for pleiotropy was non-significant (P = 0.455). Cochran's Q test for heterogeneity in the IVW analysis was non-significant (Q = 12.45, P = 0.234), indicating consistency among SNP-derived estimates. Conclusion: High-intensity exercise potentially reduces T2D risk, but the association is not statistically significant. Further research is needed to understand the complex relationship between exercise intensity and T2D. [ABSTRACT FROM AUTHOR]

Summary Obesity is a major public health concern associated with a higher risk of various comorbidities. Some studies have explored the impact of obesity on cognitive function and, conversely, how lower intelligence might increase the risk of later obesity. The aim of this study is to analyze a complex relationship between body mass index (BMI) and intelligence quotient (IQ), employing a comprehensive approach, including a systematic review, meta‐analysis, and Mendelian randomization (MR). We extracted the data from Medline and Embase to identify relevant studies published since June 22, 2009. MR analysis relied on genetic databases such as the Genome‐Wide Association Study (GWAS) and the Genetic Investigation of Anthropometric Traits (GIANT) to explore potential causal relationships. The systematic review and meta‐analysis encompassed 34 and 17 studies, respectively. They revealed a substantial correlation between obesity and reduced IQ, particularly notable among school‐age children (mean difference −5.26; 95% CI: −7.44 to −3.09). Notably, within the IQ subgroup, verbal IQ also exhibited a significant association with a mean difference of −7.73 (95% CI: −14.70 to −0.77) in school‐age children. In contrast, the MR did not unveil a significant causal relationship between BMI and IQ, both in childhood and adulthood. This comprehensive analysis underscores a significant correlation between BMI and IQ, particularly in school‐age children. However, the MR analysis implies a potentially weaker causal relationship. Future large‐scale cohort studies should address potential confounding factors to provide further insights into the BMI‐IQ relationship. [ABSTRACT FROM AUTHOR]

This article explores various methods for tracing the geographic origin of illegally traded wildlife. It discusses the use of trade records, elemental signatures, and molecular genetics analysis as means to determine the source of confiscated animals and their products. The article emphasizes the importance of combining these approaches and establishing comprehensive databases to improve traceability and combat illegal trade. It also suggests the need for global action programs to reduce consumer demand, strengthen law enforcement measures, and promote sustainable alternatives to wildlife products in order to prevent the illegal wildlife trade and conserve biodiversity. [Extracted from the article]

Canines are an important model system for genetics and evolution. Recent advances in sequencing technologies have enabled the creation of large databases of genetic variation in canines, but analyses of allele sharing among canine groups have been limited. We applied GeoVar, an approach originally developed to study the sharing of single nucleotide polymorphisms across human populations, to assess the sharing of genetic variation among groups of wolves, village dogs, and breed dogs. Our analysis shows that wolves differ from each other at an average of approximately 2.3 million sites while dogs from the same breed differ at nearly 1 million sites. We found that 22% of the variants are common across wolves, village dogs, and breed dogs, that ~16% of variable sites are common across breed dogs, and that nearly half of the differences between two dogs of different breeds are due to sites that are common in all clades. These analyses represent a succinct summary of allele sharing across canines and illustrate the effects of canine history on the apportionment of genetic variation. [ABSTRACT FROM AUTHOR]

The SETD1B gene, located on chromosome 12q24, is one of the chromatin‐modifying genes involved in epigenetic regulation of gene transcription. The phenotype of pathogenic variants in the SETD1B gene includes intellectual disability, seizures, and language delay (IDDSELD, OMIM 619000). In this study, we present a family consisting of consanguineous parents who died of cancer and their offspring. This family includes two cases diagnosed with autism spectrum disorder (ASD); six cases diagnosed with schizophrenia, bipolar disorder, or schizoaffective disorder; there cases diagnosed with cancer; and five cases who died of unknown causes in early childhood. Three affected members of this family agreed to genetic testing. We used whole exome sequencing. We report a novel in‐frame deletion variant of the SETD1B gene in a family with cases diagnosed with schizoaffective disorder and ASD without seizures and intellectual disability. It was found that the phenotypic features were inherited for at least three generations in the family we presented, and it was shown that the pathogenic variant of the SETD1B gene was transmitted from the affected parent to his affected children. In addition, the father was diagnosed with both schizoaffective disorder and leukemia. We proposed an association between rare variants of SETD1B and phenotypes of ASD and schizoaffective disorder without seizures and intellectual disability. The SETD1B gene is included in both the ASD genetic database of SFARI (https://gene.sfari.org/) and the cancer database of COSMIC (https://cancer.sanger.ac.uk/cosmic). However, there are very few reports of SETD1B gene variants as clinical entities. To our knowledge, the SETD1B gene variant has not been previously reported in an individual diagnosed with both a neuropsychiatric disorder and cancer. [ABSTRACT FROM AUTHOR]

Background: Despite being a major global cause of mortality, the exact underlying mechanisms of cardiovascular diseases (CVDs) remain uncertain. This study aimed to elucidate the possible pathological connection between circulating activated immune cell types and the advancement of CVD. Methods: A two-sample Mendelian randomization analysis was performed on publicly available genetic databases to examine the potential causal relationships among 731 immune phenotypes and CVD risks. The study focused on four distinct immune signatures: relative cell counts (RC), absolute cell counts (AC), morphological parameters (MP), and median fluorescence intensities (MFI). A sensitivity analysis was performed to assess the findings' consistency, robustness, and potential pleiotropic effects. Results: Significant associations between CVD and various immunophenotypes were observed in this study. Specifically, two phenotypes exhibited protective effects against CVD. The odds ratio (OR) for activated and secretory CD4+ regulatory T-cells (Tregs) was 0.757 [95% confidence interval (CI): 0.628–0.913; p = 0.004], whereas that for B-cell activating factor receptor on IgD−CD38+ memory B-cells was 0.654 (95% CI: 0.468–0.915; p = 0.013). Conversely, three major immunophenotypes were linked to heightened risks of CVD: CD80 on myeloid dendritic cells (OR: 1.181; 95% CI: 1.015–1.376; p = 0.032), the proportion of CD28+ CD45RA+ CD8+ T-cells in total T-cell population (OR: 1.064; 95% CI: 1.002–1.128; p = 0.041), and the proportion of CD28−CD45RA+ CD8+ T-cells in total T-cell population (OR: 1.005; 95% CI: 1.000–1.011; p = 0.045). Conclusion: This study underscores significant correlations between specific immune phenotypes and the risks associated with CVD onset, thus providing valuable perspectives for forthcoming clinical inquiries. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social and communication difficulties, along with repetitive behaviors. While genetic factors play a significant role in ASD, the precise genetic landscape remains complex and not fully understood, particularly in non-syndromic cases. The study performed an in silico comparison of three genetic databases. ClinVar, SFARI Gene, and AutDB were utilized to identify relevant gene subset and genetic variations associated with non-syndromic ASD. Gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) network analysis were conducted to elucidate the biological significance of the identified genes. The integrity of ASD-related gene subset and the distribution of their variations were statistically assessed. A subset of twenty overlapping genes potentially specific for non-syndromic ASD was identified. GSEA revealed enrichment of biological processes related to neuronal development and differentiation, synaptic function, and social skills, highlighting their importance in ASD pathogenesis. PPI network analysis demonstrated functional relationships among the identified genes. Analysis of genetic variations showed predominance of rare variants and database-specific distribution patterns. The results provide valuable insights into the genetic landscape of ASD and outline the genes and biological processes involved in the condition, while taking into account that the study relied exclusively on in silico analyses, which may be subject to biases inherent to database methodologies. Further research incorporating multi-omics data and experimental validation is warranted to enhance our understanding of non-syndromic ASD genetics and facilitate the development of targeted research, interventions and therapies. [ABSTRACT FROM AUTHOR]

The therapeutic response to lithium in patients with bipolar disorder is highly variable and has a polygenic basis. Genome-wide association studies investigating lithium response have identified several relevant loci, though the precise mechanisms driving these associations are poorly understood. We aimed to prioritise the most likely effector gene and determine the mechanisms underlying an intergenic lithium response locus on chromosome 21 identified by the International Consortium on Lithium Genetics (ConLi+Gen). We conducted in-silico functional analyses by integrating and synthesising information from several publicly available functional genetic datasets and databases including the Genotype-Tissue Expression (GTEx) project and HaploReg. The findings from this study highlighted TMPRSS15 as the most likely effector gene at the ConLi+Gen lithium response locus. TMPRSS15 encodes enterokinase, a gastrointestinal enzyme responsible for converting trypsinogen into trypsin and thus aiding digestion. Convergent findings from gene-based lookups in human and mouse databases as well as co-expression network analyses of small intestinal RNA-seq data (GTEx) implicated TMPRSS15 in the regulation of intestinal nutrient absorption, including ions like sodium and potassium, which may extend to lithium. Although the findings from this study indicated that TMPRSS15 was the most likely effector gene at the ConLi+Gen lithium response locus, the evidence was circumstantial. Thus, the conclusions from this study need to be validated in appropriately designed wet-lab studies. The findings from this study are consistent with a model whereby TMPRSS15 impacts the efficacy of lithium treatment in patients with bipolar disorder by modulating intestinal lithium absorption. • TMPRSS15 is a novel regulator of lithium response in patients with bipolar disorder. • It is the most likely effector gene at a known lithium response locus. • The gene encodes enterokinase (ENTK), a key modulator of intestinal absorption. • ENTK likely impacts lithium response through the modulation of lithium absorption. [ABSTRACT FROM AUTHOR]

Simple Summary: In forensic entomology, insects are used to estimate the time since death and to answer other investigative questions, such as determining if the body was moved postmortem or identifying the season of death. In funerary archeoentomology, insects provide information related to the season of death, body transfer, and funerary practices. To obtain this information, the correct identification of specimens collected from the scene is fundamental. In old cases and archeological contexts, the majority of entomological evidence samples found are fly puparia, barrel-like structures formed from the third-instar larval cuticle where metamorphosis takes place. Despite recent publications of identification keys for certain fly larvae and adults, there is still a lack of tools for puparium identification. This problem is exacerbated by the scarcity of diagnostic features present on the puparia. This paper critically reviews the techniques available for puparium identification in addition to traditional morphological analysis. It describes DNA-based approaches and chemical analyses of cuticular lipids and hydrocarbons, highlighting the importance of using non-invasive methods to guarantee the repeatability of the analysis—a key element in forensic science—or to preserve precious and unique specimens from museum collections. Diptera identification is fundamental in forensic entomology as well as in funerary archeoentomology, where the challenge is exacerbated by the presence of immature stages such as larvae and puparia. In these two developmental stages, specimens possess a very limited number of diagnostic features, and for puparia, there is also a lack of identification tools such as descriptions and identification keys. Morphological analysis, DNA-based techniques, and cuticular chemical analyses all show good potential for species identification; however, they also have some limitations. DNA-based identification is primarily hindered by the incompleteness of genetic databases and the presence of PCR inhibitors often co-extracted from the puparial cuticle. Chemical analysis of the cuticle is showing promising results, but this approach is also limited by the insufficient profile database and requires specific, expensive equipment, as well as trained personnel. Additionally, to ensure the repeatability of the analysis—a critical aspect in forensic investigations—and to preserve precious and unique specimens from museum collections, non-invasive protocols and techniques must be prioritized for species identification. [ABSTRACT FROM AUTHOR]

The supervised machine learning method is often used for biomedical relationship extraction. The disadvantage is that it requires much time and money to manually establish an annotated dataset. Based on distant supervision, the knowledge base is combined with the corpus, thus, the training corpus can be automatically annotated. As many biomedical databases provide knowledge bases for study with a limited number of annotated corpora, this method is practical in biomedicine. The clinical significance of each patient's genetic makeup can be understood based on the healthcare provider's genetic database. Unfortunately, the lack of previous biomedical relationship extraction studies focuses on gene–gene interaction. The main purpose of this study is to develop extraction methods for gene–gene interactions that can help explain the heritability of human complex diseases. This study referred to the information on gene–gene interactions in the KEGG PATHWAY database, the abstracts in PubMed were adopted to generate the training sample set, and the graph kernel method was adopted to extract gene–gene interactions. The best assessment result was an F1-score of 0.79. Our developed distant supervision method automatically finds sentences through the corpus without manual labeling for extracting gene–gene interactions, which can effectively reduce the time cost for manual annotation data; moreover, the relationship extraction method based on a graph kernel can be successfully applied to extract gene–gene interactions. In this way, the results of this study are expected to help achieve precision medicine. [ABSTRACT FROM AUTHOR]

Rhododendron williamsianum Rehder & E. H. Wilson 1913, is a plant with important horticultural value. Here we report its chloroplast genome. The total length of the chloroplast genome was 205,424 bp, with a GC content of 35.8%. It consisted of a 107,968 bp large single copy, a 2606 bp small single copy, and a pair of 47,425 bp inverted repeats separating them. Within the chloroplast genome, there were a total of 110 unique genes, which included 76 protein-coding genes, 4 rRNA genes, and 30 tRNA genes. Our phylogenetic analyses indicated that R. williamsianum was closely genetically related to R. sutchuenense and R. jingangshanicum. The findings from this study not only contribute to the genetic database of Rhododendron plants but also have implications for evolutionary research within the family Ericaceae. [ABSTRACT FROM AUTHOR]

Background: Observational studies have indicated that immune dysregulation in primary sclerosing cholangitis (PSC) primarily involves intestinal-derived immune cells. However, the causal relationship between peripheral blood immune cells and PSC remains insufficiently understood. Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was implemented to determine the causal effect between PBC and 731 immune cells. All datasets were extracted from a publicly available genetic database. The standard inverse variance weighted (IVW) method was selected as the main method for the causality analysis. Cochran's Q statistics and MR-Egger intercept were performed to evaluate heterogeneity and pleiotropy. Results: In forward MR analysis, the expression ratios of CD11c on CD62L+ myeloid DC (OR = 1.136, 95% CI = 1.032-1.250, p = 0.009) and CD62L-myeloid DC AC (OR = 1.267, 95% CI = 1.086-1.477, p = 0.003) were correlated with a higher risk of PSC. Each one standard deviation increase of CD28 on resting regulatory T cells (Treg) (OR = 0.724, 95% CI = 0.630-0.833, p < 0.001) and CD3 on secreting Treg (OR = 0.893, 95% CI = 0.823-0.969, p = 0.007) negatively associated with the risk of PSC. In reverse MR analysis, PSC was identified with a genetic causal effect on EM CD8+ T cell AC, CD8+ T cell AC, CD28-CD127- CD25++ CD8+ T cell AC, CD28- CD25++ CD8+ T cell AC, CD28- CD8+ T cell/CD8+ T cell, CD28- CD8+ T cell AC, and CD45 RA- CD28- CD8+ T cell AC. Conclusion: Our study indicated the evidence of causal effects between PSC and immune cells, which may provide a potential foundation for future diagnosis and treatment of PSC. [ABSTRACT FROM AUTHOR]

Motivation: Alignment of reads to a reference genome sequence is one of the key steps in the analysis of human whole-genome sequencing data obtained through Next-generation sequencing (NGS) technologies. The quality of the subsequent steps of the analysis, such as the results of clinical interpretation of genetic variants or the results of a genome-wide association study, depends on the correct identification of the position of the read as a result of its alignment. The amount of human NGS whole-genome sequencing data is constantly growing. There are a number of human genome sequencing projects worldwide that have resulted in the creation of large-scale databases of genetic variants of sequenced human genomes. Such information about known genetic variants can be used to improve the quality of alignment at the read alignment stage when analysing sequencing data obtained for a new individual, for example, by creating a genomic graph. While existing methods for aligning reads to a linear reference genome have high alignment speed, methods for aligning reads to a genomic graph have greater accuracy in variable regions of the genome. The development of a read alignment method that takes into account known genetic variants in the linear reference sequence index allows combining the advantages of both sets of methods. Results: In this paper, we present the minimap2_index_modifier tool, which enables the construction of a modified index of a reference genome using known single nucleotide variants and insertions/deletions (indels) specific to a given human population. The use of the modified minimap2 index improves variant calling quality without modifying the bioinformatics pipeline and without significant additional computational overhead. Using the PrecisionFDA Truth Challenge V2 benchmark data (for HG002 short-read data aligned to the GRCh38 linear reference (GCA_000001405.15) with parameters k = 27 and w = 14) it was demonstrated that the number of false negative genetic variants decreased by more than 9500, and the number of false positives decreased by more than 7000 when modifying the index with genetic variants from the Human Pangenome Reference Consortium. [ABSTRACT FROM AUTHOR]

Introduction: Immune cells are dynamic in the inflammatory environment and play a key role in eradicating periodontal pathogens, modulating immune responses, and instigating tissue destruction. Identifying specific immune cell phenotypes associated with periodontitis risk is essential for targeted immunotherapeutic interventions. However, the role of certain specific immune cell phenotypes in the development of periodontitis is unknown. Mendelian randomization offers a novel approach to reveal causality and address potential confounding factors through genetic instruments. Methods: This two-sample Mendelian randomization study assessed the causal relationship between 731 immune cell phenotypes and periodontitis using the inverse variance weighting method with the GWAS catalog genetic database. Methodological robustness was ensured through Cochran's Q test, MR-Egger regression, MR-PRESSO, and Leave-One-Out analysis. Results: 14 immune cell phenotypes showed potential positive causal associations with periodontitis risk (p < 0.05), suggesting an increased risk, while 11 immune cell phenotypes exhibited potential negative causal associations (p < 0.05), indicating a reduced risk. No significant heterogeneity or pleiotropy was observed. Conclusion: This study underscores certain immune cell types as potential periodontitis risk biomarkers, laying a theoretical foundation for future individualized treatment and precision medicine development. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify the disease-causing allele of retinitis pigmentosa, a heterogeneous genetic disorder in a single affected family. METHODOLOGY: A cross-sectional descriptive study was conducted at the Sindh Institute of Ophthalmology & Visual Sciences Hyderabad from December 2022 to December 2023, with approval from the SIOVS ethical committee. A consanguineous pedigree with multiple affected members was included, while pedigrees with only one affected member or secondary causes of vision loss were excluded. After getting informed consent, each enrolled participant's blood samples (10 cc) were collected, and DNA was extracted. The family was subjected to Sanger sequencing for the CLCC1 gene. RESULTS: In this study, one reported c.C75A, p.Asp25Glu allele in the CLCC1 gene was identified from an endogamous pedigree in Sindh, Pakistan. The identified c.C75A, p.Asp25Glu allele is a common cause of autosomal recessive retinitis pigmentosa (arRP) in Pakistani-affected individuals. This allele is estimated to have occurred 2000-5000 years ago and has been transmitted to affected individuals of Pakistani origin and global descent across various geographical regions. All the affected patients underwent detailed clinical investigations, including fundus photography and optical coherence tomography, to confirm the retinitis pigmentosa symptoms. The Sanger sequencing method was used to detect pathogenic variants, and bioinformatics tools were utilized to investigate the pathogenesis of identified alleles and compare phenotype-genotype correlations. CONCLUSION: The finding of frequent disease-causing alleles from Pakistani-affected patients will significantly improve existing genetic databases and facilitate more accurately the affected diagnosis of gene testing. [ABSTRACT FROM AUTHOR]

Introduction: Conclusive molecular genetic diagnoses in inherited retinal diseases remains a major challenge due to the large number of variants of uncertain significance (VUS) identified in genetic testing. Here, we determined the genotypic and phenotypic spectrum of ABCA4 gene variants in a cohort of Canadian inherited retinal dystrophy subjects. Methods: This retrospective study evaluated 64 subjects with an inherited retinal dystrophy diagnosis with variants in the ABCA4 gene. Pathogenicity of variants was assessed by comparison to genetic databases and in silico modelling. ABCA4 variants classified as VUS were further evaluated using a cryo-electron structural model of the ABCA4 protein to predict impact on protein function and were also assessed for evolutionary conservation. Results: Conclusive disease-causing biallelic ABCA4 variants were detected in 52 subjects with either Stargardt's disease, cone-rod dystrophy, macular dystrophy, or pattern dystrophy. A further 14 variants were novel comprising 1 nonsense, 1 frameshift, 3 splicing, and 9 missense variants. Based on in silico modelling, protein modelling and evolutionary conservation from human to zebrafish, we re-classified 5 of these as pathogenic and a further 3 as likely pathogenic. We also added to the ABCA4 phenotypic spectrum seen with four known pathogenic variants (c.2161-2A>G; Leu296Cysfs*4; Arg1640Gln; and Pro1380Leu). Conclusions: This study expands the genotypic and phenotypic spectrum of ABCA4 disease-associated variants. By panel-based genetic testing, we identified 14 novel ABCA4 variants of which 8 were determined to be disease-causing or likely disease-causing. These methodologies could circumvent somewhat the need for labour intensive in vitro and in vivo assessments of novel ABCA4 variants. [ABSTRACT FROM AUTHOR]

This study was aimed at developing a molecular genetic database that allows the certification of the pecan cultivars planted in Brazil, based on reference cultivars from the USA. We used a set of 10 nSSR and 10 cpSSR markers for cultivar identification and characterization. The database developed is an instrument for certification of cultivars, characterization of potential new cultivars, and selection of material for pecan breeding. The CertiBase database is composed of genotypes and haplotypes characterized for 40 reference pecan cultivars, while the CertiBase algorithm for plant identification is implemented in a user-friendly free software. Varietal certification of cultivars will bring more security to the entire production chain, in addition to enabling the characterization of the ancestry of potential new cultivars and establishment of breeding programs of pecan in Brazil. [ABSTRACT FROM AUTHOR]

The article discusses the prevalence of lipodystrophy and lipodystrophy-like phenotypes, which are conditions characterized by altered adipose tissue distribution. The study found that lipodystrophy-like phenotypes are more common than the clinical or genetic prevalence of familial partial lipodystrophy (FPLD), a rare disease. The authors propose using a fat mass ratio (FMR) derived from DEXA scans to identify individuals with lipodystrophy-like phenotypes and potentially develop targeted therapies. However, they emphasize that a comprehensive clinical assessment is necessary for a definitive diagnosis of lipodystrophy syndromes. The article also highlights the challenges in accurately estimating the prevalence of lipodystrophy due to underdiagnosis and the involvement of unidentified genes. Overall, understanding and differentiating lipodystrophy and lipodystrophy-like phenotypes can improve personalized disease management and interventions. [Extracted from the article]

Introduction: CYP2C19 plays a major role in the metabolism of various drugs. The most common genetic variants were the CYP2C19*2 and *3 alleles (rs4244285 and rs4986893, non-functional variants). In previous studies, we found that genetic polymorphisms in CYP2C19 variants influenced the active metabolites of clopidogrel and caused major adverse cardiovascular and cerebrovascular effects. However, the distribution of CYP2C19 varies among ethnic groups and according to adverse drug reactions. This study aimed to investigate the frequency of CYP2C19 genetic polymorphisms in the Thai population and analyze the differences in the frequency of CYP2C19 genetic polymorphisms between Thai and other populations. Methods: This study enrolled 211 unrelated healthy Thai individuals in total. We performed a real-time polymerase chain reaction to genotype CYP2C19*2 (681G > A) and CYP2C19*3 (636G > A). Results: In the Thai population, the CYP2C19*1 allele was the most prevalent at 70.14%, while the CYP2C19*2 and *3 alleles were found at frequencies of 25.36% and 4.50%, respectively. Conversely, the CYP2C19*3 allele was not detected in Caucasian, Hispanic, African, Italian, Macedonian, Tanzanian, or North Indian populations. The phenotypic profile of this gene revealed that the frequency of intermediate metabolizers (IMs) is nearly equal to that of extensive metabolizers (EMs), at 42.65% and 48.82% respectively, with genotypes *1/*2 (36.02%) and *1/*3 (6.63%). Likewise, poor metabolizers (PMs) with genotypes *2/*2 (6.16%), *2/*3 (2.37%), and *3/*3 (< 1%) are more prevalent in our population as well. Conclusion: The distribution of CYP2C19 genotype and phenotype influenced by non-functional alleles has potential as a pharmacogenomics biomarker for precision medicine and is dependent on an ethnic-specific genetic variation database. [ABSTRACT FROM AUTHOR]

Background: Investigating novel therapeutic strategies for colorectal cancer (CRC) is imperative. However, there is limited research on the use of drugs to target peripheral blood immune cells in this context. To address this gap, we performed a two-sample Mendelian randomization (MR) analysis to identify potential therapeutic targets for CRC. Methods: We applied two-sample MR to identify the causal relationship between peripheral blood immune cells and CRC. GWAS data were obtained from the IEU OPEN GWAS project. Based on the implications from the MR results, we conducted a comprehensive database search and genetic analysis to explore potential underlying mechanisms. We predicted miRNAs for each gene and employed extensive research for potential therapeutic applications. Results: We have identified causal associations between two peripheral immune cells and colorectal cancer. Activated & resting Treg %CD4 + cell was positively associated with the risks of CRC, while DN (CD4-CD8-) %leukocyte cell exhibited a protective role in tumor progression. NEK7 (NIMA related kinase 7) and LHX9 (LIM homeobox 9) expressed in Treg cells were positively associated with CRC risks and may play a vital role in carcinogenesis. Conclusions: This study identified causal relationship between peripheral immune cell and CRC. Treg and DN T cells were implicated to own promoting and inhibiting effects on CRC progression respectively. NEK7 and LHX9 in Treg cells were identified as potential biotarget for antitumor therapies. [ABSTRACT FROM AUTHOR]

Background: The onset and progression of chronic kidney disease (CKD) has been linked to metabolic syndrome (MetS), with the results of recent observational studies supporting a potential link between renal failure and MetS. The causal nature of this relationship, however, remains uncertain. This study thus leveraged a Mendelian Randomization (MR) approach to probe the causal link of MetS with renal failure. Methods: A genetic database was initially used to identify SNPs associated with MetS and components thereof, after which causality was evaluated through the inverse variance weighted (IVW), MR-Egger regression, and weighted media techniques. Results were subsequently validated through sensitivity analyses. Results: IVW (OR = 1.48, 95% CI = 1.21–1.82, P =1.60E−04) and weighted median (OR = 1.58, 95% CI =1.15–2.17, P = 4.64E-03) analyses revealed that MetS was linked to an elevated risk of renal failure. When evaluating the specific components of MetS, waist circumference was found to be causally related to renal failure using the IVW (OR= 1.58, 95% CI = 1.39–1.81, P = 1.74e-11), MR-Egger (OR= 1.54, 95% CI = 1.03–2.29, P = 0.036), and weighted median (OR= 1.82, 95% CI = 1.48–2.24, P = 1.17e-8). The IVW method also revealed a causal association of hypertension with renal failure (OR= 1.95, 95% CI = 1.34–2.86, P = 5.42e-04), while renal failure was not causally related to fasting blood glucose, triglyceride levels, or HDL-C levels. Conclusion: These data offer further support for the existence of a causal association of MetS with kidney failure. It is thus vital that MetS be effectively managed in patients with CKD in clinical settings, particularly for patients with hypertension or a high waist circumference who are obese. Adequate interventions in these patient populations have the potential to prevent or delay the development of renal failure. [ABSTRACT FROM AUTHOR]

Rock abrasivity is one of the main factors affecting the wear of rock-cutting tools, which is usually quantified by the CERCHAR Abrasivity Index (CAI). Researchers and engineers study tool wear and predict tool life based on the CAI of rocks. However, there is still a lack of a dataset on rock properties, especially the abrasivity of various rocks. This paper reports the abrasive dataset of 10 kinds of rocks, including sedimentary rocks, metamorphic rocks, and igneous rocks, with the aid of the CERCHAR Abrasivity Test and digital measurement techniques. The dataset comprises rock abrasivity data, point cloud data for visualization, scratch photos, CERCHAR Abrasivity Test force data, and mechanical properties (uniaxial compressive strength) of rock samples. This dataset facilitates future research on rock abrasivity and rock-cutting tool wear. [ABSTRACT FROM AUTHOR]

Genes strictly regulate the development of teeth and their surrounding oral structures. Alteration of gene regulation leads to tooth disorders and developmental anomalies in tooth, oral, and facial regions. With the advancement of gene sequencing technology, genomic data is rapidly increasing. However, the large sets of genomic and proteomic data related to tooth development and dental disorders are currently dispersed in many primary databases and literature, making it difficult for users to navigate, extract, study, or analyze. We have curated the scattered genetic data on tooth development and created a knowledgebase called 'Bioinformatics for Dentistry' (https://dentalbioinformatics.com/). This database compiles genomic and proteomic data on human tooth development and developmental anomalies and organizes them according to their roles in different stages of tooth development. The database is built by systemically curating relevant data from the National Library of Medicine (NCBI) GenBank, OMIM: Online Mendelian Inheritance in Man, AlphaFold Protein Structure Database, Reactome pathway knowledgebase, Wiki Pathways, and PubMed. The accuracy of the included data was verified from supporting primary literature. Upon data curation and validation, a simple, easy-to-navigate browser interface was created on WordPress version 6.3.2, with PHP version 8.0. The website is hosted in a cloud hosting service to provide fast and reliable data transfer rate. Plugins are used to ensure the browser's compatibility across different devices. Bioinformatics for Dentistry contains four embedded filters for complex and specific searches and free-text search options for quick and simple searching through the datasets. Bioinformatics for Dentistry is made freely available worldwide, with the hope that this knowledgebase will improve our understanding of the complex genetic regulation of tooth development and will open doors to research initiatives and discoveries. This database will be expanded in the future by incorporating resources and built-in sequence analysis tools, and it will be maintained and updated annually. [ABSTRACT FROM AUTHOR]

Objectives: The Bengal tiger Panthera tigris tigris, is an emblematic animal for Bangladesh. Despite being the apex predator in the wild, their number is decreasing due to anthropogenic activities such as hunting, urbanization, expansion of agriculture and deforestation. By contrast, captive tigers are flourishing due to practical conservation efforts. Breeding within the small captive population can produce inbreeding depression and genetic bottlenecks, which may limit the success of conservation efforts. Despite past decades of research, a comprehensive database on genetic variation in the captive and wild Bengal tigers in Bangladesh still needs to be included. Therefore, this research aimed to investigate the White Bengal tiger genome to create a resource for future studies to understand variation underlying important functional traits. Data description: Blood samples from Chattogram Zoo were collected for three white Bengal tigers. Genomic DNA for all collected samples were extracted using a commercial DNA extraction kit. Whole genome sequencing was performed using a DNBseq platform. We generated 77 Gb of whole-genome sequencing (WGS) data for three white Bengal tigers (Average 11X coverage/sample). The data we generated will establish a paradigm for tiger research in Bangladesh by providing a genomic resource for future functional studies on the Bengal white tiger. [ABSTRACT FROM AUTHOR]

Objective: Few studies have been conducted on the association between gut microbes and gastric ulcers. This paper aims to investigate the causal relationship between gut flora and gastric ulcer development using a two-sample Mendelian randomization method. Methods: Relevant single nucleotide polymorphisms were screened as instrumental genetic variables (SNPs) from the genetic variation database of the gut microbiota (MiBioGen), and the weighted median estimator of random effects (WME), inverse variance weighting (IVW) and MR-Egger regression three Mendelian randomization methods were used to study the causal association between gut microbes and gastric ulcer development. Results and Discussion: Family Lachnospiraceae, genus Eubacterium ventriosum group, genus Olsenella were risk factors for gastric ulcer, while genus Butyrivibrio, genus Odoribacter, genus Sutterella had a suggestive protective effect on gastric ulcer, but the mechanism of intestinal flora and gastric ulcer needs to be further verified, but this study still provides some theoretical basis for future studies between gastric ulcer and intestinal flora. Conclusions: In this study, a potentially positive and negative causal relationship between intestinal flora and the gastric ulcer was derived by a two-sample Mendelian analysis, from which it was known that the family Lachnospiraceae, genus Eubacterium ventricose group, genus Olsenella are risk factors for gastric ulcer. In contrast, the genus Butyrivibrio, genus Odoribacter, and genus Sutterella had suggestive protective effects against gastric ulcers. [ABSTRACT FROM AUTHOR]

Taohong Siwu Decoction (THSWD), a traditional Chinese prescription renowned for its efficacy in promoting blood circulation and alleviating blood stasis, was investigated in this study to delineate its potential active components and discern the core targets (CTs) and signaling pathways implicated in the treatment of Alzheimer's disease (AD). Initially, 25 active compounds (ACs) and 478 corresponding active ingredient targets (AITs) of THSWD were meticulously identified by scrutinizing the active ingredients and their targets through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Similarity Ensemble Approach (SEA) databases. Subsequently, a comprehensive compilation of 724 AD-related targets was assembled from the Therapeutic Target Database (TTD), DisGeNET, DrugBank, Genetic Association Database (GAD), and GeneCards databases. Through a meticulous alignment of AITs with disease-related targets, 64 overlapping targets (OTs) emerged as critical intersections. To distill the key compounds, an intricate analysis of the interrelationships among the 25 ACs and 64 OTs resulted in the identification of 21 first-level key compounds (FKCs). Further scrutiny through protein-protein interaction (PPI) analysis of the 64 OTs revealed 33 CTs. KEGG cluster analysis of these CTs yielded the top 73 pathways, forming the basis for constructing a network diagram encompassing "21 FKCs-33 CTs-73 pathways" using Cytoscape 3.7.2 software. Refining the network through the selection of topological parameters led to the identification of 19 second key components (SKCs). This information was then employed to construct a refined network, "19 SKCs-33 CTs-73 pathways", providing deeper insights into the intricate connections within the system. Further analyses culminated in the creation of a comprehensive network map, encapsulating "6 single drugs-8 potential active ingredients-13 core targets-54 signaling pathways", elucidating the multifaceted intervention of THSWD in AD. These results offered a novel perspective for understanding the pharmacodynamic material basis of THSWD and paved the way for in-depth investigations into its mechanisms of action and clinical applications in the context of AD. [ABSTRACT FROM AUTHOR]

Elasmobranchs (sharks and rays) are the most threatened marine vertebrates, particularly in tropical and subtropical areas. Their population status is often poorly understood due to insufficient information. Despite reportedly harbouring critical elasmobranch habitats, the Banc d'Arguin National Park (PNBA) in Mauritania lacks comprehensive and updated information on the diversity of elasmobranch species in the area. We developed a baseline inventory based on morphological and molecular identification and metabarcoding. DNA barcoding of tissue samples from elasmobranch processing sites and freshly sampled specimens was used to build a genetic reference database of local elasmobranch species. The richness and diversity of species in the PNBA were described via metabarcoding of seawater eDNA samples using an elasmobranch-specific assay and our reference database. We detected 27 species, including 12 new species records for the PNBA. We further uncover potentially undescribed species of Gymnura and Torpedo, while taxonomic corrections are noted for previously reported species. In particular, the reportedly abundant Mustelus mustelus was absent from tissue and eDNA samples, while M. punctulatus was detected instead. Taxa that have anecdotally become regionally extinct or rare (e.g., sawfishes, wedgefishes, lemon sharks) were not detected, highlighting local species diversity shifts within the last few decades. Results show that 67.9% of elasmobranch species in the PNBA are threatened with extinction according to the IUCN Red List of Threatened Species. This study emphasises the importance of taxonomic identification in support of species management and provides a baseline to inform future studies and conservation measures to avoid further species losses. [ABSTRACT FROM AUTHOR]

In this work is addressed the need for international judicial cooperation and especially the forensic cooperation by using forensic databases. It also describes how forensic data is exchanged within the European Union by detailing the AFIS data systems, IBIS and the National Judicial Genetic Data System. [ABSTRACT FROM AUTHOR]

Background: Environmental stress factors, such as biotic and abiotic stress, are becoming more common due to climate variability, significantly affecting global maize yield. Transcriptome profiling studies provide insights into the molecular mechanisms underlying stress response in maize, though the functions of many genes are still unknown. To enhance the functional annotation of maize-specific genes, MaizeGDB has outlined a data-driven approach with an emphasis on identifying genes and traits related to biotic and abiotic stress. Results: We mapped high-quality RNA-Seq expression reads from 24 different publicly available datasets (17 abiotic and seven biotic studies) generated from the B73 cultivar to the recent version of the reference genome B73 (B73v5) and deduced stress-related functional annotation of maize gene models. We conducted a robust meta-analysis of the transcriptome profiles from the datasets to identify maize loci responsive to stress, identifying 3,230 differentially expressed genes (DEGs): 2,555 DEGs regulated in response to abiotic stress, 408 DEGs regulated during biotic stress, and 267 common DEGs (co-DEGs) that overlap between abiotic and biotic stress. We discovered hub genes from network analyses, and among the hub genes of the co-DEGs we identified a putative NAC domain transcription factor superfamily protein (Zm00001eb369060) IDP275, which previously responded to herbivory and drought stress. IDP275 was up-regulated in our analysis in response to eight different abiotic and four different biotic stresses. A gene set enrichment and pathway analysis of hub genes of the co-DEGs revealed hormone-mediated signaling processes and phenylpropanoid biosynthesis pathways, respectively. Using phylostratigraphic analysis, we also demonstrated how abiotic and biotic stress genes differentially evolve to adapt to changing environments. Conclusions: These results will help facilitate the functional annotation of multiple stress response gene models and annotation in maize. Data can be accessed and downloaded at the Maize Genetics and Genomics Database (MaizeGDB). [ABSTRACT FROM AUTHOR]

To detect environmental factors, which may be possible risk factors in the disease course of Fuchs' endothelial corneal dystrophy (FECD). Evaluation of patients with FECD registered in the FECD genetics database of the Center for Ophthalmology, University Hospital Cologne. For the evaluation, disease onset, central corneal thickness, best spectacle corrected visual acuity (BSCVA, logMAR), and modified Krachmer grading (grades 1–6) were correlated with the presence of diabetes mellitus (DM), body mass index (BMI), and smoking behavior. To put the age-related increase in Krachmer grading into perspective, a correction of grading were formed. Depending on the variables studied, differences between groups were examined by Mann–Whitney U test and chi-square test. The significance level was 5%. 403 patients with FECD were included in the analysis. The mean age of the patients was 70.0 ± 10.32 (range 28–96) years. The mean age at diagnosis of those patients was 63.1 ± 13.2 years. The female-to-male ratio was 1.46:1. Patients with a BMI > 30.0 kg/m2 developed FECD significantly earlier than patients with a BMI < 30 kg/m2, p = 0.001. Patients with DM showed significantly more often an Krachmer grade of 5, p = 0.015. Smoking had a negative effect on Krachmer grading (p = 0.024). Using the mediation analysis, the presence of DM correlated Krachmer Grade 5 (p = 0.015), and the presence of DM correlated with BMI > 30.0 kg/m2 (p = 0.012). In addition to smoking and DM our study shows for the first time that obesity may have a negative impact on the development of FECD. Whether dietary interventions and hormones can influence the development or progression of the disease needs to be investigated in future studies. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms are most common type of genetic variation in human genome. Analyzing genetic variants can help us better understand the genetic basis of diseases and develop predictive models which are useful to identify individuals who are at increased risk for certain diseases. Several SNP analysis tools have already been developed. For running these tools, the user needs to collect data from various databases. Secondly, often researchers have to use multiple variant analysis tools for cross validating their results and increase confidence in their findings. Extracting data from multiple databases and running multiple tools at a time, increases complexity and time required for analysis. There are some web-based tools that integrate multiple genetic variant databases and provide variant annotations for a few tools. These approaches have some limitations such as retrieving annotation information, filtering common pathogenic variants. The proposed web-based tool, namely IPSNP: An Integrated Platform for Predicting Impact of SNPs is written in Django which is a python-based framework. It uses RESTful API of MyVariant.info to extract annotation information of variants associated with a given gene, rsID, HGVS format variants specified in a VCF file for 29 tools. The results are in the form of a CSV file of predictions (1) derived from the consensus decision, (2) a file having annotations for the variants associated with the given gene, (3) a file showing variants declared as pathogenic commonly by the selected tools, and (4) a CSV file containing chromosome coordinates based on GRCh37 and GRCh38 genome assemblies, rsIDs and proteomic data, so that users may use tools of their choice and avoiding manual parameter collection for each tool. IPSNP is a valuable resource for researchers and clinicians and it can help to save time and effort in discovering the novel disease-associated variants and the development of personalized treatments. [ABSTRACT FROM AUTHOR]

Currently, the genus Zenopsis, also known as silver John Dory, comprises at least five valid species with a wide range of distribution. However, recent studies have proposed the existence of a new Zenopsis species inhabiting the Indian Ocean, and a preliminary search in the Barcode of Life Database reveals the presence of different barcode index numbers (BIN) for the nominal species Zenopsis conchifer. In the Southwest Atlantic Ocean (SWA), Z. conchifer is the only species reported so far. Therefore, the aim of this work was to evaluate, at the molecular level, the potential taxonomic diversity within the genus Zenopsis and to assess if the species occurring in the SWA corresponds with Z. conchifer. Using data available in worldwide genetic databases, a maximum likelihood tree, a BIN , and an automatic barcode gap discovery analysis were carried out. Additionally, specimens sampled from the SWA were morphologically compared with specimens from different parts of its distribution using available data. The specific identity at the molecular level of specimens occurring in the SWA was confirmed as Z. conchifer. The results of the molecular analysis highlight the existence of hidden specific diversity within the genus. [ABSTRACT FROM AUTHOR]

This document discusses the challenges of diagnosing the causes of unexplained child deaths and presents a study on the use of molecular autopsy to identify genetic variations associated with these deaths. Traditional autopsies are not always acceptable to parents due to religious and cultural beliefs, so molecular autopsy, which involves DNA sequencing, offers a promising alternative. The study used stored neonatal dried blood spots to conduct clinical exome sequencing and found that 88.9% of cases had genetic variations associated with the cause of death. The study suggests that molecular autopsies using clinical exome sequencing can be a feasible and effective method for investigating unexplained child deaths. [Extracted from the article]

The popularity of digital devices seems to provide a new observational variable for early identification and prevention of suicide with the development of the information technology era. Nevertheless, whether it is the use of digital devices that alters suicide risk or suicide risk manifests itself through change digital device use needs to be further explored. Bidirectional Mendelian randomization (MR) analysis was used to explore potential causal relationships in the perspective of genetic prediction. We collected publicly available digital device use and suicide risk summary statistics genome-wide association data from UK Biobank, Neale Lab and FinnGen genetic databases. We used inverse variance weighting methods to assess MR estimates. For robustness of the results, we performed further tests of heterogeneity and pleiotropy. In the Phase 1 results, we did not observe any effect of the length of digital device use on the suicide risk, while the results of Phase 2 suggested a significant positive association between suicide risk and the length of mobile phone use (IVW OR, 1.04; 95%CI, 1.01–1.06; P = 0.002), but this significance disappeared after adjusting for confounders of mental and affective disorders. In this bidirectional MR analysis, we observed that People at high risk of suicide may be more addicted to digital device use, but more detailed GWAS data and research methods to validate this finding are required. • This study is the first to explore the bidirectional causal relationship between digital device use and suicide risk. • Our study finds that length of use of digital devices does not change suicide risk. • People at high risk of suicide may be more addicted to digital device use. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify the pathogenic alleles in primary congenital glaucoma patients for early cure of the disease METHODOLOGY: A cross-sectional descriptive study was carried out after approval from the ethical committee of SIOVS from December 2022 to November 2023 at Sindh Institute of Ophthalmology & Visual Sciences, Hyderabad. The consanguineous pedigree consisting of more than one affected was included, and the pedigree consists only one affected or secondary cause of vision loss was excluded. After getting informed consent, ten cc blood samples from all available participants in the pedigree were drawn, and DNA was extracted. The ARMS Assay and Sanger sequencing methods were adapted to analyze the CYP1B1 gen. RESULTS: In the present study, one novel c.1187C>T, p.Pro396Leu and one reported c.1169G>A, p.Arg390His allele in CYP1B1 gene were found in two isolated pedigrees enrolled from Sindh Pakistan. ARMS Assay method and the Sanger sequencing method were adopted to detect pathogenic variants. Bioinformatics tools were used to analyze the pathogenesis of identified alleles and compare phenotype -genotype correlation. CONCLUSION: The findings of novel and frequently reported mutations have a significant role in advancing genetic testing protocols, enabling more accurate targeting of diagnoses and identified alleles that may be added to existing repositories of the genetic database. [ABSTRACT FROM AUTHOR]

Case C‑205/21 VS v Ministerstvo na vatreshnite raboti, Glavna direktsia za borba s organiziranata prestapnost, Judgment of the Court of Justice of the European Union of 26 January 2023 The Court of Justice of the European Union (CJEU) decided that the systematic collection of biometric and genetic data of any accused individual in order for them to be entered in police records in an indiscriminate and generalised manner is not in compliance with the Union law. After summarising the judgment, this case note first questions whether the CJEU misclassified the personal data in question as genetic data. Then, it points out that the condition enshrined in Article 10 of the Law Enforcement Directive that allows sensitive data processing by law enforcement authorities only where strictly necessary is considered by the CJEU as a specific manifestation of lato sensu proportionality assessment. Considering that law enforcement authorities in the EU rely more and more on (biometric) technologies to prevent and fight against crimes, it concludes by speculating on some of the potential implications of this interpretation. [ABSTRACT FROM AUTHOR]

A study published in Nature by Matt Nelson and colleagues provides evidence that human genetics is crucial for improving the success rates of drug development. The study found that less than 10% of drugs that enter clinical development succeed, resulting in high costs for drug developers. Drugs often fail due to lack of efficacy or adverse effects, which can be better understood through human genetics. By including human genetics evidence in the decision-making process, drug companies can double their success rate from 10% to 20%. The study also highlights the need for continued investment in human genetics research to further improve drug success rates. However, it is important to note that the identification of an association between a gene and a disease does not necessarily mean that the gene is a good drug target. The study has some limitations, such as hindsight and selection biases, but real-world experiences of drug companies implementing genetics-based drug target prioritization may offer further confirmation of the impact of human genetics on clinical success. [Extracted from the article]

This article, published in the Egyptian Journal of Medical Human Genetics, discusses the identification of a novel ATR-X mutation in a myelofibrosis patient. ATR-X mutations have been associated with the onset of α-thalassemia in various hematological malignancies. The ATRX gene encodes a chromatin remodeling protein that regulates chromatin structure and function. The mutation identified in this study leads to a missense mutation in the PHD-like domain of the ATRX protein. The authors classified this mutation as potentially pathogenic based on computational predictions and its location in a mutational hot-spot region. This report contributes to the understanding of the ATRX gene mutational spectrum and may improve genetic screening and diagnosis of rare diseases. [Extracted from the article]

Background: Isolated growth hormone deficiency (IGHD) is a hereditary disorder that causes significant short stature. GHD has a reported incidence of 1/4000–1/10,000 births. It is caused by mutations in the major somatotroph axis genes, involving GH1, codes for growth hormone, GHSR, and GHRHR, codes for growth hormone secretagogue receptor and growth hormone-releasing hormone receptor, respectively. Aims of the study: The present study aims to examine the clinical phenotype and investigate the genetic etiology of ten Egyptian patients with type I isolated growth hormone insufficiency. Patients and methods: Patients recruited for the study were clinically diagnosed by two provocation tests and were subjected to a thorough history, clinical examination, and anthropometric measurements. Sanger sequencing and mutational analysis of the three genes, GH1, GHSR, and GHRHR, was our approach, performed in all enrolled IGHD patients. The variants identified were analyzed using the biological, population, sequence variants, and clinical genetics databases. Prediction of the pathogenicity of the novel variants was done by in silico prediction tools following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Sanger sequencing revealed a previously reported pathogenic mutation (NM_000823.4: c.1069C > T; p.Arg357Cys) in the GHRHR gene in one patient and a novel frameshift variant (NM_198407.2: c.1043dup; Ser349Leu fs*6) in the GHSR gene in another patient. This is the fourth report highlighting the autosomal dominant inheritance of the GHSR mutation as a cause of isolated growth hormone deficiency. A number of previously reported variants, but of rare frequency, were identified in this study. In our IGHD cases, 90% of the patients were underweight, 50% had anemia, and 80% showed hypovitaminosis D. Conclusion: Our findings broaden the mutational spectrum underlying the IGHD in Egyptian patients and point out the importance of mutation screening of the GHSR and GHRHR genes. This study also acknowledges the autosomal dominant mode of inheritance of the GHSR mutation as a cause for dwarfism. [ABSTRACT FROM AUTHOR]

Cork oak (Quercus suber L.) is an essential species of the Mediterranean region. In Morocco, it represents a source of life and is a noble species for many populations. The Maâmora forest, situated in Morocco, is recognized as the largest forest in the Mediterranean basin and displays the highest diversity compared to other forests in its distribution area. This study aimed to establish a genetic database of 240 individuals from Maâmora forest using seven SSR markers. Through a series of statistical analyses, we determined the level of diversity and genetic structure and created a core collection. Statistical analysis of the data showed a high degree of allelic variation, generating 47 alleles with an average of 6.71 alleles per locus. Furthermore, a high percentage of polymorphisms and a high Shannon index were observed. Intra-population genetic diversity was found to be high (86%) compared to inter-population diversity (14%). A low level of genetic differentiation (Gst = 0.12) and high gene flow were identified, consistent with the results obtained from the analysis of molecular variance (AMOVA). This suggests a possible capacity for the species to adapt to environmental conditions. A core collection of 18 genotypes was constructed, which included all the private alleles that were detected in this study. This core collection exhibited similar and crucial diversity to that identified in the initial collection, as verified by a series of genetic diversity and structural analyses. This research advocates populations and individuals for further studies on adaptation in order to improve and conserve this valuable resource in the future. [ABSTRACT FROM AUTHOR]