Genes

Introduction: Depression is a pervasive global health issue, affecting millions worldwide and causing significant disability. Despite its prevalence, current diagnostic and treatment approaches often yield suboptimal outcomes. The complexity of depression, characterized by diverse causes and symptoms, highlights the urgent need for advanced diagnostic tools and personalized therapies. Biomarkers, particularly genetic and epigenetic depression biomarkers, offer promise in uncovering the biological mechanisms underlying depression, potentially revolutionizing its management. Aim: Primary aim: To identify biomarkers associated with depressive disorders, with a focus on genetic and epigenetic biomarkers. Secondary aim: To optimize the current classification of biomarkers associated with different types of depressive disorders, with a focus on genetic and epigenetic biomarkers. Methods: We integrated findings with strategic keywords extracted from relevant studies, conducting a thorough literature review across the Google Scholar, PubMed, and Web of Science databases. Lastly, final reference inclusion had stringent criteria: recent, diverse peer-reviewed articles in English, all study designs, ensuring up-to-date coverage of genetic and epigenetic depression biomarker research. Results: The review reveals the classification of genetic and epigenetic biomarkers in regard to the type of biomarker, the system of the human body it derives from, and the sampling entity. All of the findings show promise in diagnosing depression, with the potential of predicting treatment outcomes and guiding personalized therapeutic approaches. We defined the significant correlations between genetic and epigenetic biomarker profiles and clinical parameters such as symptom severity and treatment response, thereby enhancing diagnostic accuracy and guiding treatment strategies tailored to individual patient needs across diverse depressive subtypes and treatment responses. Conclusion: Identifying biomarkers associated with depressive disorders, with a focus on genetic and epigenetic biomarkers, represents a critical step toward improving diagnostic precision and treatment efficacy. By elucidating the complex biological underpinnings of depression, this study contributes to the development of targeted therapies that address the diverse needs of individuals affected by this debilitating group of disorders. Future research should focus on validating these genetic and epigenetic biomarkers in larger cohorts and clinical trials to facilitate their clinical implementation and enhance patient outcomes.

Background/Objectives: The Y chromosome is a crucial tool in forensic genetics due to its unique characteristics, such as its haploid inheritance and lack of recombination. Y-STRs (short tandem repeats on the Y chromosome) are widely used for identifying male genetic profiles in DNA mixtures, especially in sexual assault cases where high levels of female DNA hinder autosomal analysis. This study evaluates the applicability of Y-STRs in forensic investigations, addressing their limitations and the impact of advanced technologies, such as rapidly mutating Y-STRs (RM Y-STRs). Methods: A comprehensive literature review was conducted to analyze existing knowledge on the application of Y-STRs in sexual crimes. The study also examines the role of population databases, such as YHRD, in estimating haplotype frequencies and enhancing forensic reliability. Results: Y-STR analysis proves essential for male DNA identification in complex mixtures, with RM Y-STRs enhancing discriminatory power. However, limitations persist, particularly in cases involving closely related male lineages. The population database coverage remains insufficient in regions like Cape Verde, affecting forensic reliability. Case studies demonstrate Y-STR effectiveness in solving cold cases and sexual crimes, reinforcing the need for expanded databases and methodological advancements. Conclusions: Y-STRs play a fundamental role in forensic genetics, particularly in sexual assault investigations. Their integration with advanced sequencing technologies and expanded databases is critical for improving forensic accuracy. Ethical considerations regarding genetic data privacy and potential discrimination must be addressed through clear regulations and forensic best practices.

Background: Pekin ducks are well-known meat-type ducks, whereas Shaoxing ducks are bred for their egg-laying abilities. Growth and development of poultry species is well studied; however, very little is known regarding differences in intestinal gene expression between Pekin and Shaoxing ducks. Methods: To investigate intestinal differences between Pekin and Shaoxing ducks, we conducted transcriptome analysis on ileal and cecal tissues from five 42-day-old ducks per breed, raised under identical housing and feeding conditions to minimize environmental influences. Results: The results showed that a total of 379 differentially expressed genes (DEGs) with p < 0.05 and ∣log2FoldChange∣ > 1 were identified in the ileum when Pekin ducks were compared to Shaoxing ducks, among which 158 were upregulated and 221 were downregulated. Compared to Shaoxing ducks, a total of 367 DEGs with p < 0.05 and ∣log2FoldChange∣ > 1 were identified in the ceca of Pekin ducks, among which 204 were upregulated and 163 were downregulated. Among these DEGs, nine genes were reported to be associated with growth and metabolism, namely, P2RX6, KCNJ6, CASQ2, EHHADH, ACSBG1, ELOVL4, AIF1L, VILL, and FABP1. Functional enrichment analyses using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases indicated that the DEGs were significantly involved in pathways such as calcium signaling, unsaturated fatty acid biosynthesis, fatty acid degradation, and tryptophan metabolism. Conclusions: In conclusion, our study identified transcriptome differences in the intestines of meat-type and laying-type ducks, offering insights into the genetic basis of their growth and metabolic differences. Future studies should validate key genes and explore environmental influences on gene expression.

Background: Acyl-CoA oxidase (ACX), a ubiquitous eukaryotic enzyme, catalyzes the initial steps of fatty acid β oxidation and plays an important role in the biosynthesis of jasmonic acid (JA). At present, no studies have been reported on ACX family members of maize and their function in disease resistance. Objectives: This study aims to lay a foundation for clarifying the functions of ACX family genes in maize growth, development, and stress response by conducting a genome-wide identification of ACX family genes in maize, analyzing the expression characteristics of these genes in maize growth and development, hormone treatment and response to biotic and abiotic stresses, and exploring the functions of key genes in the maize disease resistance process through the use of mutants. Methods: ProtParam, TBtools, MEME, MEGA, and IBS tools were used to identify maize ACX family genes and analyze the physicochemical properties of their proteins, chromosome location, phylogenetic relationships among family members, conserved domains, conserved motifs, and cis-acting elements. Meanwhile, the expression patterns of maize ACX family genes in different tissues and their expression patterns under abiotic and biotic stresses were studied by using the data from the maize GDB database and qRT-PCR technology. Moreover, the mutants of ZmACX1, ZmACX3, ZmACX4, and ZmACX5 genes were obtained, and the disease resistance of the mutants was detected to further determine the functions of ACX genes in the maize disease resistance process. This study identified maize ACX family genes using bioinformatics methods. Results: We discovered that six ACX genes in the maize genome are distributed across four different chromosomes. Cluster analysis further classified these genes into three subfamilies. All maize ACX genes possess a conserved ACOX domain, and their promoter regions are enriched with cis-acting elements associated with heat stress and the plant hormone response. Under various tissue, biotic, and abiotic stress conditions, as well as treatments with methyl jasmonate (MeJA) and salicylic acid (SA), the expression levels of maize ACX family genes exhibited significant differences. Notably, the expression levels of ZmACX1, ZmACX3, ZmACX4, and ZmACX5 were significantly up-regulated following stress and pathogen infection, suggesting their involvement in maize growth, development, and disease resistance. To elucidate the function of these genes in maize disease resistance, the resistance of ZmACX1, ZmACX3, ZmACX4, and ZmACX5 mutants to Cochliobolus heterostrophus, Curvularia lunata, and Fusarium graminearum were further examined. The results revealed that compared to the wild-type B73, the lesion area of the mutants was significantly increased after inoculation with pathogens. This directly demonstrated the crucial role of these genes in maize resistance to C. heterostrophus, C. lunata, and F. graminearum. Conclusions: In summary, this study systematically identified maize ACX family genes, and thoroughly investigated their expression patterns and functions in maize disease resistance. Our findings provide valuable insights into the comprehensive understanding of the function and mechanism of maize ACX family genes.

Background: The interaction and co-evolution between the gut microbiome and the host play important roles in the host’s physiology, nutrition, and health. Diet is considered an important driver of differences in the gut microbiota; however, research on the relationship between the gut microbiota and diet in Asian elephants remains limited. Methods: In this study, we explored the gut microbiota structure and its relationship with diet in different populations of Asian elephants through metagenomic sequencing, combined with previously published dietary data. Results: This study found that the dominant gut microbiota of Asian elephants includes the phyla Bacillota (29.85% in BP, 22.79% in RC, 21.89% in SM, 31.67% in ML, and 33.00% in NGH), Bacteroidota (25.25% in BP, 31.44% in RC, 16.44% in SM, 25.73% in ML, and 23.74% in NGH), and Spirochaetota (3.49% in BP, 6.18% in RC, 1.71% in SM, 2.69% in ML, and 3.52% in NGH), with significant differences in the gut microbiota among different populations. Correlation analysis between the gut microbiota and diet revealed that dietary diversity did not directly affect the alpha diversity of the gut microbiota. However, specific food types might play a key role in shaping the gut microbiota structure by regulating the abundance of certain microbiota. Conclusions: This study reveals significant differences in the gut microbiota structure among different populations of Asian elephants and explores the impact of diet on the structure. The results provide foundational data for a deeper understanding of the gut microbiota structure of Asian elephants and offer important references for the scientific conservation and precise management strategies of this species.

Obesity is a medical condition influenced by many factors and manifested by the excessive accumulation of fat. It is well documented that oxidative stress plays a significant role in the development of obesity and its related diseases. The antioxidant system’s enzymes, such as catalase, superoxide dismutase, glutathione peroxidase, paroxonase, etc., play a significant role in maintaining the oxidant–antioxidant balance in living organisms. Genetic variants of antioxidant system genes may affect the antioxidant system and its efficacy, which can lead to increased oxidative stress and higher risk for the development of obesity and its comorbidities. This review is focused on genetic variants such as single nucleotide polymorphisms of some antioxidant enzymes, ROS generators and transcription factors, and their impact on increased oxidative stress and the development of obesity and medical conditions related to obesity, like insulin resistance and metabolic syndrome.

Background: Dyggve–Melchior–Clausen syndrome (DMC) is a rare autosomal recessive skeletal dysplasia characterized by dwarfism, coarse facial features, and intellectual disability. Caused by loss-of-function variants in the DYM gene, which encodes dymeclin, DMC is predominantly reported in consanguineous populations but remains poorly studied in South America. Methods: We report a 21-year-old Ecuadorian male with clinical features suggestive of DMC. Comprehensive clinical, radiological, and genetic evaluations were conducted, including clinical exome sequencing and Sanger sequencing, followed by an in silico analysis to assess the structural and functional consequences of the identified variant. Results: Exome sequencing identified a homozygous c.1878delA (p.Lys626fs) frameshift variant in the DYM gene, which was confirmed by Sanger sequencing as inherited from heterozygous parents. Variants of uncertain significance were detected in other skeletal dysplasia-related genes but did not correlate with the phenotype. A comprehensive review of reported DYM variants was also conducted. Conclusions: This report documents the first case of DMC in Ecuador and the second in South America, expanding the global understanding of DMC’s genetic diversity. It underscores the value of next-generation sequencing in rare disease diagnostics and highlights the critical need for inclusive genomic research in underrepresented populations to improve the understanding of genetic heterogeneity and rare disease epidemiology.

Background/Objectives: The resistance to occult mastitis in dairy cows is a multifaceted trait influenced by a variety of genetic and environmental factors, posing significant challenges to its prevention and treatment. Methods: In this study, a cohort of 389 Holstein dairy cows was selected for investigation. The genes NOD2, CXCR1, SPP1 and LF, which are implicated in resistance to occult mastitis, were genotyped utilizing the efficient and cost-effective Kompetitive Allele-Specific PCR (KASP) technology. Additionally, the study analyzed the association between various single nucleotide polymorphisms (SNPs) and the somatic cell score in Holstein dairy cows. Multi-locus penetrance variance analysis (MPVA) analysis was also conducted to assess the resistance of different genotypic combinations to recessive mastitis in dairy cows. A genotyping kit for occult mastitis resistance was developed. Subsequently, 300 Holstein cows were randomly selected to evaluate the accuracy of the kit’s classification and resistance detection. Results: The findings revealed that the most effective genotype combination was SPP1(AA)-CXCR1(CC)-NOD2(CA)-LF(GA). Upon verification, the genotyping kit for recessive mastitis resistance in dairy cows exhibited an accuracy rate of 100% for individual genotyping and 95.90% for resistance detection. Conclusions: From the perspective of disease resistance genetics, this study lays a foundation for the precise management of dairy cow herds. It enables the early identification and removal of individuals susceptible to subclinical mastitis, thereby improving the overall quality of the cattle population.

Background/Objectives: Schizothorax curvilabiatus, a typical highland polyploid species within the subfamily Schizothoracinae, holds economic value and ecological research significance. Currently, there are no related genomic studies. To obtain its genetic information and lay the foundation for subsequent whole-genome map construction, this study conducted a genome survey analysis, preliminary genome assembly, microsatellite identification, repeat sequence annotation, mitochondrial genome characterization, and phylogenetic relationship research. Methods: DNA was sequenced on a DNBSEQ-T7 platform to obtain paired-end genomic data. The genome was analyzed using GCE, and the draft genome was assembled with SOAPdenovo. Microsatellites were identified using MISA, and the mitochondrial genome was assembled with NOVOPlasty. Genome features were analyzed, and phylogenetic trees were constructed using PhyloSuite and MEGA. Results: The genome size was estimated at 2.53 Gb, with a heterozygosity of 6.55% and 47.66% repeat sequences. A 1.324 Gb preliminary genome draft was obtained, with repeat sequences comprising 47.17%, the majority being DNA transposons (24.64%). Dinucleotide repeats were most abundant (46.91%), followed by mononucleotide repeats (38.31%), with A/T and AC/GT being the most frequent. A complete mitochondrial genome of 16,589 bp was assembled, and a 939 bp D-loop was annotated. Phylogenetic relationships among genera in the Schizothoracinae subfamily were also clarified. Conclusions: This study provides the latest molecular data for analysis of the S. curvilabiatus genome and its related populations, and for the first time offers genomic resources for research on genomic adaptive evolution and polyploidization in high-altitude environments.

Background: High temperatures during the early generative stage significantly threaten maize productivity, yet the molecular basis of heat tolerance remains unclear. Methods: To elucidate the molecular mechanisms of heat tolerance in maize, two hybrids—ZD309 (heat-tolerant) and XY335 (heat-sensitive)—were selected for integrated transcriptomic and physiological analyses. The plants were subjected to high-temperature treatments (3–5 °C above ambient field temperature) for 0, 1, 3, 5, and 7 days, with controls grown under natural conditions. Physiological indices, including Superoxide dismutase (SOD) activity, and proline (PRO), malondialdehyde (MDA), soluble sugar, and protein content, were measured. Results: Transcriptome analysis identified 1595 differentially expressed genes (DEGs) in XY335 (509 up- and 1086 down-regulated) and 1526 DEGs in ZD309 (863 up- and 663 down-regulated), with the most pronounced changes occurring on day 5. Key DEGs in XY335 were enriched in galactose metabolism and carbohydrate catabolism, whereas ZD309 exhibited rapid activation of oxidative stress and cell wall integrity pathways. Mfuzz time-series analysis categorized DEGs from XY335 and ZD309 into six clusters each. Weighted gene co-expression network analysis (WGCNA) identified 10 hub genes involved in ubiquitin thioesterase activity and RNA modification, suggesting protein-level regulatory roles. Conclusions: This study reveals distinct transcriptional dynamics between heat-tolerant and heat-sensitive varieties, providing candidate genes for breeding thermotolerant maize and advancing our understanding of heat stress responses during critical reproductive stages.

Background: Chicken Primordial Germ Cells (PGCs) are one of the few germ cells that can be cultured for a long time in vitro, but challenges remain such as low culture efficiency and unclear roles of nutrient factors and signaling pathways. Method: In this study, protein kinase B (AKT) pathway activator insulin-like growth factor 1 (IGF-1) was screened for its ability to promote cell proliferation by transcriptome results using various inhibitors of pathway activation. The effects of IGF-1 on PGCs were evaluated through EdU assays, qRT-PCR, flow cytometry, and migration experiments. Results: This study systematically examined the effects of insulin and IGF-1 on the proliferation, cell cycle, ferroptosis, migration capacity, and establishment efficiency of PGCs. The findings demonstrated that IGF-1 exhibited comparable effects to insulin and could effectively replace insulin in PGC culture systems. Conclusions: The research results are expected to provide a solid theoretical basis for optimizing the chicken PGC cultivation system and promoting its practical application.

Background/Objectives: Taxonomic profiling of soil microbial communities is useful for assessing and monitoring the biological status of agricultural land. In this study, we aimed to investigate changes in the taxonomic structure of soil organisms in minimally managed agricultural fields. Methods: We used DNA metabarcoding to investigate both terrestrial prokaryotes and eukaryotes in cabbage-cultivated and uncultivated sites in a minimally managed agricultural field in central Japan from February to August 2021. Analyses of the relative abundances of prokaryotic and eukaryotic sequence variants (SVs) and their β-diversities, and the subsequent redundancy analysis (RDA) clarified the dynamic changes in eukaryotic communities during cultivation. We further investigated taxonomic changes in fungi-, protist-, and animal-derived SVs, abundant SVs in each eukaryotic phylum, as well as the co-occurrence networks of the top 150 SVs. Results: The results revealed that the fractions of predatory or parasitic protists and animals increased, whereas those of fungi and earthworm Enchytraeus spp. decreased. The fractions of abundant SVs derived from diatoms, Ciliophora, the class Vampyrellidae (Cercozoa), and mites increased and subsequently decreased during this period. These findings suggest that predatory protists and animals fed on bacteria and autotrophic eukaryotes (such as diatoms) propagated in spring, followed by their propagation and parasitism to host eukaryotes. The networks also changed, especially prokaryotic networks that markedly changed from April to May, and those of eukaryotes from May to June–August, supporting the observations mentioned above. Conclusions: These findings indicate the dynamic and sequential changes in soil communities in fields with minimal agricultural practices and could be useful for sustainable natural farming.

Background: The aim of this study was to develop a genetic transformation system to construct an overexpression vector for the mitochondrial gene atp6 in tobacco, thereby providing a foundation to investigate the functional roles of mitochondrial genes in this species. Methods: A full-length coding sequence (CDS) of the atp6 gene from a sterile line was cloned, along with the mitochondrial leader peptide sequence of atp2-1 from tobacco, using cDNA from kenaf UG93A anthers as a template. An overexpression vector for plants was constructed by employing In-Fusion technology, and wild-type tobacco plants were transformed via Agrobacterium-mediated transformation. Transgenic tobacco plants were then subjected to resistance screening and PCR validation. Results: The overexpression vector PBI121-atp2-1-atp6-EGFP, which includeds the mitochondrial leader peptide sequence, was successfully constructed. PCR validation using two pairs of primers targeting different sites on the overexpression vector confirmed the stable expression of the target gene in six transgenic tobacco plants (H1, H3, H4, H5, H7, and H8) via both primer pairs. A phenotypic analysis and iodine‒potassium iodide (I₂-KI) staining of pollen grains from transgenic tobacco plants revealed the presence of shriveled and malformed pollen grains with reduced viability. These findings suggest that the atp6A gene, including the mitochondrial signal peptide, induces pollen abortion in tobacco. Conclusions: The genetic transformation system developed for the vector overexpressing the atp6 mitochondrial gene from kenaf provides a valuable framework to investigate the molecular regulatory mechanisms underlying the role of the atp6 gene in kenaf cytoplasmic male sterility (CMS).

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that first develops in early childhood and is characterized by restricted interests, activities, and behaviors, as well as difficulties with social interactions and communication. ASD arises from a complex interaction between environmental factors and genetic inheritance, influenced by epigenetic mechanisms. With an estimated heritability of 70–90%, ASD is highly familial, indicating that genetic factors play a significant role in its development. This shows how hundreds of genetic variants contribute to ASD, whose risk effects are highly variable and are often related to other conditions; these genetic alterations are at different levels, which include single gene mutations, monogenic disorders, genomic variants, and chromosomal abnormalities. Copy number variants (CNVs) appear to contribute significantly to understanding the pathogenesis of this complex disease. In some cases, single CNVs in genomic DNA are pathogenic and causative, supporting the hypothesis that some sporadic cases of ASD may result from rare mutations with significant clinical impact. However, in many cases, there are common genomic variants that increase the risk of developing ASD but are insufficient by themselves to determine an ASD phenotype, and rare genomic variants, of various sizes, inherited from a parent or de novo, that can be associated with the ASD phenotype. Therefore, the aim of this review is to deepen the concept of ASD inheritance through the two-hit theory of CNVs, in which the concomitant presence of two alterations could determine the clinical phenotypes, the concept of incomplete penetrance for inherited CNVs with pathogenic clinical significance, and the presence of compound heterozygosity. These aspects represent important mechanisms underlying the pathogenesis of autism, contributing to a better elucidation for the understanding of the genetic contribution to the ASD phenotype.

Background: Coptis chinensis is a traditional medicinal plant rich in bioactive compounds like berberine, known for its antibacterial, anti-inflammatory, and antioxidant properties. This study aims to analyze the MYB transcription factor family in C. chinensis to better understand their roles in plant growth, development, metabolism, and stress responses. Methods: We employed bioinformatics to conduct a genome-wide identification of MYB genes in C. chinensis, followed by analyses of physicochemical properties, phylogenetic relationships, gene structures, chromosomal localization, conserved motifs, cis-acting elements, and expression patterns. Results were validated using qRT-PCR. Results: A total of 129 CcMYB genes were identified across nine chromosomes. Phylogenetic analysis categorized these genes into 19 subgroups, notably highlighting the S6 subgroup, which lacks counterparts in Arabidopsis. Comparative genomics revealed segmental duplication among gene pairs. Transcriptomic analysis indicated that CcMYB21, CcMYB40, CcMYB105, and CcMYB116 had high expression levels in stems. Importantly, CcMYB94 expression significantly increased under cadmium stress, suggesting its role in stress regulation. Conclusions: This study offers a comprehensive analysis of the MYB gene family in C. chinensis, underscoring the significance of MYB transcription factors in enhancing the plant’s medicinal value and stress tolerance, particularly against cadmium exposure. These insights pave the way for further exploration of specific MYB genes to improve stress resilience in C. chinensis.

Background: Two hereditary eye disorders that are frequently observed in Collies and related breeds are Collie Eye Anomaly (CEA) and Progressive Retinal Atrophy (PRA). The main symptom of CEA is choroidal hypoplasia. It is associated with a 7.8 kb deletion in intron 4 of the NHEJ1 gene located on chromosome CFA7. Rod–cone dysplasia 3 (RCD3), an early-onset form of PRA, is associated with mutations in the PDE6A gene. Methods: Molecular diagnostic techniques were used in this study to identify genetic mutations linked to CEA and RCD3-type PRA in a subset of dog breeds. Australian Shepherds (n = 29), Border Collies (n = 9), Longhaired Collies (n = 27), and Shetland Sheepdogs (n = 10) provided a total of 75 DNA samples. Samples were collected by buccal swab or blood draw, and PCR and real-time PCR methods were used for processing. Results: Of the dogs in the studied breeds, 31 had the NHEJ1 gene mutation linked to CEA. Among these, 15 were homozygous recessive (affected), while 16 were heterozygous (carriers). None of the samples had any mutations in the PDE6A gene associated with RCD3-type PRA. Conclusions: Effective identification of carriers and affected individuals for CEA was made possible by PCR-based genetic testing, confirming its value in early diagnosis and breed control. Although the RCD3 form of PRA has not been previously reported in Collies or Australian Shepherds, it was included in our analysis due to the genetic relatedness among herding breeds and the potential presence of undetected carriers resulting from historical crossbreeding.

Background/Objectives: According to the International Classification of Hereditary Skeletal Diseases (2019), osteogenesis imperfecta (OI) is classified as a disorder resulting from impaired formation of the cortical layer density of diaphyses and metaphyseal modeling. OI comprises a heterogeneous group of genetic diseases, with most cases inherited in an autosomal dominant manner, while others follow autosomal recessive or X-linked recessive inheritance patterns. Accurate DNA testing is essential for precise medical and genetic counseling, ensuring reliable prognostic assessments for patients’ descendants and siblings. As part of a medical genetic study of the population of the Republic of the North Ossetia Alania, specifically in the Mozdok district, specialists from the Laboratory of Genetic Epidemiology at the Research Centre for Medical Genetics (RCMG) examined a family with 13 affected individuals with OI across four generations. Methods: A comprehensive clinical assessment was performed, followed by molecular genetic analysis using whole-exome sequencing (WES). Segregation analysis within the family was conducted via Sanger sequencing. Results: Clinical evaluation suggested a diagnosis of OI, which was subsequently confirmed by genetic testing. The severity and spectrum of symptoms varied considerably among affected family members and were influenced by age and specific nuclear family lineage. Molecular analysis in the proband identified a heterozygous pathogenic variant in the COL1A1 gene variant (c.1243C>T, p.(Arg415*)), confirming a diagnosis of OI type IV. The variant was found to co-segregate with the disease within the family. Conclusions: Molecular diagnosis enabled precise risk assessment for affected offspring in family members with mild phenotypic manifestations. Additionally, pediatric patients were referred for standard bisphosphonate therapy to manage the condition effectively.

Background: Glioblastoma is a highly aggressive brain tumour with poor survival outcomes, highlighting the need for reliable prognostic models. Developing robust and interpretable prognostic signatures is critical for improving patient stratification and guiding therapy. This study explored the integration of machine learning feature selection with regularised Cox regression to construct prognostic gene signatures for glioblastoma patients. Methods: We combined the Boruta algorithm and Random Survival Forests (RSFs) with regularised Cox regression, along with network-based regularisation techniques (HubCox and OrphanCox), to develop interpretable prognostic signatures for stratifying high- and low-risk glioblastoma patients. Using mRNA-seq and survival data from The Cancer Genome Atlas (TCGA), we developed predictive models following WHO-2021 glioma guidelines. Results: Integrating Boruta or RSF with regularised Cox regression improved the performance and interpretability. Boruta increased the concordance indexes (C-indexes) by 0.030 and 0.013 for LASSO and Elastic Net, respectively, while significantly reducing the feature numbers. RSF similarly enhanced the performance and feature reduction. The genes Lysyl Oxidase Like 1 (LOXL1) and Insulin Like Growth Factor Binding Protein 6 (IGFBP6) were consistently selected and linked to glioma survival, emphasising their clinical significance. The network-based methods demonstrated superior survival probability prediction (lower Integrated Brier Score), although with lower C-index values, highlighting limitations in ranking the survival times. To evaluate the generalisability, external validation using the Chinese Glioma Genome Atlas (CGGA) confirmed that a multigene signature derived from the most consistently selected genes significantly stratified the patients by risk. Conclusions: This study underscored the utility of combining machine learning feature selection with survival analysis to enhance prognostic modelling while balancing predictive performance and interpretability.

Background: The RSPO gene family encodes secreted glycoproteins that are rich in cysteine, which generally serve as activators of the Wnt signaling pathway in animals. Four types of this family have been identified in a few model species. However, the evolution of the family remains unclear. Methods: In this study, we identified a total of 1496 RSPO homologs through an extensive survey of the RSPO genes in 430 animals. Gene family clustering and phylogenetic analysis identified four major subtypes of the family (RSPO1-RSPO4) and clarified their distribution of copy number in different species. Results and Conclusions: Members of the RSPO4 subfamily that were closest to ancestral forms existed in both Deuterostomes and Protostomates, and we speculate that representatives of this subfamily already existed in Urbilatera, the last common ancestor of Deuterostomes. Particularly, in some RSPO3 subtypes of Actinopterygii (ray-finned fishes), an FU repeated motif with three conserved cysteines was identified. Further conservative analysis of amino acids and alignment of tertiary protein structure revealed the potential functional sites for each subgroup. The results provide insight into the phylogenetic relationships and evolutionary patterns of conserved motifs of RSPO family genes in animal kingdoms, which will guide further studies on the biological functions of RSPO in other non-model species.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, affecting approximately 1 in 1000 individuals. This genetically heterogeneous condition is primarily caused by monoallelic pathogenic or likely pathogenic variants in the PKD1 and PKD2 genes, accounting for 78% and 15% of typical cases, respectively. Recently, the application of NGS methods has led to the identification of additional genes associated with ADPKD, which have been incorporated into routine diagnostic testing for detecting phenocopies of the disease. Methods: In this study, targeted NGS (tNGS) analysis of the main cystogenes associated with classic and atypical ADPKD was performed in a cohort of 218 patients clinically diagnosed with cystic nephropathies. Results: Genetic testing identified variants in 175 out of 218 cases (80.3%). Among these, 133 probands (76%) harbored likely pathogenic or pathogenic variants in one or more genes of the panel, while 42 individuals (24%) had a variant of unknown significance (VUS). Specifically, one or more class 4/5 variants in PKD1, PKD2, or both were identified in 111 (83.5%) probands. Remarkably, a pathogenic variant in the IFT140 gene was identified in 14 index cases (8% of positive individuals, 6.4% of the global cohort): 10 distinct loss-of-function (LoF) variants were identified (including four frameshift variants, four nonsense variants, and two splice site defects); one individual carried a second IFT140 missense variant classified as VUS. Furthermore, five affected family members were found to carry a P/LP LoF variant in IFT140. Conclusions: Our data support that IFT140 heterozygous IFT140 LoF variants result in an atypical, mild form of ADPKD, consisting of bilateral kidney cysts and renal functional decline at older ages. Furthermore, we describe the second pediatric patient with a mild form of ADPKD due to an IFT140 variant and discuss hyperuricemia as a previously unappreciated feature of this condition.

Background/Objectives: Hatchery fumigation is recognized as a crucial step to control microbial bloom in the environment, and formaldehyde is one of the most widely used disinfectants to ensure successful hatchability and healthy production. While many of the benefits are thought to be derived from disinfectant properties, it is possible that additional host gene and genetic pathway modulation could contribute to these outcomes. The current study aimed to capture the in ovo transcriptional response of liver tissue to formaldehyde treatment. Methods: Chick embryos were subjected to formaldehyde fumigation treatment for 25 min at 24–25 °C and 75% relative humidity, keeping a control group as untreated. On the 18th day of incubation at 37.8 °C and 58–63% humidity, eggs were broken, and liver tissue was obtained for RNA isolation, cDNA library preparation, and RNA sequencing. Results: Bioinformatics analysis revealed 908 significant differentially expressed genes (DEGs), among which 814 were known genes and 94 were novel genes. A total of 672 DEGs were upregulated, whereas 236 genes were downregulated in response to FA treatment. Of the 94 novel genes, 80 were upregulated. Key DEGs, associated QTLs, and transcription factors were involved in immuno-inflammatory responses, oxidative stress, epigenetic modification, and cellular adaptation-related activities. Further research should focus on biological validation of key DEGs to clarify their roles, pathways, and relationships to FA treatment. Conclusions: Overall, these findings (1) provide critical molecular detail as a first step towards genetic selection to improve formaldehyde treatment response and effectiveness, and (2) provide DEG signatures for FA treatment as a reference against which to compare other interventions to achieve hatchability and production benefits.

Background: Functional alleles of host plant susceptibility genes (S genes) can exacerbate the severity of diseases by enhancing pathogen compatibility. Genetic editing of the targeted host S genes has demonstrated remarkable efficacy in conferring broad-spectrum resistance across multiple crop species. We have previously identified a Golgi-localized Nucleotide Sugar Transporter 1 homolog (SlGONST1.1) in the host plant Solanum lycopersicum as a susceptibility gene towards late blight caused by Phytophthora infestans. Methods: In this study, we performed a detailed characterization of tissue-specific and P. infestans-inducible expression patterns of this gene, and the subcellular localization of its encoded protein product. Results: Similar to phenotypes of two reported Slgonst1.1 edited lines, two newly generated genetically edited lines of SlGONST1.1 demonstrated enhanced resistance against P. infestans without obvious growth and developmental abnormality. Phytohormonal quantifications and reactive oxygen species measurements showed that an Slgonst1.1 line had lower constitutive abscisic acid contents and depleted reactive oxygen species burst induced by pathogen-associated molecular pattern. Further comparative transcriptomic analyses revealed that the expression of defense-related genes is disproportionally up-regulated in the Slgonst1.1 line. Conclusions: In summary, our findings confirmed SlGONST1.1 as a functional host susceptibility gene towards late blight and shed light on the potential molecular mechanism underlying its function.

Background: Macrocephaly can be a component manifestation of several monogenic conditions, in association with intellectual disability/developmental delay (ID/DD) behaviour abnormalities, including autism spectrum disorders (ASD), and variable additional features. On the other hand, idiopathic ASD can present with developmental delay and macrocephaly. Methods: We carried out a retrospective analysis of a cohort of 78 patients who were tested from February 2017 to December 2024 by high-throughput sequencing of a panel of 27 genes (ABCC9, AKT1, AKT2, AKT3, BRWD3, DIS3L2, DNMT3A, EZH2, GPC3, GPC4, HERC1, MED12, MTOR, NFIA, NFIX, NSD1, PDGFRB, PIK3CA, PIK3R1, PIK3R2, PPP2R1A, PPP2R5D, PTEN, RAB39B, RNF135, SETD2, and TBC1D7) because of neurodevelopmental impairment, including ID/DD, ASD/behaviour abnormalities associated with macrocephaly, mimicking to a large extent idiopathic ASD. Results: Pathogenic variants leading to the diagnosis of monogenic conditions were detected in 22 patients (28%), including NSD1 (2), PTEN (16), and PPP2R5D (4). Distinctive of the PTEN-associated phenotype were true macrocephaly (100%), ASD or behaviour abnormalities (92%), mild/borderline ID (79%), and no facial dysmorphisms. Typical of the PPP2R5D-associated phenotype were relative macrocephaly (75%), a few unspecific peculiar facial characteristics (50%), and a more variable presentation of the neurodevelopmental phenotype. Conclusions: Pathogenic variants in PTEN and PPP2R5D are the most recurrent gene mutations in a patient-oriented procedure for the genetic diagnosis of apparently idiopathic ASD and behaviour abnormalities associated with macrocephaly. The clinical applicability of the presented diagnostic strategy is discussed.

Background: Splenic B-cell lymphomas and leukaemias include hairy cell leukaemia, splenic marginal zone lymphoma, splenic diffuse red pulp small B-cell lymphoma, and splenic B-cell lymphoma/leukaemia with prominent nucleoli. The main diagnostic challenge is to differentiate between splenic B-cell lymphomas and leukaemias due to highly overlapping clinical, morphologic, and phenotypic features in the absence of splenectomies for diagnostic purposes. Case presentation: We describe a case of a 78-year-old woman who presented with weight loss and was subsequently found to have pancytopenia, lymphocytosis, and splenomegaly. Peripheral blood smear showed a homogenous population of small- to medium-sized lymphocytes having oval nuclei, condensed chromatin, and villous cytoplasmic projections. Bone marrow showed B-cell infiltrate in a predominantly intrasinusoidal pattern. Except for cyclin D1 and BRAF, the immunophenotype was similar to that of hairy cell leukaemia. This was further supported by the lack of BRAF p.V600E mutation by polymerase chain reaction. A diagnosis of splenic diffuse red pulp small B-cell lymphoma was thus favored based on the lack of cyclin D1 expression and pattern of infiltration in the bone marrow biopsy. Conclusions: Awareness of this infrequent clinical presentation and immunophenotype of splenic diffuse red pulp small B-cell lymphoma is crucial for diagnosis and devising appropriate therapeutic strategies for the patient.

Background/Objectives: Grapes (Vitis vinifera), particularly ‘Shine Muscat’, are prone to postharvest quality loss mainly due to poor storage tolerance. Actinomycetes are microbial resources that produce secondary metabolites that exhibit notable functional properties. Methods: This study explored the use of Streptomyces albulus Ah11601 fermentation broth (SFB) as a postharvest treatment to preserve ‘Shine Muscat’ grape quality during 6 days of room temperature storage using physiological, transcriptomic, and bioinformatics analyses to elucidate the underlying regulatory mechanism. Results: The results demonstrated that, compared to the control group stored at room temperature (25 °C) for 6 days (6D), the SFB-treated group (T6D) presented a significant delay in the decrease in fruit hardness and vitamin C content. Further investigations revealed that the 6D treatment significantly elevated lipoxygenase activity, MDA content, O2⁻ generation rate, and H2O2 levels. In addition, both the 6D and T6D treatments significantly increased the activities of SOD and APX. Functional enrichment analysis revealed that the upregulated DEGs in the 6D group were predominantly enriched in pathways such as phenylpropanoid biosynthesis; flavonoid biosynthesis; phenylalanine metabolism; and stilbenoid, diarylheptanoid, and gingerol biosynthesis. The downregulated DEGs were enriched primarily in the endoplasmic reticulum protein processing pathway. In the T6D group, the upregulated DEGs were predominantly enriched in the zeatin biosynthesis pathway. In addition, significant alterations in the expression of genes associated with the ethylene and abscisic acid signaling pathways were detected. Conclusions: In conclusion, SFB treatment effectively mitigated the deterioration of the postharvest quality of ‘Shine Muscat’ grapes by preserving the cellular redox balance, regulating cytokinin and ethylene biosynthesis, and optimizing the regulation of ethylene and abscisic acid signaling.