Frontiers in Genetics最新文献

Polycystin-1 (PC1), encoded by the PKD1 gene, forms a complex with polycystin-2 (PKD2; 173910) that regulates multiple signaling pathways to maintain normal renal tubular structure and function. Mutations in the PKD1 gene are the primary cause of type 1 PKD (polycystic kidney disease), accounting for 78%-85% of all PKD cases. In this study, we report a case of a boy presenting with microscopic hematuria with multiple renal cysts and carrying an unreported intronic variant, c.12445-34_12445-10del, in the PKD1 gene inherited from his father who also presented PKD. Sanger sequencing and reverse transcription polymerase chain reaction (RT-PCR) for minigene splicing assays showed two abnormal splicing alterations with the c.12445-34_12445-10del variant at the mRNA level: one causes a 16-bp deletion in exon 46, resulting in premature protein termination (p.Phe4149GlyfsTer45), and the other results in a 205-bp deletion, leading to delayed termination (p.Phe4149ProfsTer139). Based on the clinical characteristics and gene mutations with functional verification, the patient was finally diagnosed with PKD caused by PKD1 function defection, as confirmed by the combined clinical features and genetic analysis. Management strategies include dietary management, blood pressure monitoring, and regular follow-up of kidney function. This is the first study to report an intronic deletion in the PKD1 gene that influences alternative splicing. Our findings expand the mutation spectrum leading to PKD1-related diseases and highlight the importance of genetic counseling for the family.

Introduction: A novel set of pyramided lines for durable blast resistance was developed using marker-assisted backcross breeding (MABB) strategy in the genetic background of the aromatic landrace Mushk Budji (MB).

Methods: Simultaneous-but-stepwise transfer of the blast resistance genes Pi54 and Pi9 was achieved through the integration of foreground selection (FS) and background genome recovery processes, aided by genome-wide SSR and >1500 KASP markers. MABB, whole genome re-sequencing, coupled with stringent phenotypic selection for aroma, amylose content, kernel dimensions, and cooking quality, helped minimize the linkage drag and achieve early recurrent parent genome (RPG) recovery in the inter-cross BC₂F_2:3 generation.

Results: The two-gene lines carrying Pi9 + Pi54 were developed through inter-crossing corresponding near-isogenic lines (NILs) with an RPG of approximately 90%. With the help of sequencing of the derived NILs, we were able, for the first time, to establish the role of major alleles underlying rice quality and stress resilience in MB. In the process, we confirmed the retention of favorable alleles at key genetic loci, such as BADH2 (aroma), Wx (amylose content), Rc (white pericarp), Hd1/Hd4/Hd5 (heading date), and COLD1/COLD6 (cold tolerance) in the derived NILs. GGE biplot analysis revealed stable performance of five advanced lines across target ecologies.

Discussion: The set of NILs was useful in elucidating the phenotypic effects of 11 genes related to grain type, quality, and adaptability traits in the landrace MB. Multi-environment screening for blast resistance, at hot spot locations, in addition to artificial inoculation, validated the resistance response of the lines to both leaf and neck blast. This study demonstrates the successful integration of genomics-assisted breeding and phenotypic selection to improve a heritage rice variety for enhanced disease resistance and ecological adaptation. The development of improved MB lines represents a rare endeavor towards the area expansion and conservation of the heirloom rice.

Introduction: Coronary atherosclerotic heart disease (CHD) is a leading cause of morbidity and mortality worldwide, making timely identification critical for improving patient prognosis. However, traditional imaging examinations are limited by high costs and patient selection bias, while existing prediction models often lack interpretability and generalization ability. This study aimed to develop a robust, interpretable machine learning approach to address these challenges.

Methods: This retrospective study analyzed hospitalized patients at Quzhou People's Hospital from July 2021 to March 2025. Patients diagnosed with CHD were categorized as positive samples, while those without cardiovascular disease served as negative controls. The dataset integrated demographic data, blood biomarkers, and vital signs. A Generative Adversarial Imputation Network (GAIN) was utilized to handle missing values, and multiple machine learning models were constructed and compared for prediction performance.

Results: Among the evaluated algorithms, the XGBoost model achieved superior performance on the test set with an Area Under the Curve (AUC) of 0.9053. To enhance clinical utility, the integration of SHAP (SHapley Additive exPlanations) values enabled both global and local interpretation of model decisions. Key predictive factors identified included mean respiratory rate during hospitalization, age, high-sensitivity troponin I (hs-cTnI), and hypertension.

Discussion: The developed model demonstrates robust prediction performance combined with high clinical interpretability. Unlike traditional "black box" models, this approach clarifies the contribution of specific risk factors. Crucially, the tool is well-suited for dual deployment: serving as an automated screening tool integrated into hospital electronic health records (EHRs) and as a self-monitoring aid for individuals with underlying health conditions via mobile health applications.

Cancer progression involves dynamic crosstalk between tumor-intrinsic pathways and microenvironmental remodeling, and identifying pan-cancer biomarkers is critical for precision oncology. CDKN2AIPNL exhibits a paradoxical role in cancer, acting as a tumor suppressor in myeloid malignancies but promoting solid tumor progression, yet its systematic pan-cancer characteristics remain unelucidated. This study aimed to comprehensively analyze CDKN2AIPNL's expression patterns, prognostic value, genetic alterations, and molecular mechanisms across multiple tumor types using public datasets including TCGA, GTEx, HPA, and tools such as GEPIA2, cBioPortal, TIMER2, STRING, and BioGRID. We performed expression difference analysis, survival analysis (overall survival, disease-free survival, progression-free survival), genetic alteration analysis, cancer-associated fibroblast (CAF) infiltration analysis, and gene/protein interaction enrichment analysis. Results showed that CDKN2AIPNL was significantly upregulated in multiple tumors (e.g., LIHC, UVM, BRCA, LUAD) and downregulated in others (e.g., KICH, KIRP, THCA), with high tumor specificity. Elevated CDKN2AIPNL expression correlated with poor overall survival in LIHC (HR = 1.7, p = 0.0026), UVM (HR = 26, p = 2.2e-6), BRCA (HR = 26, p = 2.2e-6), LUAD (HR = 1.36, p = 0.049), PCPG (HR = 1.71, p = 0.0012), and TGCT (HR = 0.37, p=0.023), and was associated with advanced tumor stages in metabolically active cancers. Genetic alterations (amplifications and mutations) were frequent in KIRC (>5%) and ACC (>4%), with all mutations localized to the XTBD region, and amplification predicted poor prognosis in PRAD (p = 0.008) while mutations conferred favorable outcomes in BLCA. CDKN2AIPNL expression positively correlated with CAF infiltration in ESCA, KICH, UVM, and other tumors, and interacted with MYC, XRN2, and CHAMP1 to regulate metabolic reprogramming, cell cycle, and immune suppression. Our findings systematically reveal CDKN2AIPNL's dual role in tumorigenesis and validate it as a potential pan-cancer prognostic biomarker, providing novel insights for cancer diagnosis and targeted therapy.

The mitochondrial genome provides crucial information for understanding the evolution and phylogeny of various Apis cerana populations. Apis cerana-Southern China is a unique ecological type of Asian bee, A. cerana, primarily found in the coastal mountains of South China. Here, we used PacBio-HiFi sequencing to obtain the complete mitochondrial genome of A. cerana-Southern China and infer the phylogenetic relationships between A. cerana-Southern China and other A. cerana ecotypes. The mitochondrial genome of A. cerana-Southern China contains 16,137 bp and includes 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes, and an AT-rich region. The overall base composition is as follows: A (42.41%), C (9.59%), G (6.18%), and T (41.82%). The combined percentage of A and T (84.23%) is significantly higher than that of G and C. Among the 37 genes, 23 were located on the majority strand, while the remaining 14 were located on the minority strand. The phylogenetic tree based on the 13 PCGs showed that the genetic distance between A. cerana-Southern China, A. cerana-Central China, and A. cerana-Aba was closer. The complete mitochondrial genome sequence reported here would be useful for further phylogenetic analysis and conservation genetic studies in A. cerana-Southern China.

The major histocompatibility complex (MHC) is the central genetic basis of adaptive immune responses, it plays a crucial role in antigen presentation, immune surveillance, and susceptibility to various diseases. Therefore, accurate MHC identification is essential for both immunological research and clinical applications. Most existing methods still depend on manually engineered features or a single protein language model (PLM for short), these methods cannot perfectly capture complementary information across sequence lengths or across different PLMs. Furthermore, most existing methods often adopt conventional machine learning algorithms or simple multilayer perceptron (MLP) classifiers to construct identification model, they have no ability to model deep semantic dependencies within sequences. To overcome these limitations, we introduce an MHC identification model based on dual-stage training and multi-view feature fusion, termed DFL-MHC, a novel framework that unifies multi-sequence and multi-model views within a dual-stage training strategy. In the feature extraction stage, we design a cross-sequence and cross-model multi-view scheme. In this scheme, a protein sequence is truncated into two different residue sequences with a length of 1,022, two PLMs are respectively employed to extract features from the two different residue sequences, these extracted features are fused to represent the protein sequence. The dimensionality reduction algorithm is applied to the fused features and obtain the optimal feature subset. The optimal feature subset can fully capture complementary information across sequence lengths and across different PLMs. In the feature modeling stage, we construct a bi-directional long short-term memory (BiLSTM) network incorporating an attention mechanism to capture long-range dependencies and deep semantic dependencies within sequences. On the MHC identification task, DFL-MHC achieves better performance than the existing methods. It is demonstrated that the effectiveness of leveraging both multi-view feature fusion and dual-stage training to achieve accurate and reliable MHC identification.

In this study, we successfully isolated and cultured bovine skeletal muscle satellite cells (bSMSCs) and induced muscle cell formation in vitro. Skeletal muscle satellite cells (SMSCs) were isolated from the deep tissues of foetal bovine hind limbs and differentiated with 2% horse serum in vitro. The transcriptome sequencing results revealed a total of 1030 differentially expressed genes (DEGs) in the middle stage of differentiation (day 3) compared with the predifferentiation stage (day 0). A total of 374 DEGs were identified in the postdifferentiation stage (day 7) compared with the middle differentiation stage (day 3). We further investigated the regulatory effects of the DEG nerve growth factor (NGF) on the proliferation and myogenic differentiation of bSMSCs. The overexpression of NGF increased the mRNA and protein expression levels of myosin heavy chain (MyHC) and myogenin (MyoG), which are myoblast development markers, whereas NGF knockdown had the opposite effect; however, NGF did not affect the expression of the proliferation marker paired box gene 7 (Pax7) in bSMSCs. In addition, functional enrichment analysis of the DEGs revealed that the PI3K/Akt signalling pathway was significantly enriched in the DEGs and that NGF regulates myogenesis through the activation of the PI3K/Akt signalling pathway. Our results revealed that NGF was shown to be a putative regulator that controls myogenesis by activating the PI3K/Akt signalling pathway. The study provided a reference for further studies on the molecular mechanism of myogenic differentiation, regulatory network establishment, and beef quality improvement.

This review highlights recent advances and ongoing challenges in the genomics, genetics, and gene-editing (3G) of the freshwater snail Biomphalaria glabrata, based on insights gained from a novel model system we initiated two decades ago. B. glabrata is an intermediate host of the human blood fluke Schistosoma mansoni and serves as the principal model organism for schistosomiasis research. We developed two homozygous lines of B. glabrata, the iM line and iBS90, through 81 and 41 generations of selfing the commonly used M line and BS90, respectively. These lines display contrasting infection phenotypes: susceptibility or resistance to S. mansoni. High-quality scaffold-based genome assemblies were generated for both lines, followed by a chromosome-level assembly of the iM line genome. An F₂ segregating population derived from these lines enabled the identification of three loci, two linked to resistance or susceptibility and one associated with pigmentation, using a double digest restriction-site associated DNA sequencing (ddRADseq) approach. Recombinant inbred lines (RILs) were developed through two crosses and ten generations of selfing. Genetic mapping with RILs refined the resistance locus on chromosome 5 from 8 to 3 Mb through individual-based whole-genome sequencing. Ongoing work includes comparative transcriptome analyses of the two homozygous lines and RILs in response to schistosome infection, along with fine-scale mapping of advanced intercross lines to elucidate the molecular basis of the snail's anti-schistosome defenses. Over the past 10 years, we have made extensive efforts to achieve germline delivery and generate genetically modified snails. Although pantropic lentiviral and yolk protein-mediated germline delivery methods were unsuccessful, these pioneering experiments provide valuable insights for future research. Finally, we successfully generated germline-edited B. glabrata, the first genetically modified schistosomiasis vector snail, by microinjecting CRISPR/Cas9 and guide RNA (gRNA) targeting the fibrinogen-related protein 3.1 (FREP3.1) gene into decapsulated embryos, followed by ex ovo culture. This breakthrough establishes a foundation for innovative genetic strategies to control this neglected tropical disease.