Mol. Genet. Genomics [JOURNAL]
Sun
200 papers
New variant in KITLG shapes the pathogenesis of familial progressive hyper- and hypo-pigmentation.
Wu B, He M, Liu T … +9 more , Zhao W, Ye J, Jiang T, Teng C, Huang Y, Zhang Y, Li J, Shi H, Zhang J
Mol Genet Genomics · 2026 Mar · PMID 41779177 · Publisher ↗
Familial progressive hyper- and hypo-pigmentation (FPHH) is a pigmentary disorder characterized by a mixture of hypo- and hyper-pigmentation lesions, brown spots, and hypo-pigmentation gray leaf spots. This disease had p...
Familial progressive hyper- and hypo-pigmentation (FPHH) is a pigmentary disorder characterized by a mixture of hypo- and hyper-pigmentation lesions, brown spots, and hypo-pigmentation gray leaf spots. This disease had previously been reported to be associated with the KITLG gene. In this study, whole exome sequencing was performed to identify the gene mutation in two patients suspected with FPHH. Functional changes were explored at a cellular level with the help of adenine base editors, and the differentially expressed genes in the melanin pathway were detected through RNA-sequencing. Mutations were identified in two patients at exon 4 of KITLG (NM_000899.4): [c.329 A > T] and [c.329 A > G]. The c.329 A > G is a de novo mutation. The two variations were located in a conservative region and were predicted to be likely pathogenic mutations. For de novo c.329 A > G mutation, results showed that the mutation broadly affected the transcription and translation of genes responsible for melanin synthesis, especially the melanin gene MITF. These results indicated that the conservative locus c.329 A had an important function to KITLG, mutations [c.329 A > T] and [c.329 A > G] in KITLG could result FPHH. Based on the functional tests, c.329 A > G could be pathogenic mutant. This study has an important clinical significance, and it would extend the mutation spectrum of KITLG gene. It would improve the disease knowledge base and offer a reliable reference for the clinical diagnosis and prevention of FPHH.
The evolution of the Vibrio genome: the discovery of the pan-genome and the functional specialization of chromosomes.
Volodarskiy M, Rayko M
Mol Genet Genomics · 2026 Mar · PMID 41779090 · Publisher ↗
The genus Vibrio comprises a taxonomically and functionally diverse group of bacteria, including numerous species of relevance to human health, marine ecosystems, and aquaculture. In this study, we performed a comparativ...
The genus Vibrio comprises a taxonomically and functionally diverse group of bacteria, including numerous species of relevance to human health, marine ecosystems, and aquaculture. In this study, we performed a comparative pan-genome and core-genome analysis of 76 reference Vibrio genomes to investigate genomic diversity, chromosome-specific functional organization, and virulence-associated gene content across the genus. The pan-genome of the genus has an open structure, while the size of the core-genome remains stable and is significantly smaller than the proportion of added genes. The total number of genes per species varies from 2,765 to 5,693. Functional annotations by COG categories revealed differences in profiles between chromosomes. Additionally, a search for virulence factors was performed using the VFDB database, with the highest number found in the pathogenic species V. cholerae and V. parahaemolyticus. Taken together, our results demonstrate extensive genomic diversity within the genus Vibrio and indicate chromosome-specific functional specialization, with accessory genome components-particularly on the second chromosome-being closely associated with pathogenic potential. These findings contribute to a deeper understanding of genome organization, ecological adaptation, and virulence evolution in vibrios and provide a basis for future comparative and functional genomic studies relevant to public health and aquaculture.
A colorectal cancer risk model based on cell adhesion-related genes for predicting prognosis and immunological features.
Guo Z, Zhang W
Mol Genet Genomics · 2026 Mar · PMID 41779075 · Publisher ↗
Colorectal cancer (CRC) remains among the leading causes of cancer mortality worldwide, with tumor heterogeneity and immunosuppressive microenvironments posing major challenges to effective risk stratification and immuno...
Colorectal cancer (CRC) remains among the leading causes of cancer mortality worldwide, with tumor heterogeneity and immunosuppressive microenvironments posing major challenges to effective risk stratification and immunotherapy. Although cell adhesion molecules (CAMs) are well-established drivers of CRC progression through metastasis and immune evasion, their potential as integrated prognostic biomarkers and therapeutic targets remains underexplored. This study systematically characterizes CAM-related gene signatures to develop a robust prognostic framework that refines CRC risk assessment, elucidates immune regulatory mechanisms, and identifies precision therapy opportunities. Using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) transcriptomic datasets, we identified adhesion-related genes (ARGs) and constructed an 8-gene prognostic model via Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression. We evaluated immune infiltration, mutation burden, drug sensitivity, mendelian randomization (MR) causality, and defined novel molecular subtypes through consensus clustering. The 8-gene risk model effectively stratified patients into high- and low-risk groups with markedly different survival outcomes. High-risk patients exhibited immunosuppressive tumor microenvironments, reduced immunotherapy response, and distinct therapeutic vulnerabilities. MR confirmed a causal role for SLAMF1 in CRC risk. This ARG-driven prognostic framework not only enhances precision risk stratification in CRC but also reveals subtype-specific immune evasion mechanisms and therapeutic targets. These findings offer actionable insights for personalized CRC management and underscore CAMs as promising candidates for future functional and translational studies across gastrointestinal malignancies.
Single-cell transcriptomic profiling combined with Mendelian randomization illuminates molecular drivers of bladder cancer.
He J, Jiang Z, Peng S … +6 more , Peng L, Xia Z, Ma T, Tan X, Long Q, Wu J
Mol Genet Genomics · 2026 Mar · PMID 41779063 · Full text
Bladder cancer exhibits marked cellular heterogeneity, which complicates the identification of molecular drivers with both functional and genetic relevance. The link between genetic susceptibility and transcriptional act...
Bladder cancer exhibits marked cellular heterogeneity, which complicates the identification of molecular drivers with both functional and genetic relevance. The link between genetic susceptibility and transcriptional activity in tumorigenesis remains incompletely understood. Single-cell transcriptomes of bladder carcinoma and adjacent normal tissues were processed using Seurat and Harmony for data normalization, integration, and dimensionality reduction. Differentially expressed genes were further prioritized using causal inference based on genome-wide association and expression quantitative trait loci data. Functional analyses included pathway enrichment, immune profiling, and transcription factor network inference. Candidate genes were validated through immunohistochemistry, quantitative PCR, and Western blotting, and in vitro cell-based assays (including CCK-8, scratch wound healing, transwell invasion, and flow cytometry analysis). Among all cellular populations, B cells showed the highest fold-change score. Mendelian randomization highlighted six bladder-cancer-related genes-ARHGEF18, HLA-DRB5, ISG20, NCF1, RPL13, and YPEL5. ARHGEF18 raised risk (OR 1.001; 95% CI 1.000-1.002; P 0.017), whereas YPEL5 showed a protective association (OR 0.997; 95% CI 0.995-0.999; P 0.003). Immunohistochemistry confirmed elevated ARHGEF18 and reduced YPEL5 expression in tumor tissues. In vitro experiments demonstrated that ARHGEF18 knockdown and YPEL5 overexpression led to decreased cell proliferation, migration, invasion, and increased apoptosis in T24 and 5637 bladder cancer cells. Our findings identify ARHGEF18 and YPEL5 as genetically and transcriptionally supported regulators of bladder cancer, highlighting a scalable strategy for linking genetic risk to cell-type-specific mechanisms.
Identification and functional analysis of exonic SNPs in MMP2 and MMP3 genes as prognostic biomarkers for breast cancer patients.
Chan SC, Chin FW, Noor Akmal S … +2 more , Abdul Rahman S, Rosli R
Mol Genet Genomics · 2026 Mar · PMID 41779051 · Publisher ↗
Breast cancer is the most prevalent malignancy among women worldwide, and metastasis remains the leading cause of breast cancer-related deaths. Matrix metallopeptidase genes MMP2 and MMP3 are key regulators of extracellu...
Breast cancer is the most prevalent malignancy among women worldwide, and metastasis remains the leading cause of breast cancer-related deaths. Matrix metallopeptidase genes MMP2 and MMP3 are key regulators of extracellular matrix degradation and tumour invasion, yet the role of their exonic single nucleotide polymorphisms (SNPs) in breast cancer progression remains unexplored. This study aimed to identify exonic SNPs in MMP2 and MMP3 among Malaysian breast cancer patients, to assess their functional effects on mRNA structure and stability, and to evaluate their prognostic value in breast cancer metastasis. In total, 36 SNPs (21 in MMP2 and 15 in MMP3), including 10 novel SNPs and one novel deletion, were identified using high-resolution melting (HRM) analysis and confirmatory DNA sequencing. Logistic regression analysis revealed that two exonic SNPs, c.1842C>G (MMP2) and c.1070-23T>A (MMP3) were significant predictors of metastasis, improving the accuracy and sensitivity of the predictive model compared with clinicopathological factors alone. Bioinformatics analysis further showed that c.1842C>G and several other exonic SNPs altered mRNA secondary structure, potentially reducing metastasis risk by diminishing mRNA stability. In addition, synonymous SNPs (sSNPs) such as c.678G>C (MMP2), c.288T>C (MMP3), and c.626-14A>G (MMP3) exhibited overdominance effects, with heterozygous genotypes modulating mRNA folding and stability and thereby exerting a protective influence against metastasis. These findings highlight exonic SNPs in MMP2 and MMP3 as promising prognostic biomarkers for breast cancer, with the potential to improve metastasis risk assessment and support more personalised approaches to patient management. Validation in larger, ethnically diverse cohorts will be important to confirm their clinical utility and to elucidate the underlying biological mechanisms.
LncRNA CARD8-AS1 acts as a potential novel biomarker and promotes atrial fibrillation progression via the miR-31-5p/ARRB1 pathway.
Du Y, Zhao B, Lian J
Mol Genet Genomics · 2026 Mar · PMID 41779038 · Publisher ↗
BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia linked to atrial fibrosis, yet reliable biomarkers and mechanisms remain unclear. LncRNAs have emerged as crucial regulators of cardiac remodelling and arrhythm...
BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia linked to atrial fibrosis, yet reliable biomarkers and mechanisms remain unclear. LncRNAs have emerged as crucial regulators of cardiac remodelling and arrhythmogenesis, but the role of LncRNA CARD8-AS1 in AF has not been elucidated. This study aimed to investigate the expression, clinical diagnostic value, and molecular mechanism of CARD8-AS1 in AF. METHODS: Clinical data and serum samples were collected from 130 AF patients (76 with left atrial fibrosis, LAF) and 75 sinus rhythm (SR) individuals. RT-qPCR detected CARD8-AS1, miR-31-5p, and ARRB1 expression. ROC curves assessed diagnostic efficacy. In human atrial fibroblasts (HAFs), Ang-II was used to simulate fibrosis. CCK-8, Transwell, and molecular assays evaluated cell function and pathway molecules. Bioinformatics and luciferase assays verified molecular interactions. RESULTS: CARD8-AS1 was upregulated in AF patients, especially those with LAF, and effectively differentiated AF from SR and AF with LAF. CARD8-AS1 expression was correlated with LAd, LVEF, and fibrotic markers. In HAFs, Ang-II increased CARD8-AS1, enhancing cell viability, migration, and fibrotic marker expression, while CARD8-AS1 knockdown reversed these. CARD8-AS1 directly targeted miR-31-5p, which targeted ARRB1. The CARD8-AS1/miR-31-5p/ARRB1 axis mediated Ang-II-induced HAF activation. CONCLUSIONS: CARD8-AS1 is a potential diagnostic biomarker for AF and promotes AF progression via the miR-31-5p/ARRB1 pathway. Future studies may focus on validating the clinical utility of CARD8-AS1 in larger cohorts and exploring its therapeutic potential via targeted inhibition strategies.
Advances in functional transcriptome analysis of Mycobacterium tuberculosis: a review.
Sundaram K, Rathinam S
Mol Genet Genomics · 2026 Mar · PMID 41774181 · Publisher ↗
Drug-resistant tuberculosis poses a significant global challenge necessitating the prompt advancement of novel therapeutic options. Nonetheless, disease prognosis is contingent upon multiple factors. mRNA and other small...
Drug-resistant tuberculosis poses a significant global challenge necessitating the prompt advancement of novel therapeutic options. Nonetheless, disease prognosis is contingent upon multiple factors. mRNA and other small RNAs are essential for gene regulation and disease progression. Additionally, they are essential for the advancement of TB mRNA therapies. The review aims to evaluate the functions of mRNA and various small RNAs, including lncRNA, miRNA, circRNA, and ceRNA, as interconnected components within the mRNA-miRNA-circRNA axis in Mycobacterium tuberculosis. In this context, the analysis of various genes expressed during transcription is essential; however, the TB group’s mRNA expression levels of the CXCL10, CXCL9, IL1B, and PLA2G2D genes were substantially higher compared to the control group. In addition, EspC, MetE, and PPE15 increased IgG levels. Besides, the inadequate IgG responses to m-ESAT6 and m-EsxI present a noteworthy research opportunity. Evidence that neutralizing antibodies provide protection against viral infections targeted by mRNA vaccines during the COVID-19 pandemic supports this research. mRNA-based vaccination analogues offer potential therapeutic advantages following BCG administration. Mycobacterium avium and Mycobacterium tuberculosis are efficiently inhibited by the mRNA therapy, namely the repRNA-ID91/ID91 + GLA-SE vaccination, which elicits humoral and cellular immune responses. Therefore, the therapeutic use of mRNA, as demonstrated by numerous studies, suggests its potential as an efficacious therapeutic vaccine subsequent to BCG treatment. Also, investigating the ceRNA network and the relationships among miRNA, circRNA, lncRNA, and mRNA in TB study will improve the management of this infection.
Genetic architecture of drought resilience in barley (Hordeum vulgare L.) revealed by genome-wide association study.
Alwutayd KM, Shami A, Alqudah AM … +1 more , Thabet SG
Mol Genet Genomics · 2026 Mar · PMID 41772117 · Publisher ↗
Drought stress is a major constraint to barley (Hordeum vulgare L.) production worldwide, with recurrent and variable drought episodes challenging yield stability. Understanding the genetic basis of drought adaptation ac...
Drought stress is a major constraint to barley (Hordeum vulgare L.) production worldwide, with recurrent and variable drought episodes challenging yield stability. Understanding the genetic basis of drought adaptation across different drought history treatments is essential for breeding resilient cultivars. A genome-wide association study (GWAS) was conducted using high-density SNP genotyping across multiple drought history scenarios, including control and combinations of early- and late-generation drought exposure. Drought priming across generations enhanced yield and biochemical traits, with the strongest biochemical gains in the second generation, while continuous drought produced the most consistent improvements in both yield stability and defense responses. GWAS identified multiple highly significant and stable loci across the barley genome, with recurrent association hotspots on chromosomes 4H, 5H, 6H, and 7H. Notable SNPs such as chr4H:439308083:G:A, chr5H:621040118:C:T, and chr7H:493258982:C:T influenced multiple traits across treatments, suggesting pleiotropic effects. Candidate genes included members of the protein kinase family, aldehyde dehydrogenases, and other stress-responsive regulators involved in signal perception, ABA signaling, osmotic adjustment, and oxidative stress detoxification. Protein kinases, particularly MAPKs, SnRKs, and CDPKs, likely mediate rapid and efficient drought signal transduction, while aldehyde dehydrogenases contribute to sustained protection against reactive aldehydes generated during water deficit. The recurrence of specific SNPs across environmental contexts highlights their robustness as potential breeding targets. This study provides novel insights into the genomic architecture of drought tolerance in barley under variable drought histories, identifying key loci and candidate genes with functional relevance to stress adaptation.
Glycan and glycoprotein signatures in tumor-induced liver alterations in a murine breast cancer model.
Turker NP, Bakar E
Mol Genet Genomics · 2026 Mar · PMID 41770230 · Publisher ↗
Liver-associated alterations are increasingly recognized as critical contributors to breast cancer progression and systemic disease burden, yet the molecular mechanisms underlying these changes remain poorly understood....
Liver-associated alterations are increasingly recognized as critical contributors to breast cancer progression and systemic disease burden, yet the molecular mechanisms underlying these changes remain poorly understood. In particular, aberrant protein glycosylation has emerged as a key regulator of cancer-associated tissue remodeling and inter-organ communication. In this study, we investigated whether glycosylation-related gene expression and glycoprotein signatures in liver tissue could serve as biomarkers of breast cancer-associated hepatic alterations. We developed a medium-throughput quantitative real-time reverse transcriptase-PCR array targeting genes encoding glycosyltransferases and glycosylhydrolases involved in glycan synthesis, modification, and catabolism. This approach enabled a systematic analysis of over 134 glycosylation-related genes and facilitated direct integration of transcriptomic data with glycan structural profiles in the liver tissue of breast tumor-bearing mice. Our analysis revealed significant upregulation of Galntl2, GNE, and Manea, accompanied by increased sialic acid levels in both liver and circulating blood. Receiver operating characteristic (ROC) analysis demonstrated that these genes exhibit excellent diagnostic performance in liver tissue, achieving 100% sensitivity and specificity. Collectively, these findings highlight glycosylation-related gene signatures as robust indicators of breast cancer-associated liver alterations and suggest that dysregulated hepatic glycosylation represents a biologically meaningful axis linking tumor progression with systemic metabolic and glycomic remodeling. This work provides a framework for exploring glycosylation-based biomarkers and therapeutic targets in cancer-associated organ dysfunction.
Immunoinformatics-guided design of a multi-epitope vaccine targeting the envelopment polyprotein of oropouche virus.
Naveed M, Athar A, Tariq A … +7 more , Asim M, Majeed MN, El Hadi Mohamed RA, Elkhadragy MF, Alwethaynani MS, Almsaud MM, Nabi G
Mol Genet Genomics · 2026 Feb · PMID 41706189 · Publisher ↗
Oropouche virus is an emerging and neglected arbovirus of growing public health concern in Latin America, with recent epidemiological surveillance reporting 832 confirmed cases in 2023 and 5,913 cases during early 2024 i...
Oropouche virus is an emerging and neglected arbovirus of growing public health concern in Latin America, with recent epidemiological surveillance reporting 832 confirmed cases in 2023 and 5,913 cases during early 2024 in Brazil, predominantly in the Amazon region. Despite its increasing spread, no licensed vaccines or antiviral therapies are currently available. In this study, we aimed to design and computationally evaluate a multi-epitope vaccine candidate targeting the OROV envelopment polyprotein using integrated immunoinformatics, molecular modeling, and immune simulation approaches. The complete polyprotein sequence was analyzed to identify antigenic, non-allergenic, and non-toxic cytotoxic and helper T-cell epitopes. Selected epitopes were assembled into a chimeric construct incorporating an adjuvant, suitable linkers, and a PADRE sequence to enhance immune recognition. Physicochemical properties, tertiary structure, receptor binding, dynamic stability, and immune response potential were comprehensively evaluated in silico. The final vaccine construct comprised 241 amino acids and demonstrated favorable stability with instability index score of 24.95, hydrophilicity with GRAVY score of - 0.241, and with an estimated global population coverage of 94.07%. Molecular docking revealed favourable binding affinity to TLR4 with a binding energy of - 1067.1, while molecular dynamics simulations showed structural stability, with an average RMSD of 0.40 nm and limited fluctuations. Immune simulations predicted rapid antigen clearance, robust Th1-polarized responses characterized by strong IFN-γ and IL-2 production, sustained IgG responses, and expansion of memory B and T cells. Overall, these findings indicate that the proposed multi-epitope vaccine construct is stable, immunogenic, and capable of inducing broad immune responses, providing a strong rationale for experimental validation and future vaccine development against Oropouche virus.
Bioinformatics-guided vaccine targeting the hemagglutinin protein of avian influenza virus.
Khursheed S, Ahmed MZ, Khursheed S … +2 more , Mutahir Z, Samad N
Mol Genet Genomics · 2026 Feb · PMID 41686297 · Publisher ↗
Avian influenza viruses (AIV) represent a major zoonotic threat to global public health and agriculture due to their high mutation rates, antigenic drift, and potential for interspecies transmission. This study addresses...
Avian influenza viruses (AIV) represent a major zoonotic threat to global public health and agriculture due to their high mutation rates, antigenic drift, and potential for interspecies transmission. This study addresses the urgent need for innovative, broad-spectrum vaccines that can overcome the limitations of traditional approaches, such as slow production and strain-specific protection, by designing and evaluating a novel multi-epitope protein-based vaccine targeting conserved regions of the AIV hemagglutinin (HA) protein through advanced immunoinformatics tools. Using an in silico approach, conserved 4 MHC-I, 9 MHC-II, and 5 B-cell epitopes were identified, screened for antigenicity, non-toxicity, and non-allergenicity, and integrated into a rationally designed vaccine construct optimized with a tPA signal peptide, the RpfE adjuvant, and immunostimulatory elements. The AIV vaccine construct exhibited favorable physicochemical properties, including a molecular weight of 64.8 kDa, a basic pI, antigenicity (0.5871), non-toxicity, non-allergenicity, and high solubility (0.747). The tertiary structure, predicted using RoseTTAFold, refined with GalaxyRefine, and then validated by a Ramachandran plot (97.4% residues in favored regions), demonstrated high stereochemical reliability. Linear and conformational B-cell epitopes were mapped, indicating strong antibody elicitation potential. Molecular docking, normal mode analysis, and molecular dynamics simulation confirmed a stable interaction with human TLR3, characterized by a favorable binding energy (ΔGbind = − 16.96 ± 4 kcal/mol) and stable complex dynamics. Immunogenicity simulations revealed elevated levels of IgG and IgM, accompanied by increased immune cell responses. The gene was cloned into the PET28a(+) vector, producing a 5.2 kb plasmid suitable for expression. In conclusion, this in silico-designed vaccine candidate demonstrates promising potential as a broad-spectrum immunogen against AIV, leveraging computational vaccinology to mitigate antigenic drift and zoonotic risks; future perspectives include experimental validation via in vitro and in vivo studies to confirm safety, immunogenicity, and efficacy, enabling rapid deployment against emerging influenza threats.
Bioinformatics characterization and tissue-specific expression of MARCKS and MLP genes in the regenerating salamander Cynops orientalis.
Shui L, Feng YL, Liu WH
Mol Genet Genomics · 2026 Feb · PMID 41686276 · Publisher ↗
Myristoylated alanine-rich C-kinase substrate (MARCKS) and MARCKS-like protein (MLP) play a key role in initial axolotl limb regeneration. However, the basic bioinformatics characteristics and expression profiles of the...
Myristoylated alanine-rich C-kinase substrate (MARCKS) and MARCKS-like protein (MLP) play a key role in initial axolotl limb regeneration. However, the basic bioinformatics characteristics and expression profiles of the two genes in newts remain unclear. To investigate the important biological characteristics of newt MARCKS and MLP, the open reading frame (ORF) sequences of MARCKS and MLP were obtained from Cynops orientalis (C. orientalis) and subjected to comprehensive bioinformatics and tissue expression analyses for the two genes. The results showed that the complete ORF sequences of Co-MARCKS and Co-MLP were 837 bp (encoding 278 amino acids) and 684 bp (encoding 227 amino acids) respectively. Both Co-MARCKS and Co-MLP were dominated by random coils, and neither protein contained a signal peptide. Both Co-MARCKS and Co-MLP contain three highly conserved domains, including the N-terminal myristoylation motif, the MARCKS homology domain 2, and the effector domain. Furthermore, Co-MARCKS and Co-MLP were predicted to contain eight and five potential phosphorylation sites respectively. Notably, the phosphorylation sites at Ser of Co-MARCKS and at Ser of Co-MLP were located in their respective effector domains, implying critical roles in protein function. Phylogenetic analysis revealed that Co-MARCKS and Co-MLP shared the closest evolutionary relationship with those of Pleurodeles waltl. Expressions of the two genes were detected in the liver, spleen, stomach and intestine of C. orientalis. Importantly, the expression levels of Co-MLP in the liver and stomach were each significantly higher than those in the spleen and intestine (P < 0.05). In conclusion, this study indicated that the dynamic structures and phosphorylation of newt MARCKS and MLP play a crucial role in their function, providing a molecular foundation for future functional studies of these genes in newt limb regeneration.
Genome-wide association study reveals acute mountain sickness susceptibility in Chinese population.
Zheng X, Song W, Li Y … +16 more , Bao N, Li W, Liu Y, Liu J, Li B, Yang X, Han X, Wu J, Ma L, Liu Y, Jin M, Wang G, Yin D, Zhou W, Ye Q, Wang R
Mol Genet Genomics · 2026 Feb · PMID 41686271 · Publisher ↗
Acute mountain sickness (AMS) is a major health challenge in high-altitude environments, yet its genetic underpinnings, particularly in the Chinese population, remain poorly characterized. We conducted a genome-wide asso...
Acute mountain sickness (AMS) is a major health challenge in high-altitude environments, yet its genetic underpinnings, particularly in the Chinese population, remain poorly characterized. We conducted a genome-wide association study (GWAS) on 156 AMS patients and 313 controls in Chinese population, revealing four novel suggestive single nucleotide polymorphisms (SNPs) (P < 1 × 10). Among these four SNPs, two SNPs (rs1424442 and rs2246690) were successfully replicated in an independent cohort (P < 0.05), which contains 214 AMS patients and 196 controls. We provide functional insights for these two SNPs: the rs1424442-C allele is implicated in AMS susceptibility potentially by upregulating BPGM expression, thereby altering oxygen release and increasing red blood cell count (RBC) along with hemoglobin (HGB) concentration; while the rs2246690-A allele is associated with reduced UHRF2 expression in the prefrontal cortex and cognitive delay, offering a direct genetic link to AMS-related neurological impairment. Integrative analyses further substantiated the involvement of immune and gastrointestinal systems in AMS pathogenesis. Our work not only reports new genetic associations but also proposes specific molecular mechanisms, providing a valuable foundation for understanding AMS and developing future interventions.
Multi-model GWAS reveals genetic determinants of grain hardness, size and weight in bread wheat (Triticum aestivum L.).
Bhadana D, Kumar J, Ahmed S … +4 more , Kumari A, Garg M, Roy J, Kumar R
Mol Genet Genomics · 2026 Feb · PMID 41653313 · Publisher ↗
Grain quality traits such as kernel hardness index (KHI), kernel diameter (KD), and thousand grain weight (TGW) are pivotal determinants of processing quality and yield potential in bread wheat (Triticum aestivum L.). In...
Grain quality traits such as kernel hardness index (KHI), kernel diameter (KD), and thousand grain weight (TGW) are pivotal determinants of processing quality and yield potential in bread wheat (Triticum aestivum L.). In this study, we performed a comprehensive genome-wide association study (GWAS) using eight advanced multi-locus models implemented in GAPIT v3.0 to dissect the genetic architecture underlying these traits across 225 spring wheat genotypes evaluated under two distinct environments. A total of 739 significant quantitative trait nucleotides (QTNs) were identified across all datasets using eight different models, with the most QTNs detected by the BLINK and FarmCPU models. Thirty-six common QTNs were detected by all models across traits, including stable QTNs for KHI, KD, and TGW, with several showing pleiotropic effects. Notably, 13 QTNs for KHI were consistently detected across environments, underscoring their potential for marker-assisted selection (MAS). Comparative analysis revealed that 8 QTNs overlapped with previously reported QTLs, particularly for KHI and TGW, thereby validating their reliability. In contrast, no overlaps were observed for KD, suggesting novel loci for this trait. Five highly promising QTNs were prioritized based on stability, multi-trait associations, and detection consistency. Candidate gene analysis revealed 1,916 genes associated with KHI, KD, and TGW, with functional annotation indicating enrichment of domains related to lipid metabolism (GDSL esterases), signalling (protein kinases), assimilate transport (CRAL-TRIO and sucrose transporters), and cell-wall modification (expansins). Differential in-silico expression across grain-related tissues supported their functional relevance. Analysis of 36 common MTAs refined a subset of 95 candidate genes representing key regulatory pathways underlying grain quality traits. The stable QTNs and biologically relevant candidate genes identified in this study provide valuable resources for fine-mapping, MAS, and functional validation, which may support the development of high-yielding wheat cultivars with improved grain quality.
Stroke risk nomograms from machine learning need clearer calibration and transportability assessment.
De Rango F, Pastore EP
Mol Genet Genomics · 2026 Feb · PMID 41653290 · Publisher ↗
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Circ-FoxO3 alleviates APOE4-induced brain pathology through FoxO3-mediated autophagy.
He K, Wei H, Chen Q … +5 more , Wen X, Ding W, Li Y, Li K, Yang Z
Mol Genet Genomics · 2026 Feb · PMID 41653210 · Publisher ↗
The APOE4 is a well-established and significant genetic risk factor associated with the accumulation of β-amyloid (Aβ) plaques and hyperphosphorylated tau (p-tau) in the pathogenesis of Alzheimer's disease (AD). Our prev...
The APOE4 is a well-established and significant genetic risk factor associated with the accumulation of β-amyloid (Aβ) plaques and hyperphosphorylated tau (p-tau) in the pathogenesis of Alzheimer's disease (AD). Our previous research has implicated circular RNA FoxO3 (circ-FoxO3) in the clearance of aggregated proteins in ischemic stroke. However, the role of circ-FoxO3 in the accumulation of abnormal proteins during AD development remains unclear. In this study, we demonstrate that circ-FoxO3 mitigates APOE4-driven neurotoxic protein aggregation by enhancing FoxO3-mediated autophagy. Specifically, transgenic mice expressing human APOE4 exhibited elevated levels of p-tau and Aβ, and these pathological alterations were significantly ameliorated by circ-FoxO3. Mechanistically, we found that circ-FoxO3 upregulates its host gene FoxO3, leading to activation of autophagy and subsequent clearance of neurotoxic protein aggregates. The findings highlight a critical role for circ-FoxO3 in counteracting APOE4-induced brain damage and suggest its potential as a therapeutic target for mitigating APOE4-related neuropathology.
Genome-wide analysis of the R2R3-MYB family reveals potential regulators of lignin and tricin metabolism in the model grass Setaria viridis.
Cerruti GV, da Cunha LX, Cursino AC … +2 more , Simões MS, Cesarino I
Mol Genet Genomics · 2026 Feb · PMID 41653195 · Full text
R2R3-MYBs constitute one of the largest families of plant transcription factors and several members are involved in the regulation of distinct branches of the phenylpropanoid pathway, acting as activators or repressors o...
R2R3-MYBs constitute one of the largest families of plant transcription factors and several members are involved in the regulation of distinct branches of the phenylpropanoid pathway, acting as activators or repressors of the biosynthesis of a plethora of specialized metabolites. Although R2R3-MYBs have been extensively characterized as regulators of lignin deposition in distinct cellular contexts and species, still little is known about their roles in regulating specific aspects of grass lignification. Here, we report on the genome-wide characterization of the R2R3-MYB family in the model grass Setaria viridis and identification of members potentially involved in the regulation of lignin/tricin metabolism. A total of 132 genes encoding R2R3-MYBs were found in S. viridis, which clustered in 43 well-supported subgroups. Comprehensive in silico expression, co-expression, and RT-qPCR analyses allowed the identification of 4 candidate SvMYBs that showed (i) similar expression profiles to that observed for lignin biosynthetic genes in a set of different organs/conditions of S. viridis; (ii) similar expression patterns to that of lignin biosynthetic genes along the S. viridis elongating internode; (iii) co-expression with several phenylpropanoid- and lignin-related genes in public transcriptomic databases; (iv) high expression levels in the top of the S. viridis elongating internode, a tissue undergoing active lignification. Three of these SvMYBs activated the promoters of lignin and tricin biosynthetic genes in transactivation assays using tobacco protoplasts. Altogether, our results suggest that these three transcription factors control grass-specific aspects of lignin deposition and further studies might confirm their ability to control lignin deposition and tricin metabolism in S. viridis.
Circular RNAs: key regulators in cancer stem cell dynamics.
Jain P, Kaushik V, Chhabra R
Mol Genet Genomics · 2026 Feb · PMID 41632314 · Publisher ↗
Circular RNAs (circRNAs) are non-coding RNAs with single stranded structure devoid of a 5’ cap and poly-A tail. Although the first circRNA was discovered in the 1970s, the abundance and significance of circRNAs was only...
Circular RNAs (circRNAs) are non-coding RNAs with single stranded structure devoid of a 5’ cap and poly-A tail. Although the first circRNA was discovered in the 1970s, the abundance and significance of circRNAs was only realized with the advent of high-throughput RNA-sequencing technologies and bioinformatics analysis. The recent studies have highlighted the variable expression of circRNAs in patient tumor samples. Cancer stem cells (CSCs) are thought to be responsible for initiation and progression of tumors. The cancer stem cell hypothesis states that a small subpopulation of cells within the tumor possesses the ability to self-renew and differentiate into non-stem cells of the tumor. CSCs have the characteristic features of chemo- and radio-resistance, the ability to metastasize, and are often linked with cancer relapse. The clinical data indicates a negative correlation between the proportion of CSCs in tumors and the overall survival of cancer patients. The higher the number of CSCs in a tumor sample, the more aggressive is the tumor. Targeting CSCs is, therefore, a potent therapeutic approach in cancer treatment. This review provides a comprehensive overview of circRNAs and critically evaluates their role in the regulation of CSCs.
Methylome and transcriptome analysis reveal the impact of psychological stress on the skin.
Li B, Zou Y, Tian S … +6 more , Gonda L, Mahns A, Huang T, Kolbe L, Shi Y, Wang S
Mol Genet Genomics · 2026 Feb · PMID 41632209 · Publisher ↗
Psychological stress is increasingly recognized as an important determinant of human skin health, but the molecular and epigenetic mechanisms by which it affects the epidermis are still not well understood. To investigat...
Psychological stress is increasingly recognized as an important determinant of human skin health, but the molecular and epigenetic mechanisms by which it affects the epidermis are still not well understood. To investigate whether psychological stress is associated with molecular differences in the epidermis, and how these might relate to skin phenotypes, we performed a multi-omics study in 60 stressed and 60 relaxed young adults. From lower-back epidermal samples, we generated DNA methylation profiles and RNA-seq data, and additionally measured skin cytokines and skin phenotypes. We identified 289 differentially methylated probes and 10 differentially expressed genes associated with psychological stress. Integration of methylation and expression with a functional epigenetic module approach yielded seven network modules; enrichment analyses of DMP-annotated genes and module genes revealed significant enrichment of terms related to glutamatergic synapse and synaptic signaling, in line with the emerging concept of a cutaneous neuroendocrine system. None of the 36 tested skin cytokines differed significantly between groups after correction for multiple testing. Skin darkening scores were higher in the stressed group. A CpG site in the SERPINA1 promoter and SERPINA1 expression were associated with this phenotype, and mediation analysis suggested that SERPINA1 expression partly mediated the association between cg01431455 methylation and skin darkening. Taken together, our study links psychological stress to coordinated differences in epidermal DNA methylation and gene expression, highlights glutamatergic and SERPINA1-related pathways as candidates for further mechanistic study, and establishes an epidermal multi-omics dataset for future work on stress-skin interactions.
Investigating the evolutionary history of the biosynthetic gene cluster for the cytotoxic purine analog, 6-thioguanine.
Bateman A, Most K, Stavrinides J
Mol Genet Genomics · 2026 Jan · PMID 41619050 · Publisher ↗
The aim of this study was to explore the distribution and evolution of the biosynthetic gene cluster that directs the synthesis of 6-thioguanine, a purine antimetabolite that has applications as a chemotherapeutic, and h...
The aim of this study was to explore the distribution and evolution of the biosynthetic gene cluster that directs the synthesis of 6-thioguanine, a purine antimetabolite that has applications as a chemotherapeutic, and has been studied for anti-inflammatory, antibacterial, and antiviral properties. Some bacteria, like members of the genus Erwinia, carry the ycfRABCD operon that directs the synthesis of 6-thioguanine. To explore its evolution, we surveyed for the presence of the cluster across all bacteria available in the public databases, and identified two distinct configurations of the gene cluster. One configuration is found exclusively within the Erwiniaceae and the Yersiniaceae (Gammaproteobacteria), and the second, which carries an additional gene, is found within members of the Alpha- and Betaproteobacteria. We found that the genomic location of ycf operon is conserved across divergent bacteria, with phylogenetic and %GC analyses suggesting that the cluster is evolutionarily old and vertically inherited. In some lineages, the cluster has been lost, while in others it has been acquired horizontally from distantly related groups. Maintenance of the cluster across diverse bacterial species suggests multiple roles for 6-thioguanine in the general ecology of these species.
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