Frontiers in Genetics最新文献

{"title":"<i>VCAM-1</i> predicts poor prognosis and modulates immune infiltration in gastric cancer: a TCGA-based bioinformatics study.","authors":"Cheng Wu, Yungeng Liu, Chuanyuan Liu, Chuanfa Fang","doi":"10.3389/fgene.2025.1602929","DOIUrl":"10.3389/fgene.2025.1602929","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a leading cause of cancer-related mortality; however, biomarkers predicting its immunotherapy resistance remain scarce. Vascular cell adhesion molecule (<i>VCAM</i>)-<i>1</i>, an immune cell adhesion mediator, is implicated in tumor progression; however, its prognostic and immunomodulatory roles in GC remain unclear.</p><p><strong>Methods: </strong>In this study, we analyzed <i>VCAM-1</i> expression and its clinical relevance in GC using RNA-sequencing data from The Cancer Genome Atlas. Differential gene analysis, gene set enrichment analysis (GSEA), and single-sample GSEA were used to identify the underlying pathways and immune infiltration patterns. Validation was performed via Cox regression, receiver operating characteristic, and immunohistochemical (Human Protein Atlas database) analyses.</p><p><strong>Results: </strong><i>VCAM-1</i> expression levels were significantly upregulated in the GC tissues (p < 0.001) and correlated with advanced T stage (p = 0.046), N stage (p = 0.047), and poor overall survival (hazard ratio = 1.54; p = 0.046). GSEA linked <i>VCAM-1</i> expression to various immune pathways (e.g., interleukin-17 signaling), and single-sample GSEA revealed its positive associations with the Th1, cytotoxic, and CD8⁺ T cell proportions (p < 0.05) and inverse correlation with the Th17 cell proportion. Immunohistochemistry revealed elevated VCAM-1 protein levels in the tumors.</p><p><strong>Conclusion: </strong><i>VCAM-1</i> is a novel prognostic biomarker driving immunosuppressive microenvironmental remodeling in GC. Furthermore, its dual roles in immune regulation highlight its potential to optimize GC immunotherapy.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1602929"},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drought adaptation index (DAI) based on BLUP as a selection approach for drought-resilient switchgrass germplasm.","authors":"Shiva Om Makaju, Hari Bahadur Chhetri, Chanaka Roshan Abeyratne, Mirko Pavicic, Hari Poudel, Jazib Ali Irfan, Anita Giabardo, Katrien M Devos, Daniel Jacobson, Ali Mekki Missaoui","doi":"10.3389/fgene.2025.1626083","DOIUrl":"10.3389/fgene.2025.1626083","url":null,"abstract":"<p><p>This study introduces a Drought Adaptation Index (DAI), derived from Best Linear Unbiased Prediction (BLUP), as a method to assess drought resilience in switchgrass (<i>Panicum virgatum</i> L.). A panel of 404 genotypes was evaluated under drought-stressed (CV) and well-watered (UC) conditions over four consecutive years (2019-2022). BLUP-estimated biomass yields were used to calculate the DAI, which enabled classification of genotypes into four adaptation groups: very well-adapted, well-adapted, adapted, and unadapted. The DAI was compared with conventional drought tolerance indices, including the Stress Susceptibility Index (SSI), Stress Tolerance Index (STI), Geometric Mean Productivity (GMP), and Yield Stability Index (YSI). Correlation analyses demonstrated strong agreement between DAI and these indices, supporting its validity and consistency. Biplot analyses using the Genotype plus Genotype-by-Environment Interaction (GGE) and Additive Main Effects and Multiplicative Interaction (AMMI) models revealed significant genotype-by-environment interactions (GEI) and identified J222.A, J463.A, and J295.A. A as high-performing genotypes, with J222.A exhibiting greater yield stability across treatments and years. Additionally, DAI isoline curves provided a graphical representation of differential genotype performance under drought and control conditions. These visualizations aided in distinguishing genotypes with stable and superior biomass yield across contrasting environments. Overall, the BLUP-based DAI is a robust and practical selection tool that improves the accuracy of identifying drought-resilient, high-yielding switchgrass genotypes. Its integration into breeding programs offers a comprehensive framework for improving biomass productivity and stress adaptation under variable climatic conditions. The application of DAI supports the development of climate-resilient cultivars and contributes to sustainable bioenergy and forage production systems.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1626083"},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DeepRNAac4C: a hybrid deep learning framework for RNA N4-acetylcytidine site prediction.","authors":"Guohua Huang, Runjuan Xiao, Chunying Peng, Jinyun Jiang, Weihong Chen","doi":"10.3389/fgene.2025.1622899","DOIUrl":"10.3389/fgene.2025.1622899","url":null,"abstract":"<p><p>RNA N4-acetylcytidine (ac4C) is a crucial chemical modification involved in various biological processes, influencing RNA properties and functions. Accurate prediction of RNA ac4C sites is essential for understanding the roles of RNA molecules in gene expression and cellular regulation. While existing methods have made progress in ac4C site prediction, they still struggle with limited accuracy and generalization. To address these challenges, we propose <i>DeepRNAac4C</i>, a deep learning framework for RNA ac4C sites prediction. <i>DeepRNAac4C</i> integrates residual neural networks, convolutional neural networks (CNN), bidirectional long short-term memory networks (BiLSTM), and bidirectional gated recurrent units (BiGRU) to effectively capture both local and global sequence features. We extensively evaluated <i>DeepRNAac4C</i> against state-of-the-art methods using 10-fold cross-validation and independent tests. The results show that <i>DeepRNAac4C</i> outperforms existing approaches, achieving an accuracy of 0.8410. The proposed <i>DeepRNAac4C</i> improves predictive accuracy and model robustness, providing an effective tool for identifying RNA ac4C sites and deepening our understanding of RNA modifications and their functional roles in biological systems.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1622899"},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethanol-induced changes in neurotrophic and immune genes are regulated by receptor-type protein tyrosine phosphatase β/ζ (RPTPβ/ζ) and microglial-neuronal interactions.","authors":"María Aránzazu Penedo, Héctor Cañeque-Rufo, Esther Gramage, Gonzalo Herradón","doi":"10.3389/fgene.2025.1634202","DOIUrl":"10.3389/fgene.2025.1634202","url":null,"abstract":"<p><p>Microglial cells are key mediators of ethanol-induced neuroinflammation through the release of proinflammatory cytokines and activation of Toll-like receptors. Recently, the signaling pathway initiated by the interaction of the neurotrophic factors pleiotrophin (PTN) and midkine (MK) with receptor-type protein tyrosine phosphatase β/ζ (RPTPβ/ζ) has emerged as a pharmacological target in ethanol-induced neuroinflammatory and neurodegenerative processes. However, the underlying molecular mechanisms remain unclear. In this study, we developed a human co-culture system composed of differentiated SH-SY5Y neuronal cells and HMC3 microglial cells to simulate microglial-neuronal interactions during ethanol exposure. In HMC3 cells, <i>PTN</i> mRNA expression levels were significantly upregulated by ethanol exposure, whereas <i>MK</i> levels were not altered. In contrast, ethanol exposure caused a significant downregulation of <i>MK</i> expression in co-cultures. In general, ethanol increased the expression of inflammatory genes in monocultures of HMC3 cells but not in SH-SY5Y cells. In addition, ethanol exposure caused a highly significant upregulation of <i>TLR3</i> and <i>TLR4</i> in HMC3 cells, which was absent in co-cultures. We also observed a significant attenuation of ethanol-induced increases of inflammatory markers such as <i>IL-1β</i> and <i>CCL2 in</i> co-cultures, indicating the regulatory role of neuronal-microglial interactions. In conclusion, our study provides novel insights into the modulatory actions of microglial-neuronal interactions in ethanol-induced neuroimmune responses and suggests the therapeutic potential of the PTN/RPTPβ/ζ signaling pathway to prevent the deleterious effects of alcohol on the brain.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1634202"},"PeriodicalIF":2.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12412308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omic insights into mitochondrial dysfunction and prostatic disease: evidence from transcriptomics, proteomics, and methylomics.","authors":"Binbin Gong, Feixiang Yang, Ning Zhang, Zhengyang Wu, Tianrui Liu, Kun Wang, Xiangyu Zhang, Yangyang Zhang, Zhengyao Song, Chaozhao Liang","doi":"10.3389/fgene.2025.1609933","DOIUrl":"10.3389/fgene.2025.1609933","url":null,"abstract":"<p><strong>Background: </strong>Prostatic diseases, consisting of prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa), pose significant health challenges. While single-omics studies have provided valuable insights into the role of mitochondrial dysfunction in prostatic diseases, integrating multi-omics approaches is essential for uncovering disease mechanisms and identifying therapeutic targets.</p><p><strong>Methods: </strong>A genome-wide meta-analysis was conducted for prostatic diseases using the genome-wide association studies (GWAS) data from FinnGen and UK Biobank. Mitochondrial dysfunction-related genes were reviewed based on MitoCarta 3.0, with a library containing 1,244 mitochondrial genes. We integrated multi-omics through quantitative trait loci (QTL) across gene expression (eQTLs), protein abundance (pQTLs), and DNA methylation (mQTLs). We prioritized prostatic disease-related mitochondrial genes into three confidence tiers: Tier 1 (two eQTLs + pQTL + mQTL); Tier 2 (two eQTLs + pQTL/mQTL); and Tier 3 (eQTL + pQTL/mQTL). Further mediation analyses were performed to explore potential mediating pathways for the interaction between mitochondrial dysfunction and prostatic diseases, with 1,400 metabolomics and 731 immunomics.</p><p><strong>Results: </strong>We identified DCXR as the gene with Tier 1 evidence for BPH, validated by multi-omics integration through transcriptomic, proteomic, and methylomic signatures. We revealed two Tier 2 genes (NOA1 and ELAC2) and one Tier 3 gene (ACAT1) for BPH, two Tier 3 genes (TRMU and SFXN5) for prostatitis, and six Tier 3 genes (MRPL24, NDUFS6, PUS1, NBR1, GLOD4, and PCBD2) for PCa. We also explored the mediating pathways of mitochondrial genes (within the 3-tiers evidence) on prostatic diseases, and identified 8, 4, and 13 metabolites mediating the interaction between mitochondrial genes and BPH, prostatitis, and PCa, respectively, without the involvement of immune characters.</p><p><strong>Conclusion: </strong>These findings highlight the roles of mitochondrial dysfunction-related genes in prostatic diseases and identify key genes and pathways for potential therapeutic targets.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1609933"},"PeriodicalIF":2.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel pathogenic splicing mutation in <i>COL11A1</i> in a patient with Stickler syndrome verified by minigene splicing assay.","authors":"Jie Zhang, Yaxin Huang, Yafei Deng, Xiaochun Yang, Hong Shi, Yuecheng Yang, Tao Lv, Yuanlong Yan, Ming He, Fang Liu","doi":"10.3389/fgene.2025.1642604","DOIUrl":"10.3389/fgene.2025.1642604","url":null,"abstract":"<p><strong>Background: </strong>Stickler syndrome (STL) is a group of related connective tissue disorders characterized by heterogeneous clinical presentations with varying degrees of orofacial, ocular, skeletal, and auditory abnormalities. However, this condition is difficult to diagnose on the basis of clinical features because of phenotypic variability. Thus, expanding the variant spectrum of this disease will aid in achieving a firm definitive diagnosis of STL.</p><p><strong>Methods: </strong>Comprehensive examinations, including ophthalmology, otology, and orthopedic evaluations, were performed to identify the disease phenotype of the proband. Furthermore, whole-exome sequencing (WES) and Sanger sequencing were performed to identify the molecular basis of the disease. <i>In silico</i> analysis and a minigene splicing assay were conducted to verify the pathogenicity of the splice site variant. The clinical phenotypes of the reported STL patients were then reviewed.</p><p><strong>Results: </strong>The proband presented mild symptoms with early-onset high myopia and mild scoliosis. A novel <i>de novo</i> splicing variant (NM_080629.3: c.4069-1G>T), in the <i>COL11A1</i> gene was identified in the proband via WES and confirmed via Sanger sequencing. Minigene splicing assays verified that this variant resulted in abnormal splicing of the <i>COL11A1</i> transcripts because of the skipping of exon 54 and retention of 21 bp in intron 53. The literature review revealed that the most common phenotypes associated with STL type 2 include myopia and hearing impairment.</p><p><strong>Conclusion: </strong>We identified a novel acceptor splice site variant causing aberrant splicing of <i>COL11A1</i>. Our findings expand the variant spectrum of this gene and provide a precise genetic diagnosis of STL that could be helpful in genetic counseling, reproductive prevention, and treatment of long-term complications of this disorder.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1642604"},"PeriodicalIF":2.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study on dairy goat milk production traits using three models.","authors":"Zhengang Huang, Yuanping Tang, Jianyu Zhou, Dongliang Xu, Xiaokun Lin, Ming Cheng, Jianguang Wang, Qinan Zhao, Jianning He, Xiaoxiao Gao, Jinshan Zhao, Hegang Li","doi":"10.3389/fgene.2025.1650836","DOIUrl":"10.3389/fgene.2025.1650836","url":null,"abstract":"<p><strong>Introduction: </strong>Identifying genetic markers associated with economically important traits in dairy goats helps enhance breeding efficiency, thereby increasing industry value. However, the potential genetic structure of key economic traits in dairy goats is still largely unknown.</p><p><strong>Methods: </strong>This study used three genome-wide association study (GWAS) models (GLM, MLM, FarmCPU) to analyze dairy goat milk production traits (milk yield, fat percentage, protein percentage, lactose percentage, ash percentage, total dry matter, and somatic cell count). The goal was to identify SNPs and positional and functional candidate genes significantly associated with these traits.</p><p><strong>Results: </strong>The GWAS analysis results identified a total of 242 significant SNPs. Among these, 45 SNPs exhibited genome-wide significance, while 197 SNPs demonstrated suggestive associations, corresponding to 99 positional candidate genes within a 50 kb upstream and downstream range. 15 significant SNP loci were consistently identified across all three models, corresponding to 18 candidate genes.The integrated analysis of three models detected 2, 19, 17, 4, 115, 23, and 62 significant SNPs associated with milk yield, ash percentage, protein percentage, lactose percentage, somatic cell count, fat percentage, and total dry matter percentage, respectively. Correspondingly, 6, 24, 9, 12, 37, 14, and 30 candidate genes were identified for these traits. Additionally, several new candidate genes related to milk production traits were proposed (LCORL, TNFRSF1A, VWF, SPATA6, MAN1C1, MASP1, BRCA2).</p><p><strong>Discussion: </strong>In summary, the results of this study provide an important reference for further exploration of the genetic mechanisms underlying dairy goat milk production traits and the development of molecular breeding markers.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1650836"},"PeriodicalIF":2.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A decade of research on genetic privacy: the findings of the GetPreCiSe Center at Vanderbilt University.","authors":"Christopher Slobogin, Karli Tellis, Ellen Wright Clayton, Jay Clayton, Ayden Eilmus, Bradley A Malin","doi":"10.3389/fgene.2025.1629386","DOIUrl":"10.3389/fgene.2025.1629386","url":null,"abstract":"<p><p>Research carried out by Vanderbilt University's and Medical Center's federally-funded transdisciplinary, highly interactive GetPreCiSe Center in Excellence for ELSI research on genomic privacy-involving over 40 scholars across computer and social sciences, law, and the humanities-is summarized by dividing the work into five categories: (1) the nature of risks posed by collection of genetic data; (2) legal and scientific methods of minimizing those risks; (3) methods of safely increasing the scope of genetic databases; (4) public perceptions of genetic privacy; and (5) cultural depictions of genetic privacy. While this research shows that the risk of unauthorized re-identification is often over-stated, it also identifies possible ways privacy can be compromised. Several technical and legal methods for reducing privacy risks are described, most of which focus not on collection of the data, but rather on regulating data security, access, and use once it is collected. Researchers also collected empirical data assessing the public's views on genomic privacy. This research indicated that public concern about genetic privacy may be no greater than concern about financial and other types of privacy and often varies depending on the context in which the information is accessed. More generally, the research suggested that privacy experts may underestimate the extent to which the public values utility over privacy risk. Finally, both survey data and research on media depictions about genetic science found that worry about genetic research and its impact on privacy and other values appear to grow as the time horizon lengthens and varies significantly based on demography; in particular, minority groups defined by ethnicity and sexual identity are more anxious about genetic disclosures than other groups. Research looking at fan fiction, blog posts, and online book reviews also found that these depictions can have a direct impact on public attitudes about genetic science.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1629386"},"PeriodicalIF":2.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Pathogenic <i>PNPLA2</i> variants and nonsense-mediated mRNA decay result in an early-onset neutral lipid storage disease with myopathy.","authors":"Sara Missaglia, Eleonora Martegani, Corrado Angelini, Rita Horvath, Veronika Karcagi, Endre Pal, Daniela Tavian","doi":"10.3389/fgene.2025.1642442","DOIUrl":"10.3389/fgene.2025.1642442","url":null,"abstract":"<p><p>Neutral Lipid Storage Disease with Myopathy (NLSDM) is a rare lipid metabolism disorder caused by impaired Adipose Triglyceride Lipase (ATGL) activity, leading to neutral lipid accumulation in various tissues. It typically manifests with progressive skeletal myopathy, with an onset of around 35 years. In addition, some patients develop cardiomyopathy and liver dysfunction. Herein, we report the molecular characterization of a 27-year-old Hungarian patient and his family in whom two severe <i>PNPLA2</i> mutations led to complete loss of ATGL production in the patient's tissues. DNA sequencing revealed a nonsense (c.24G>A) and a frameshift mutation (c.798dupC) in the <i>PNPLA2</i> gene. RNA analysis showed nonsense-mediated decay of the c.798dupC transcript, while c.24G>A was normally expressed in the patient. However, Western blot analysis did not detect ATGL protein production. From a clinical perspective, our patient exhibited pes planus, proximal muscle weakness of the lower limbs and elevated CK levels from the age of six. MRI and biopsy revealed lipid accumulation, and leukocytes showed Jordans' anomaly. The muscle weakness progressed, and cardiomyopathy and hepatic steatosis were also observed recently. The case highlights two severe <i>PNPLA2</i> mutations leading to complete ATGL deficiency and an unusual early-onset myopathy in childhood.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1642442"},"PeriodicalIF":2.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative genomic insights into adaptation, selection signatures, and population dynamics in indigenous Indian sheep and foreign breeds.","authors":"Malarmathi Muthusamy, Oludayo Michael Akinsola, Pritam Pal, Chitra Ramasamy, Saravanan Ramasamy, Abdulraheem Arome Musa, Aranganoor Kannan Thiruvenkadan","doi":"10.3389/fgene.2025.1621960","DOIUrl":"10.3389/fgene.2025.1621960","url":null,"abstract":"<p><strong>Background: </strong>India's indigenous sheep breeds have evolved under extreme and diverse agro-ecological pressures, yet the genomic basis of their resilience and local adaptation remains poorly understood.</p><p><strong>Method: </strong>This study combines genomic inbreeding estimates, runs of homozygosity (ROH), population structure analyses, and composite selection scans to investigate three native Indian breeds-Changthangi, Deccani, and Garole-within a panel of nine breeds that also includes populations from Africa (Ethiopian Menz), East and South Asia (Tibetan, Chinese Merino, Bangladesh Garole, Bangladesh East), and Europe (Suffolk).</p><p><strong>Results: </strong>ROH and heterozygosity estimates revealed strong contrasts: Bangladesh East sheep exhibited high genomic inbreeding (F_ROH≈14.4%) and low observed heterozygosity (∼30.6%), whereas Deccani sheep showed low inbreeding (F_ROH≈1.1%) and high observed heterozygosity (∼35.6%), consistent with broader gene flow and larger flock sizes. Changthangi and Garole showed moderate inbreeding and distinct ROH length profiles. Population structure analyses confirmed ecological clustering and gene flow shaped by geography and husbandry practices: high-altitude breeds clustered together, while directional migration edges traced admixture from European Suffolk into Changthangi and from Chinese Merino into Ethiopian Menz. Historical effective population sizes showed sharp declines in most breeds, especially those under recent selection. Selection scans identified 118 significant genomic regions across breeds. In Changthangi, key pathways included purinergic signaling, thyrotropin-releasing hormone, and autophagy-consistent with cold and hypoxia adaptation. Deccani showed enrichment for immune adhesion and epidermal regeneration, reflecting parasite resistance and heat stress. Garole displayed signals for gap-junction communication and skeletal development, aligned with high fertility and compact stature.</p><p><strong>Conclusion: </strong>These findings reveal ecotype-pecific adaptive nature shaped by polygenic selection, gene flow, and demography, offering actionable insights for sustainable smallholder breeding strategies.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1621960"},"PeriodicalIF":2.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}