Mammalian Genome最新文献

{"title":"Oncogenic role of LncRNA DLEU2 in thyroid cancer through a NAT10/USP39 regulatory axis.","authors":"Jiwen Yang, Cheng Li, Weili Yin, Fang Fang, Zhiyong Zhao","doi":"10.1007/s00335-026-10225-4","DOIUrl":"10.1007/s00335-026-10225-4","url":null,"abstract":"<p><p>Thyroid cancer incidence is rapidly increasing worldwide, with many patients’ developing radioiodine-refractory disease that leads to a poor prognosis. Long non-coding RNAs (lncRNAs) are critical regulators of tumor progression. While DLEU2 has been implicated in several cancers, its specific function in thyroid cancer remained undefined. This study aimed to investigate the role of DLEU2 in thyroid cancer progression through its interaction with NAT10 and USP39. We examined DLEU2 expression in 70 paired thyroid cancer and adjacent tissues, and in multiple cell lines using qRT-PCR, finding marked upregulation correlated with higher pathological grade and worse survival. Functional assays demonstrated that silencing DLEU2 significantly reduced cell proliferation, migration, and invasion in vitro, while its overexpression produced the opposite effects. Mechanistically, co-immunoprecipitation confirmed that DLEU2 physically interacts with both NAT10 and USP39, and DLEU2 knockdown specifically decreased their protein levels without affecting mRNA expression, suggesting post-translational regulation. These in vitro findings were further validated in vivo, where tumors from DLEU2-silenced xenografts exhibited significantly smaller volume and weight, accompanied by reduced Ki-67 expression. Overall, this study identifies DLEU2 as an oncogenic lncRNA that promotes thyroid cancer progression through stabilization of NAT10 and USP39, highlighting its potential as both a promising biomarker and therapeutic target for clinical intervention.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic-microbial coevolution in human development: chromosome 2 fusion, and human accelerated regions.","authors":"Siddharth Singh, Md Shahadab, Kumar Sachin, Rajan Kumar Pandey, Pankaj Trivedi, Amit Kumar Mishra, Hem Chandra Jha","doi":"10.1007/s00335-026-10228-1","DOIUrl":"10.1007/s00335-026-10228-1","url":null,"abstract":"<p><p>Human-specific traits arise from a confluence of genomic and ecological innovations. A unique telomere-to-telomere fusion of ancestral ape chromosomes produced human chromosome 2 (HSA2), reorganizing the genome and its regulatory landscape. In parallel, hundreds of Human Accelerated Regions (HARs), conserved elements with human-specific sequence changes, became developmental enhancers, and ancient retroviral insertions, namely, endogenous retroviruses (ERVs), were co-opted into promoters and enhancers. Here, we integrate comparative genomics, epigenomics, and host-microbiome co-evolution to propose a unified framework linking these factors to human evolution. We posit that the chromosome 2 fusion reshaped 3D genome architecture and gene regulation. HAR and endogenous retroviral sequences formed composite regulatory modules that drove innovations in cortex development, limb patterning, and immune function. Moreover, host-microbiome co-evolution is woven into this framework, with examples of microbiota-responsive HAR-ERV circuits influencing mucosal immunity, gut-brain signaling, and inflammation.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are we fully exploiting genetic discoveries to understand and treat Alzheimer's disease?","authors":"Julie Williams","doi":"10.1007/s00335-026-10227-2","DOIUrl":"10.1007/s00335-026-10227-2","url":null,"abstract":"","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-type-specific causal effects of CEBPD in CD8 + S100B + Tcells and ZFP36 in monocytes modulate the protective and risk phenotypes in psoriasis.","authors":"Luofei Huang, Jian Shi","doi":"10.1007/s00335-026-10230-7","DOIUrl":"10.1007/s00335-026-10230-7","url":null,"abstract":"<p><p>Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by dysregulated keratinocyte proliferation, immune cell infiltration, and systemic comorbidities. Despite the identification of numerous genetic susceptibility loci for psoriasis through genome-wide association studies (GWAS), their functional roles and underlying causal contributions to psoriasis pathogenesis remain largely unclear. Integrating multi-omics data with causal inference approaches, such as Mendelian randomization (MR), represents a promising strategy for addressing this gap and identifying key regulatory genes. We integrated transcriptome data from the Gene Expression Omnibus database (GEO) database (GSE14905 and GSE30999) and performed weighted gene co-expression network analysis and differential expression analysis to identify psoriasis-related genes. Protein-protein interaction networks and four centrality algorithms (Maximal Clique Centrality (MCC), Maximum Neighborhood Component (MNC), Edge Percolated Component (EPC), and Degree centrality) were applied to identify hub genes, and machine learning methods (least absolute shrinkage and selection operator regression, Random Forest, and artificial neural network) were used to screen diagnostic biomarkers. Immune infiltration analysis was performed using CIBERSORT, and the causal association of signature genes with psoriasis was examined using two-sample MR with single-cell expression quantitative trait locus data from the OneK1K cohort and GWAS summary statistics from FinnGen. Module genes that were significantly associated with psoriasis were identified in our study, among which 19 hub genes were screened. Using machine learning approaches, we further refined these findings to seven signature genes. The diagnostic model based on these seven genes achieved an area under the curve of 0.980. Immune infiltration analysis revealed strong associations between CCAAT/enhancer-binding protein delta (CEBPD) and activated CD4 + memory T cells and follicular helper T cells, and between zinc finger protein 36 (ZFP36) and M1 macrophages. MR analysis demonstrated that higher CEBPD expression in CD8 + S100B + T cells was protective (odds ratio [OR] = 0.795, P = 0.015), whereas higher expression of the ZFP36 gene in monocytes was a risk factor (OR = 1.214, P = 0.043) for psoriasis. Our study identified a robust seven-gene signature with high diagnostic accuracy for psoriasis and provided genetic evidence for the cell type-specific causal role of CEBPD and ZFP36. These findings enhance our understanding of psoriasis pathogenesis and suggest potential targets for developing cell-selective immunomodulatory therapies.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide investigations of the lipid accumulation product index pinpoints polygenic determinants underlying pancreatitis susceptibility.","authors":"Chia-Fu Chien, Zhengwei Qi, Zhengye Liu, Hanze Du, Ziqi Wan, Haotian Chen, Xiaoyin Bai, Jiarui Mi","doi":"10.1007/s00335-026-10215-6","DOIUrl":"10.1007/s00335-026-10215-6","url":null,"abstract":"<p><p>The lipid accumulation product index (LAP) is a robust marker of lipid burden. However, its genetic architecture and causal relevance to pancreatitis remain poorly characterized. We performed a genome-wide association study (GWAS) of LAP in 388,213 European from UK Biobank, followed by colocalization, transcriptome-wide association studies (TWAS), LD score regression and Mendelian randomization for causal relationships. Polygenic risk scores (PRS) were constructed and tested against chronic pancreatitis (CP), hypertriglyceridemic acute pancreatitis (HTG-AP), and acute pancreatitis (AP) using regression models. Gene-environment interactions were evaluated for dietary and lifestyle factors. The GWAS identified 235 independent loci associated with LAP; 18 and 26 genes showed significant colocalization with hepatic and visceral-adipose eQTLs, respectively. TWAS revealed 292 (PrediXcan) and 417 (JTI) genes in visceral fat, and 164 (PrediXcan) and 281 (JTI) in liver, whose expression associated with LAP. Positive genetic correlations were observed between LAP and CP (rg = 0.252) and AP (rg = 0.219). Mendelian randomization supported a causal effect of LAP on CP (β = 6.86 × 10^-3, P = 0.030) and AP (β = 1.68 × 10^-3, P = 0.045). Each 1-SD increase in LAP-PRS conferred higher risk of HTG-AP (OR = 1.11, 95% CI 1.02-1.20) and CP (OR = 1.07, 95% CI 1.00-1.14), but not AP. Furthermore, a healthier dietary pattern can attenuate the HTG-AP risk genetically driven by LAP PRS. This study delineates the polygenic basis of LAP and establishes its causal role in CP and HTG-AP susceptibility, offering a genetically informed indicator for risk assessment of pancreatitis.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AFAP1-AS1 regulates oral squamous cell carcinoma development through the miR-93-3p/CCND1 signaling pathway.","authors":"Kuangzheng Li, Chengwei Li, Qian He, Xiaosheng Fan, Lili Xu, Yixia Jiang","doi":"10.1007/s00335-026-10223-6","DOIUrl":"10.1007/s00335-026-10223-6","url":null,"abstract":"<p><p>Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been found to be closely associated with the initiation and progression of various tumors; however, its role in oral squamous cell carcinoma (OSCC) remains unclear. AFAP1-AS1 expression in OSCC cells was detected using qRT-PCR. The regulatory effects of AFAP1-AS1 on tumor cell proliferation, migration, and invasive capabilities were systematically evaluated through CCK-8 proliferation, colony formation, wound healing, and Transwell invasion assays. Flow cytometry was employed to quantitatively analyze its impact on cell cycle progression and apoptotic. Based on bioinformatics predictions, a dual-luciferase reporter system was utilized to validate the targeting interactions among AFAP1-AS1, miR-93-3p, and CCND1. Functional rescue experiments were conducted to elucidate the functional regulatory network among them. Furthermore, a xenograft tumor model in nude mice was employed to verify in vivo the promoting effect of AFAP1-AS1 on tumor growth. AFAP1-AS1 was significantly upregulated in OSCC cells. AFAP1-AS1 knockdown inhibited the malignant phenotypes of OSCC cells. Mechanistic studies revealed that AFAP1-AS1 could target miR-93-3p and regulate CCND1 expression, thereby influencing OSCC progression. Subcutaneous tumor model in mice further confirmed the in vivo relevance of the AFAP1-AS1/miR-93-3p/CCND1 axis. AFAP1-AS1 downregulation inhibited OSCC progression through the miR-93-3p/CCND1 axis.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping genomic adaptation to environmental heterogeneity in Indian native goat populations through landscape genomics.","authors":"Pallavi Rathi, Nidhi Sukhija, Indrajit Ganguly, S P Dixit, Sanjeev Singh, Chandana Sree Chinnareddyvari, C A Dharaamshaw","doi":"10.1007/s00335-026-10214-7","DOIUrl":"10.1007/s00335-026-10214-7","url":null,"abstract":"<p><p>India harbours a diverse range of indigenous goat breeds that have adapted to varied climatic zones over centuries. This study investigated the genomic basis of local adaptation in these populations (n= 11) divided into seven agro-climatic zones using genome-wide SNP data and century-scale environmental variables. A total of 2,295,833 SNPs and 15 non-collinear bioclimatic predictors were analyzed using the landscape genomics tool R SamBada for genotype-environment association. Models were selected based on G-score and q-value thresholds (q < 0.01). Several loci showed strong signatures of selection, with associated genes enriched in key adaptive pathways, including HIF-1 signalling, insulin signalling, and toll-like receptor pathways. Many key genes and pathways were identified with both direct and indirect roles in adaptation to specific agro-climatic zone. Only 9 SNP variants showed SIFT score < 0.05 (deleterious) out of which, only 2 variants each harbouring gene PTPRC and PLCB1 were predicted to be deleterious with high confidence. Further downstream technical validation for functionality was done using PTPRC and PLCB1 present in coding region and exhibited significant environmental associations. Missense mutations in these genes were further characterized using I-Mutant, ConSurf, and Phyre2. The PTPRC variant was predicted to reduce protein stability within a moderately conserved immune domain, and structural modelling indicated altered folding in mutant proteins. These adaptive variants likely contribute to resilience against heat, humidity, and pathogen-driven stress. This integrative landscape genomics approach reveals how natural selection and environmental pressures have shaped the adaptive genome of Indian indigenous goats and provides a foundation for marker-assisted selection to enhance climate resilience in future breeding programs. This study represents the first landscape genomics analysis in indigenous goat populations of India.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide characterization of HSP70 and HSP90 subfamilies in Yak (Bos grunniens): expression patterns under cold and chemical hypoxia conditions.","authors":"Yufei Zan, Caiwei Ma, Ziqiang Ding, Yi Liu, Fengcheng Song, Yixuan Tang, Jia Li, Liang Du, Xian Guo, Zhengrong Yuan, Yi Ma","doi":"10.1007/s00335-026-10221-8","DOIUrl":"10.1007/s00335-026-10221-8","url":null,"abstract":"<p><p>The yak (Bos grunniens), a typical alpine species, exhibits distinctive adaptations to extreme environments, including a dense coat system and robust tolerance to hypoxia and low temperatures. Within this context, the heat shock protein (HSP) gene family likely plays a core role in the high-altitude adaptive evolution of yaks. By regulating protein homeostasis and mediating cellular stress responses, HSPs critically support cellular physiological functions, particularly under hypoxic and cold stress conditions. The physicochemical properties of the HSP70 and HSP90 subfamilies were systematically evaluated, and their subcellular localization was simulated. Protein-protein interaction (PPI) networks were constructed and RNA sequencing (RNA-seq) data were processed to assess tissue-specific expression patterns in yaks. To evaluate the stress response, yak preadipocyte cells were subjected to cold exposure and chemical hypoxia induction using CoCl2, followed by quantification of HSP70 and HSP90 gene expression using reverse transcription quantitative polymerase chain reaction (RT-qPCR). This genome-wide comparative analysis of HSP70 and HSP90 genes across five bovine species identified four evolutionarily conserved subfamilies exhibiting lineage-specific structural variations, including chromosomal rearrangements and duplication events. In yaks, 14 HSP70/90 genes with different structural configurations and species-specific expression profiles were identified. PPI network analyses revealed novel functional associations between previously uncharacterized HSP members and core regulatory partners. Tissue-specific expression profiling demonstrated ubiquitous HSP gene expression across multiple yak tissues, indicative of a diverse range of physiological functions. Furthermore, the HSP genes exhibited three distinct expression patterns under combined chemical hypoxia induction using cold and CoCl2 stress conditions. This study systematically elucidated the functional significance of HSP genes—particularly HSP70 and HSP90—in the high-altitude adaptation of yaks. Our findings establish a molecular framework for understanding the genetic basis of cold resistance and hypoxia tolerance in bovids, with implications for germplasm improvement.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary biliary cirrhosis and rheumatoid arthritis: a comprehensive study combining genetics and transcriptomics.","authors":"Mingyi Yang, Honghao Ren, Xiaodong Ren, Pengfei Wen, Jiale Xie, Xianjie Wan, Ke Xu, Lin Liu, Weikun Hou, Zhi Yang, Peng Xu","doi":"10.1007/s00335-026-10224-5","DOIUrl":"10.1007/s00335-026-10224-5","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Observational investigations have discerned a correlation between primary biliary cirrhosis (PBC) and rheumatoid arthritis (RA). The primary objective of this study is to elucidate the disease risk correlation between them in terms of genetics, and to explore the genes and signaling pathways involved. We acquired genome-wide association studies (GWAS) summary data for PBC and RA from distinct repositories: PBC data sourced from the IEU OpenGWAS database, and RA data obtained from the Finnish consortium. Employing a bidirectional two-sample Mendelian randomization (MR) approach, we scrutinized the disease risk correlation of PBC and RA. Subsequent to this analysis, we conducted a series of meticulous sensitivity assessments to gauge the robustness of our MR findings. These evaluations encompassed analyses for heterogeneity and horizontal pleiotropy, outlier identification, Leave-One-Out analysis, and assessments for adherence to normal distribution assumptions. Furthermore, we conducted an in-depth analysis of the genes and signaling pathways potentially involved in the disease risk correlation between PBC and RA. Finally, a difference analysis and receiver operating characteristic (ROC) curve analysis were conducted. The MR analysis conducted in this study revealed a significant positive disease risk correlation between PBC and RA (P &lt; 0.001, odds ratio [OR] 95% confidence interval [CI] = 1.081 [1.036-1.128]). Moreover, reverse MR analysis also demonstrated a significant positive disease risk correlation between RA and PBC (P &lt; 0.001, OR 95% CI = 1.702 [1.422-2.039]). Importantly, the bidirectional MR analysis detected no evidence of heterogeneity, horizontal pleiotropy, or outliers, and the results were not affected by single single nucleotide polymorphisms (SNPs). Additionally, the findings were consistent with a normal distribution. SNP-associated gene mapping was performed, identifying 14 candidate genes. Subsequent pathway enrichment analysis indicated that these genes were predominantly involved in the chemokine signaling pathway, JAK-STAT signaling pathway, and Th1/Th2 cell differentiation. Among them, IL12RB2, CCR6, and MANBA may serve as key mediators in the shared disease risk correlation architecture of PBC and RA. Further analysis of the differences identified a gene (MANBA). The ROC curve demonstrated the potential diagnostic value of MANBA. The findings of this study suggest a bidirectional disease risk correlation between PBC and RA, establishing them as mutually risk factors. In clinical practice, vigilance is paramount among patients diagnosed with RA regarding the potential development of PBC. Conversely, individuals presenting with PBC should undergo systematic screening for the presence of RA. The genes and pathways identified in this study as potentially contributing to the mutual disease risk correlation between PBC and RA provide valuable insights and lay the groundwork for future investigations into the underlying mo","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study of mature cow size traits in American Angus cattle.","authors":"Ayooluwa O Ojo, Henrique A Mulim, Milena A F Campos, André Garcia, Kelli Retallick-Riley, Pablo A S Fonseca, Hinayah R Oliveira","doi":"10.1007/s00335-026-10226-3","DOIUrl":"10.1007/s00335-026-10226-3","url":null,"abstract":"<p><p>Mature cow weight (MWT), height (MHT), and body condition score (BCS) are economically important traits that significantly influence cowherd profitability by affecting maintenance feed requirements, which is the largest component of production costs. This study aimed to identify genomic regions, candidate genes, and pleiotropic variants associated with mature cow size traits in American Angus cattle, and to characterize their related gene ontology terms and metabolic pathways. The dataset provided by the American Angus Association comprised 434,746 MWT records from 222,907 animals; 213,875 MHT records from 112,987 animals; and 382,156 BCS records from 209,696 animals. Of these, 45,606 cows were genotyped and imputed to a common marker density of 54,609 markers. A final dataset of 51,410 SNPs from 45,452 animals remained after quality control for further analyses. The single-step genome-wide association study (ssGWAS) method was used in the analyses. Significant associations for mature cow size were detected on BTA7, BTA14, and BTA20, overlapping with previously reported QTLs for growth, feed efficiency, and carcass traits. Candidate genes such as FBXO32, STC2, DUSP1, CREBRF, LAP3, and PENK were found to be related to muscle development, skeletal growth, lipid metabolism, and energy regulation. The genes FBXO32, NTAQ1, ATAD2, DUSP1, ERGIC1, RPL26L1, ATP6V0E1, CREBRF, BNIP1, NKX2-5, and STC2 emerged as candidate genes exhibiting pleiotropic effects on mature cow size traits. Pathway enrichment highlighted the roles of insulin/IGF1R signaling, fibroblast growth factor receptors cascades, and mitogen-activated protein kinase pathways in MWT and MHT, while for BCS, only RHOD GTPase cycle was enriched. Pleiotropy-based analysis of regions affecting mature cow size traits identified shared genomic loci, and subsequent pathway analysis revealed G protein signaling as a common regulatory mechanism linking energy balance, adiposity, and growth. These results contribute to a better understanding of the genomic regions associated with mature cow size traits in Angus cattle.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}