Mammalian Genome最新文献

{"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":"<p><p>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 < 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 < 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":2.7,"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":"","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"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}

{"title":"Assessment of genome-wide genetic variability and population divergence of four native Turkish sheep breeds.","authors":"Bahar Argun Karslı, Eymen Demir, Umit Bilginer, Taki Karslı, Sarp Kaya, Huriye Doğru, Irmak Kara, Veli Atmaca, Duygu Kaşıkçı, Serdar Koçak, Serdar Yağcı, Murat Soner Balcıoğlu, Emiliano Lasagna, Fetih Gülyüz","doi":"10.1007/s00335-026-10213-8","DOIUrl":"10.1007/s00335-026-10213-8","url":null,"abstract":"<p><p>Genetic variability is crucial for enhancing economically important traits and for developing effective conservation strategies in livestock populations. In this study, genome-wide genetic variability and population divergence were evaluated in four native Turkish sheep breeds, known as Dağlıç (DGL), Sakız (SKZ), Pırlak (PRL), and Pırıt (PRT), using 366,544 single nucleotide polymorphisms (SNPs) generated by double-digest restriction-site associated DNA sequencing (ddRADseq). Across the four populations, the mean minor allele frequency (MAF) and nucleotide diversity (π) were estimated at 0.320 and 0.295, respectively. Observed heterozygosity (H_O) ranged from 0.314 in the DGL breed to 0.323 in the SKZ breed. Expected heterozygosity (H_E) values were consistently higher than the observed values across all breeds, with an overall mean of 0.327. The inbreeding coefficient (F_IS) was negative in all populations, varying from - 0.034 in PRL to - 0.019 in DGL. Population structure analyses based on discriminant analysis of principal components (DAPC), ADMIXTURE, and TreeMix revealed a high level of admixture between the PRL and PRT populations, whereas the DGL breed was genetically distinct. In addition, TreeMix inferred a migration edge from the SKZ breed to the PRL-PRT clade. The high level of genetic variability observed in native Anatolian sheep breeds should be conserved to support diverse breeding strategies and to mitigate potential future challenges, particularly genetic bottlenecks. Further studies employing improved sampling strategies are recommended to obtain more robust insights into the genetic structure of native Anatolian sheep, especially for the PRL and PRT populations.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623279","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":"Tissue-specific transcriptional epistasis between Prkn and Lrrk2 during mycobacterial infection.","authors":"Monica Dallmann-Sauer, Yong Zhong Xu, Wilian Correa-Macedo, Marianna Orlova, Erwin Schurr","doi":"10.1007/s00335-026-10219-2","DOIUrl":"https://doi.org/10.1007/s00335-026-10219-2","url":null,"abstract":"","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593080","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":"Integrative immunogenomic and experimental characterization reveals CXCL9, CXCL13, CCL5 and CD74 as key oncogenic drivers in breast cancer.","authors":"Mohammed A Alshehri, Mohammed Alissa","doi":"10.1007/s00335-026-10218-3","DOIUrl":"10.1007/s00335-026-10218-3","url":null,"abstract":"<p><p>Breast cancer remains the most prevalent malignancy among women worldwide, driven by complex interactions between tumor-intrinsic factors and the immune microenvironment. Understanding immune-related molecular regulators is essential to improve diagnostic and therapeutic strategies. Transcriptomic data from the TCGA-BRCA dataset (1109 tumor and 113 normal samples) were analyzed to identify differentially expressed immune-related genes by cross-referencing ImmPort and InnateDB gene sets. Protein-protein interaction networks were constructed using STRING and Cytoscape to identify hub genes. Validation analyses were conducted using GSCA, cBioPortal, and GEO datasets. miRNA-mRNA regulatory interactions were explored using TargetScan, miRDB, miRWalk, and miRTarBase databases, followed by dual-luciferase reporter assays. Functional characterization of CCL5 and CD74 was performed through siRNA-mediated knockdown in breast cancer cell lines, proliferation, colony formation, and wound healing assays, as well as xenograft mouse models. Four key immune-related hub genes, including CXCL9, CXCL13, CCL5, and CD74 were identified as significantly upregulated in breast cancer. Epigenetic and prognostic analyses revealed that these genes were influenced by promoter methylation and correlated with poor survival outcomes. miRNA-mRNA network analysis identified hsa-miR-146a-5p and hsa-miR-200c-3p as central regulators, validated by luciferase assays. Functional studies showed that silencing CCL5 and CD74 significantly reduced cell proliferation, migration, and tumor growth in vivo, confirming their oncogenic roles. This integrative multi-omics and experimental study identified CCL5 and CD74 as key immune-oncogenic drivers of breast cancer progression. Their modulation of the MIF-CD74 signaling axis highlights potential therapeutic targets for immunomodulatory interventions and combination therapy in breast cancer.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593005","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":"Unravelling male infertility through epigenetics: present understanding and future challenges.","authors":"S Amrita Malini, Almitra Abhijit Dravid, Ritwika Saha, Abilash Valsala Gopalakrishnan, Sandra Kannampuzha","doi":"10.1007/s00335-026-10217-4","DOIUrl":"https://doi.org/10.1007/s00335-026-10217-4","url":null,"abstract":"","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593033","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":"Hongwu mixture exerts inhibition on triple-negative breast cancer by regulating SAV1/Hippo signaling through ZNF143.","authors":"Aiping Wu, Jun Ma, Qiong Wang, Aifei Chen, Wenling Lv, Yu Zhang, Hongying Zhang","doi":"10.1007/s00335-026-10220-9","DOIUrl":"10.1007/s00335-026-10220-9","url":null,"abstract":"<p><p>Hongwu mixture (HWM) consists of Taxus chinensis, Marsdenia tenacissima, Rhizoma Curcumae, and Semen coicis. The objective of this study was to ascertain the potential role of the Hongwu mixture (HWM) in the treatment of triple-negative breast cancer (TNBC). TNBC cells were treated with low, medium, and high doses of HWM, and CCK-8 assays were conducted to evaluate the impact of different doses of HWM on TNBC cell viability. The target molecules of HWM were predicted using RNA-sequencing, and molecular docking models between HWM components and target proteins were developed. As the dose of HWM increased, TNBC cell viability gradually decreased. HWM inhibited the proliferation and mobility of TNBC cells, slowed the tumor growth, and upregulated the apoptosis of TNBC cells. HWM promoted Zinc finger protein 143 (ZNF143)-mediated transcriptional activation of salvador family WW domain-containing protein 1 (SAV1) by stabilizing ZNF143 protein expression, leading to phosphorylation of large tumor suppressor homolog 1 (LATS1) and Yes-associated protein 1 (YAP1). Knockdown of ZNF143/SAV1 signaling impaired the therapeutic effect of HWM, and treatment with verteporfin, pharmacological inhibition of YAP/TAZ, reversed the effects of knockdown of SAV1. Therefore, HWM might offer a potent strategy for managing TNBC effectively.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147530052","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":"Comprehensive bioinformatics analysis and experimental validation reveal the role of circadian rhythm-related genes in the crosstalk between osteoporosis and atherosclerosis.","authors":"Tengyan Liu, Jiashuang Fan, Jianyun Fang, Zhuan Qu, Yaxin He, Kai Yang, Jianlin Yang, Juye Zhang, Dan Yang, Lifen Dai","doi":"10.1007/s00335-026-10216-5","DOIUrl":"10.1007/s00335-026-10216-5","url":null,"abstract":"<p><p>Osteoporosis (OP) and atherosclerosis (AS) are increasingly prevalent in aging populations and frequently coexist, sharing pathological features such as abnormal vascular calcification. However, the common marker genes underlying the crosstalk between OP and AS remain poorly understood. This study aimed to identify shared marker genes and cellular mechanisms contributing to the coexistence of OP and AS. Single-cell RNA sequencing (scRNA-seq) dataset and mRNA expression profiles related to OP and AS were obtained from the Gene Expression Omnibus (GEO) database. Bioinformatics analyses were performed using the R packages Seurat, AUCell, and hdWGCNA to identify circadian rhythm-related genes (CRGs) and associated cell populations. Naturally aged mice and a 0.25% adenine (AD)-induced mouse model were established. Micro-computed tomography (µCT), immunohistochemistry (IHC), immunofluorescence, Von Kossa staining, and RT-qPCR were conducted to experimentally validate the identified common genes. In human bone marrow samples, nine cell lineages comprising 17 subpopulations were identified, while six cell lineages comprising 18 subpopulations were identified in carotid artery samples. Circadian rhythm activity was significantly enriched in bone marrow stromal cells (BMSCs) in OP and vascular smooth muscle cells (VSMCs) in AS. By integrating scRNA-seq and bulk RNA-seq analyses, 69 common genes were identified, of which 15 hub genes were further selected through protein-protein interaction (PPI) network analysis. Experimental validation demonstrated that AEBP1 was markedly upregulated in both naturally aged and AD-induced mice, accompanied by increased PLIN1 expression, reduced osteocalcin (OCN) expression, and enhanced vascular calcification. This study reveals that circadian rhythm-related regulation of BMSCs in OP and VSMCs in AS plays a critical role in their coexistence. Furthermore, we identify shared marker genes, particularly AEBP1, which may serve as potential biomarkers and therapeutic targets for the concurrent development of OP and AS.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147530022","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":"Vascular contribution to cognitive impairment and dementia (VCID): proceedings of 2025 workshop of the Jackson Laboratory.","authors":"Mehwish Anwer, Tetiana Poliakova, Ricardo D'Oliveira Albanus, Mohammad Iqbal H Bhuiyan, Adam M Brickman, Soumilee Chaudhuri, Leah Cuddy, Maxwell Eisenbaum, Kate Foley, Douglas B Gould, Catherine Hall, Costantino Iadecola, Olivia Marola, Christopher M Norris, Alaina Reagan, Julie Schneider, Donna Wilcock, Isabella Xu, Andrew Yang, Gareth Howell, Cheryl L Wellington","doi":"10.1007/s00335-026-10210-x","DOIUrl":"10.1007/s00335-026-10210-x","url":null,"abstract":"<p><p>The first Vascular Contributions to Cognitive Impairment and Dementia (VCID) Workshop, held on May12-16, 2025 at The Jackson Laboratory, provided scientific content and career development training in the latest developments in VCID and Alzheimer's Disease (AD) and related dementia (ADRD). The Workshop aimed to foster interdisciplinary collaborations and empower the next generation of diverse scientists to advance ADRD research from mechanism to intervention. The meeting placed a strong emphasis on neurovascular pathology, its central role in ADRD pathogenesis, its modulation by both central and peripheral factors, and the critical need to dissect the mechanistic basis of VCID through experimental models. The workshop included talks from both faculty and trainees and was bookended by two keynote addresses by Drs. Donna Wilcock and Costantino Iadecola, leaders and pioneers in the VCID field. The second VCID workshop is planned for April 28-May 1, 2026, to be held at Washington University in St. Louis.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147458315","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":"Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminants.","authors":"U A Rossi, M E Caffaro, D N Gaute, M R Castaño, E Maurizio, M A Poli, C A Rossetti","doi":"10.1007/s00335-026-10212-9","DOIUrl":"https://doi.org/10.1007/s00335-026-10212-9","url":null,"abstract":"","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147458345","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}