Mammalian Genome最新文献

{"title":"Genomic advancements in goat breeding: enhancing productivity, disease resistance, and sustainability in India's rural economy.","authors":"Manjit Panigrahi, Sonali Sonejita Nayak, Divya Rajawat, Anal Bose, Nishu Bharia, Shivani Das, Anurodh Sharma, Triveni Dutt","doi":"10.1007/s00335-025-10138-8","DOIUrl":"https://doi.org/10.1007/s00335-025-10138-8","url":null,"abstract":"<p><p>Goats are vital to the rural economy of India, contributing significantly to livelihoods, nutrition, and agricultural sustainability. With a population of 148.88 million, India holds the world's largest goat population, comprising 41 recognized indigenous breeds. These goats provide milk, meat, and fiber, particularly in marginal environments. The genomic advancements in goat research have revolutionized the understanding of genetic diversity, adaptation, and trait improvement. Whole-genome sequencing (WGS), single nucleotide polymorphism (SNP) arrays and transcriptomics have unveiled genetic markers associated with production, disease resistance, and reproductive traits. Genomic tools such as the Illumina Goat SNP50K BeadChip and high-throughput sequencing technologies have facilitated the identification of selection signatures and quantitative trait loci (QTL), influencing economically important traits like milk yield, meat quality, and prolificacy. Notably, genes such as DGAT1, GHR, BMPR1B, and HSP70 have been linked to production efficiency, reproductive performance, and climate resilience. Genome-wide association studies (GWAS) and genomic selection (GS) have enabled precision breeding, enhancing genetic gains and reducing inbreeding risks. The application of RNA sequencing has provided insights into gene expression patterns governing lactation, growth, and reproductive efficiency. Epigenomic studies, focusing on DNA methylation and histone modifications, have highlighted regulatory mechanisms underpinning prolificacy and muscle development. Conservation genomics has played a pivotal role in safeguarding native breeds by assessing genetic diversity and mitigating inbreeding depression. Indicine goat breeds, such as Jamunapari, Beetal, Barbari, and Black Bengal, exhibit unique genetic adaptations to diverse agro-climatic conditions, emphasizing the need for their conservation. Emerging technologies, including CRISPR-Cas9 gene editing, hold promise for precision breeding to enhance productivity and disease resistance. Integrating genomics with artificial intelligence (AI) and big data analytics is poised to revolutionize goat breeding and management. Future efforts should focus on expanding genomic databases, developing breed-specific reference genomes, and promoting genomic literacy among farmers to ensure sustainable goat production and improve rural livelihoods in India.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159453","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":"Glycosylated protein-related microenvironmental features in breast cancer are associated with patient prognosis.","authors":"Xiaoxiao Zhong, Jiaxuan Han, Huan Li, Xiangyu Shen, Bowen Yu, Ting Chen, Haobing Li, Jun Li, Jin Pang, Liyuan Qian, Wei Wu, Xiaoliang Tong, Boni Ding","doi":"10.1007/s00335-025-10137-9","DOIUrl":"https://doi.org/10.1007/s00335-025-10137-9","url":null,"abstract":"<p><p>The tumor microenvironment (TME) and aberrant glycosylation have been suggested to play key roles in cancer. This study integrated differentially expressed genes (DEGs) and weighted gene coexpression network analysis (WGCNA) to identify tumor microenvironment-related genes and construct a TME-risk prognostic signature (TMERS) through LASSO Cox regression. After batch effect removal, 44 TME-prognosis-related genes (TMEPGs) were identified and classified into three molecular subtypes via K-means clustering. The finalized 22-gene TMERS model demonstrated robust prognostic predictive capacity in GEO datasets. The results revealed distinct immune profiles and prognostic stratifications among genetic subtypes and risk groups, confirming that the TMERS is an independent prognostic indicator for breast cancer (BRCA). Glycosyltransferase genes (GTs) have potential therapeutic relevance through immune regulation, with TMEPG member killer cell lectin like receptor B1 (KLRB1) significantly correlated with BRCA prognosis. Cellular experiments demonstrated that KLRB1 overexpression suppressed BRCA cell proliferation and migration. This work establishes a novel prognostic model for BRCA while highlighting KLRB1 as a potential biomarker, providing new insights into TME-targeted therapeutic strategies.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135913","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":"Identification of senescence-related biomarkers for osteoporosis based on microarray analysis, Mendelian randomization, and experimental validation.","authors":"Yidong Zhu, Juan Zhao, Zihua Li, Yingqun Chen","doi":"10.1007/s00335-025-10116-0","DOIUrl":"https://doi.org/10.1007/s00335-025-10116-0","url":null,"abstract":"<p><p>Osteoporosis, characterized by decreased bone mineral density, is a common skeletal disorder in the aging population. Cellular senescence is a key factor in the pathophysiology of osteoporosis. This study aimed to identify senescence-related biomarkers and evaluate the functional role in osteoporosis by integrating microarray analysis, Mendelian randomization (MR), and experimental validation. Osteoporosis-related microarray dataset was downloaded from the Gene Expression Omnibus database for differential expression analysis. We integrated summary-level data from genome-wide association studies on osteoporosis with protein quantitative trait loci data to identify genes with causal relationships to osteoporosis. The senescence-related biomarker gene was identified using the SenMayo gene set and evaluated for the predictive performance through receiver operating characteristic (ROC) curve analysis. Functional enrichment analysis was conducted to explore the underlying mechanisms. Validation of gene expression was performed using quantitative real-time PCR in 50 clinical samples from patients with osteoporosis and controls. A total of 33 differentially expressed genes were identified between osteoporosis and control samples. MR analysis revealed 90 genes with causal effects on osteoporosis. Subsequently, CXCL1 was identified as the key senescence-related biomarker gene. ROC curve analysis demonstrated good predictive performance with an area under the curve value of 0.708. Functional enrichment analysis showed a significant association between CXCL1 and immune-related pathways in osteoporosis. The expression of the gene was successfully validated in clinical samples. This study identified and validated CXCL1 as a senescence-related biomarker with causal effects on osteoporosis through a combination of microarray analysis, MR, and experimental validation. These findings offer insights into the molecular mechanisms of osteoporosis and could inform the development of treatment strategies.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135989","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":"Identification of novel gene expression patterns and pathways involved in PARP-1 inhibitor resistance.","authors":"Zulfa Khan, Anish Gomatam, Upadhyayula Suryanarayana Murty, Vaibhav A Dixit","doi":"10.1007/s00335-025-10134-y","DOIUrl":"https://doi.org/10.1007/s00335-025-10134-y","url":null,"abstract":"<p><p>US-FDA has approved PARP-1 inhibitors (Talazoparib, Olaparib, Rucaparib, and Niraparib) as the first line of treatment for many cancer types (e.g., breast, ovarian, pancreatic, and prostate) caused by mutations in breast cancer gene 1 and 2 (BRCA1/2). However, developing resistance to PARP-1 inhibitors is a major concern, which limits therapeutic effectiveness. In the present study, we identified novel gene signatures implicated in developing resistance to Olaparib. Meta-analysis was performed on publicly available RNA-Seq data related to ovarian and breast cancers from the GEO (Gene Expression Omnibus) database. Differential gene expression analysis, gene ontology, KEGG pathway enrichment, and protein-protein interaction (PPI) networking analyses were performed. A total of 139 Common DEGs (Differentially Expressed Genes) were identified, comprising 69 and 70 genes that were upregulated and downregulated respectively. KEGG Pathways \"P53 signaling pathway\" and \"Positive regulation of developmental process(BP)\", \"endoplasmic reticulum lumen(CC),\" and \"growth factor binding(MF)\", were found to be potentially associated with Olaparib resistance. Five hub genes were identified using PPI networking of which FN1, CCN2, and JUN may play a significant role in the development of Olaparib resistance and could be promising therapeutic and diagnostic biomarkers for dealing with Olaparib resistance in BRCA1/2 mutant breast and ovarian cancer.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120101","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":"Snrnp25 is a candidate for the peri-implantation lethal phenotype of the Hba deletions.","authors":"Ana María Velásquez-Escobar, Andrew E Hillhouse, Terry Magnuson, David W Threadgill","doi":"10.1007/s00335-025-10133-z","DOIUrl":"https://doi.org/10.1007/s00335-025-10133-z","url":null,"abstract":"<p><p>Mutations in adult hemoglobin alpha genes in humans lead to blood disorders commonly known as α-thalassemia. In search of a mouse model for this disease, mutagenesis screens have identified several deletions that resemble these phenotypes. The Hba^b2(th) deletion, in particular, replicates the characteristics of alpha-thalassemia minor in heterozygous mice but presents a homozygous embryonic lethal phenotype. Previous analyses of Hba^b2(th) mice suggested that the deletion affects both Hba genes (Hba-a1 and Hba-a2) and considered epidermal growth factor receptor (Egfr) or rhomboid 5 homolog 1 (Rhbdf1) to be responsible for the embryonic lethality. Molecular analysis of Hba^b2(th) revealed a deletion spanning a 1 cM region of mouse chromosome 11. Importantly, the Hba^b2(th) deletion does not extend to Egfr, indicating that the observed lethality of homozygous embryos is not due to the loss of Egfr. Sequence analysis of the Hba^b2(th) deletion showed that the Hba-a2 gene is not deleted, but the lack of expression is likely due to the disruption of upstream regulatory regions. Furthermore, we identify Snrnp25, which codes for the small nuclear ribonucleoprotein 25 (U11/U12), as the candidate gene most likely responsible for the peri-implantation lethality of Hba^b2(th) homozygous mice. These findings enhance the understanding of the genetic mechanisms underlying α-thalassemia and provide insights into novel genes essential for early mammalian development.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120103","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":"Genetic and immune landscape of keratoconus: insights from Mendelian randomization analysis.","authors":"Yuhui Yu, Qiang Liu, Chen Zhou, Juan Jiang, Yanchun Li","doi":"10.1007/s00335-025-10135-x","DOIUrl":"https://doi.org/10.1007/s00335-025-10135-x","url":null,"abstract":"<p><p>This study aimed to identify key genes and immune features associated with keratoconus (KC), a progressive eye disorder, by integrating genomic and transcriptomic data using Mendelian randomization (MR) methods. We employed summary data-based Mendelian randomization (SMR) and inverse-variance weighted Mendelian randomization (IVW-MR) to analyze genetic variations from public databases. The study included expression quantitative trait loci (eQTL) data for 16,987 genes and GWAS summary statistics for 19,942 gene traits and 731 immune traits. We also utilized gene expression data from keratoconus patients and controls to validate findings and explore causal relationships. We identified 715 genes associated with KC, including 371 risk genes and 344 protective genes. Pathway over-representation analyses indicated that risk genes are involved in the regulation of the cytoskeleton, while protective genes are related to metabolic processes. Differential expression analysis showed significant overexpression of risk genes in KC samples. Additionally, we found 21 immune phenotypes with causal effects on KC, highlighting the role of immune cells in the disease's pathogenesis. The study revealed multiple risk and protective genes linked to KC, providing new insights into its pathophysiological mechanisms. The findings underscore the importance of cytoskeletal remodeling and immune regulation in KC and suggest potential targets for future diagnostic and therapeutic strategies. Further research is needed to validate these genes and immune traits' functions and their clinical application potential.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086474","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":"Transforming beef quality through healthy breeding: a strategy to reduce carcinogenic compounds and enhance human health: a review.","authors":"Belete Kuraz Abebe, Juntao Guo, Diba Dedacha Jilo, Jianfang Wang, Shengchen Yu, Haibing Liu, Gong Cheng, Linsen Zan","doi":"10.1007/s00335-025-10129-9","DOIUrl":"https://doi.org/10.1007/s00335-025-10129-9","url":null,"abstract":"<p><p>The presence of carcinogenic substances in beef poses a significant risk to public health, with far-reaching implications for consumer safety and the meat production industry. Despite advancements in food safety measures, traditional breeding methods have proven inadequate in addressing these risks, revealing a substantial gap in knowledge. This review aims to fill this gap by evaluating the potential of healthy breeding techniques to significantly reduce the levels of carcinogenic compounds in beef. We focus on elucidating the molecular pathways that contribute to the formation of key carcinogens, such as heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs), while exploring the transformative capabilities of advanced genomic technologies. These technologies include genomic selection, CRISPR/Cas9, base editing, prime editing, and artificial intelligence-driven predictive models. Additionally, we examine multi-omics approaches to gain new insights into the genetic and environmental factors influencing carcinogen formation. Our findings suggest that healthy breeding strategies could markedly enhance meat quality, thereby offering a unique opportunity to improve public health outcomes. The integration of these innovative technologies into breeding programs not only provides a pathway to safer beef production but also fosters sustainable livestock management practices. The improvement of these strategies, along with careful consideration of ethical and regulatory challenges, will be crucial for their effective implementation and broader impact.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008167","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":"Complementarity and integration of animal and in vitro non-animal pre-clinical model systems- an Australian perspective.","authors":"Ruth M Arkell, Ernst J Wolvetang, Twishi Gulati, James E Hennessy, Adam P Hill, Thierry Jardé, Andrew J Kueh, Paul Q Thomas, Louise N Winteringham, Michael S Dobbie","doi":"10.1007/s00335-025-10132-0","DOIUrl":"https://doi.org/10.1007/s00335-025-10132-0","url":null,"abstract":"<p><p>Recent advances in the development of pre-clinical models based on non-animal technologies (NATs) have stimulated expectations that the use of animals in research may soon be phased out. The true value of innovations in NATs and their applications lies, however, in enabling an expanded and integrated portfolio of complementary animal and non-animal model systems to improve the accuracy and efficiency of pre-clinical research and therapeutic development. The term NATs covers a range of techniques spanning in silico, cell free, organ-on-chip as well as in vitro techniques including three-dimensional cell culture models termed organoids. Of these, in vitro systems are currently the most broadly used in biomedicine laboratories and are the first NATs for which Australia has invested in nationwide support. The focus of this commentary is the importance of understanding the strengths and limitations of in vitro and animal models such that an integrated portfolio of complementary genetic models continues to evolve to best support pre-clinical research and therapeutic development pipelines.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020720","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":"Challenges of modelling TDP-43 pathology in mice.","authors":"José Miguel Brito Armas, Lucas Taoro-González, Elizabeth M C Fisher, Abraham Acevedo-Arozena","doi":"10.1007/s00335-025-10131-1","DOIUrl":"https://doi.org/10.1007/s00335-025-10131-1","url":null,"abstract":"<p><p>TDP-43 is a normally nuclear RNA binding protein that under pathological conditions may be excluded from the nucleus and deposited in the cytoplasm in the form of insoluble polyubiquitinated and polyphosphorylated inclusions. This nuclear exclusion coupled with cytoplasmic accumulation is called TDP-43 pathology and contributes to a range of disorders collectively known as TDP-43 proteinopathies. These include the great majority of amyotrophic lateral sclerosis (ALS) cases, all limbic-predominant age-related TDP-43 encephalopathy (LATE), as well as up to 50% of frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) cases. Thus, TDP-43 pathology is a common feature underlying a wide range of neurodegenerative conditions. However, modelling it has proven to be challenging, particularly generating models with concomitant TDP-43 loss of nuclear function and cytoplasmic inclusions. Here, focussing exclusively on mice, we discuss TDP-43 genetic models in terms of the presence of TDP-43 pathology, and we consider other models with TDP-43 pathology due to mutations in disparate genes. We also consider manipulations aimed at producing TDP-43 pathology, and we look at potential strategies to develop new, much needed models to address the many outstanding questions regarding how and why TDP-43 protein leaves the nucleus and accumulates in the cytoplasm, causing downstream dysfunction and devastating disease.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015811","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":"Alpha-synuclein pathology and Parkinson's disease-related olfactory dysfunctions: an update on preclinical models and therapeutic approaches.","authors":"Jancy Nixon Abraham, Devesh Rawat, Priyadharshini Srikanth, Lisni P Sunny, Nixon M Abraham","doi":"10.1007/s00335-025-10128-w","DOIUrl":"https://doi.org/10.1007/s00335-025-10128-w","url":null,"abstract":"<p><p>Olfactory dysfunction (OD) is considered one of the early signs of Parkinson's disease (PD), affecting over 90% of PD patients. OD often appears several years before the onset of motor symptoms and is therefore considered an early biomarker of PD. Recent studies have shown that COVID-19 infection might lead to worsening of symptoms and acceleration of disease progression in neurodegenerative disorders, where OD is a common symptom to both. Hence, it is essential to accurately monitor olfactory fitness in clinical settings using any of the currently available olfactory function tests. Even after a quarter of a century of the discovery of α-synuclein (α-syn) pathogenesis in PD, many aspects related to the α-syn pathogenesis in OD remain unknown. Currently, there is no definitive cure for PD; the disease management options include dopaminergic medications, deep brain stimulations, stem cells, and immunotherapy. Generating reliable PD animal models is critical for understanding the molecular pathways and neural circuits affected by disease conditions. This might contribute to the development and validation of new therapeutic approaches. This review discusses the known mechanisms of α-syn aggregated forms causing neuronal death, the recent developments in the PD preclinical models with ODs, and the treatment strategies employed.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027608","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}