Human Genomics最新文献

{"title":"Hypotrichosis 14: novel variants of the LSS gene in five Chinese families and insights from literature review.","authors":"Yujing Zhang, Mengxi Zhao, Xiangqian Li, Yongping Zhao, Yijie Sun, Jianzhong Zhang, Cong Yu, Cheng Zhou","doi":"10.1186/s40246-025-00798-7","DOIUrl":"https://doi.org/10.1186/s40246-025-00798-7","url":null,"abstract":"<p><strong>Background: </strong>Congenital hypotrichosis 14 is a nonsyndromic form of alopecia associated with pathogenic variants in the lanosterol synthase (LSS) gene. Recent studies have expanded the spectrum of LSS-related phenotypes, including congenital cataracts, alopecia-intellectual disability syndrome, and palmoplantar keratoderma. Currently, investigations into this disease are still limited, and its treatment remains elusive.</p><p><strong>Methods: </strong>In this study, we aimed to report six Chinese patients who were diagnosed with hypotrichosis 14, whose conditions were attributed to five novel and recurrent variants in the LSS gene identified via whole exome sequencing. Moreover, the reported LSS gene has also been summarized.</p><p><strong>Results: </strong>We described six patients in five Chinese families with hair loss, and one of whom had a rare accompanying phenotype of hypergonadotropic hypogonadism, which has rarely been reported. Five novel variants were discovered in the LSS gene, including c.919_921del (p.His307del), c.1987 C > T (p.Arg663Trp), c.982 C > T (p.Arg328*), c.1405_1407del (p.Glu469del) and c.193_200dup (p.Pro68Argfs*14).</p><p><strong>Conclusions: </strong>Our comprehensive summary of phenotypes caused by LSS gene variants not only enriches the existing knowledge on congenital hypotrichosis 14 but also provides crucial guidance for more accurate genetic counseling and potentially new directions for future research in understanding the disease mechanism and developing targeted therapies.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"84"},"PeriodicalIF":3.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between fumarate hydratase variant subtypes and the risk of HLRCC-associated renal cell carcinoma: systematic review and meta-analysis.","authors":"Han Wang, Shamsnur Rehim, Hongjing Wang","doi":"10.1186/s40246-025-00797-8","DOIUrl":"10.1186/s40246-025-00797-8","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"83"},"PeriodicalIF":3.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12282009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BioSTEM: A modern educational tool for research and innovation in the field of molecular biology and personalized medicine.","authors":"George P Patrinos, Stavroula Siamoglou, Konstantinos Lazaros, Vasilios Xirafas, Aristidis G Vrahatis, Christina Mitropoulou","doi":"10.1186/s40246-025-00786-x","DOIUrl":"10.1186/s40246-025-00786-x","url":null,"abstract":"<p><p>Personalized Medicine has the potential to transform modern healthcare by tailoring medical decisions to an individual's unique genomic profile. However, its integration into routine clinical practice is hindered by limited genomics education among healthcare professionals and a general lack of public awareness. To address these challenges, we introduce the BioSTEM initiative, an innovative educational tool designed for primary, elementary, and high school students. BioSTEM combines optimized online learning modules with interactive audiovisual content, fostering direct communication between students and educators. It also integrates alternative learning strategies, such as online games and comics, to enhance engagement with topics in Biology, Molecular Biology, Genetics, and Personalized Medicine. Since 2016, BioSTEM has reached over 6,000 students across three countries through a combination of theoretical instruction and hands-on experiments using a portable molecular biology laboratory. Our results indicate that participation in BioSTEM significantly improved students' and educators' perception of their understanding of concepts in Genetics and Personalized Medicine. Participants reported a stronger grasp of genomic concepts and expressed support for incorporating BioSTEM into the standard biology curriculum. These findings suggest that BioSTEM is a promising and scalable approach to advancing biomedical education and fostering the development of genomic-literate citizens.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"82"},"PeriodicalIF":3.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A scRNA-seq reference contrasting living and early post-mortem human retina across diverse donor states.","authors":"Luning Yang, Yiwen Tao, Qi Pan, Tengda Cai, Yunyan Ye, Jianhui Liu, Yang Zhou, Yongqing Shao, Quanyong Yi, Zen Huat Lu, Lie Chen, Gareth McKay, Richard Rankin, Weihua Meng","doi":"10.1186/s40246-025-00796-9","DOIUrl":"10.1186/s40246-025-00796-9","url":null,"abstract":"<p><strong>Background: </strong>Current human retina studies predominantly utilize post-mortem tissue, and the sample accessibility constraints make the characterization of the living human retina at single-cell resolution a challenge. Although single-nucleus RNA-seq expands the utility of frozen samples, it provides a nuclear-centric view, potentially missing key cytoplasmic information and transient biological processes. Thus, it is important to generate resources directly from living human retinal tissue to complement existing datasets.</p><p><strong>Methods: </strong>We profiled 106,829 single cells from nine unfrozen human retina samples. Living samples were collected within 10 min of therapeutic enucleation and four postmortem samples were collected within 6 h. After standardized dissociation, single-cell transcriptomes were generated using 10x Genomics 3' RNA-seq and applied scVI to generate batch-corrected integrated atlas. Major cell types and subtypes were annotated through iterative Leiden clustering, canonical markers. Subsequent analyses included differential expression comparisons between cell states and regulon activity profiling to further characterize cellular identities and regulatory networks. Transcriptional dynamics were assessed using RNA velocity, and cell-cell signaling pathways were inferred with CellChat. Key findings were validated in independent samples from two additional donors (four samples) using the identical workflow.</p><p><strong>Results: </strong>We contribute to establishing a reference for retinal cell type proportions and cellular states. Our analysis revealed ELF1-mlCone, a distinct cluster of mlCone photoreceptors identified by distinct transcriptional features. The presence and transcriptional features of this cluster were validated in independent samples. Additionally, by comparing living and post-mortem samples, our study highlights differences in transcriptional dynamics: living tissue preserved coherent RNA velocity streams, enabling clear dynamic state transitions, while post-mortem tissue exhibited disorganized patterns. These findings suggest that using living tissue can improve the capture of active cellular states and transitions.</p><p><strong>Conclusions: </strong>Our atlas provides a single-cell reference contrasting living versus early postmortem human retina, integrating cell type composition, transcriptional diversity, and functional insights. It may serve as a useful resource for retinal research and for understanding aspects of human retinal biology, particularly given its inclusion of living tissue and diverse pathological states.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"81"},"PeriodicalIF":3.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Communicating clearly about data sharing in genomics.","authors":"Donrich Thaldar, Diya Uberoi, Adrian Thorogood, Richard Milne, Ainsley J Newson, Alison Hall, David Glazer, Paul Esselaar, Yann Joly","doi":"10.1186/s40246-025-00784-z","DOIUrl":"10.1186/s40246-025-00784-z","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"80"},"PeriodicalIF":3.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-144-3p targeting FLRT3 in osteogenic differentiation of mandibular bone marrow mesenchymal stem cells.","authors":"Jingjun Tian, Chen Lv, Tao Xie, Qi Sun, Changyu Liu, Wen Ma, Chaofeng Liu, Renyi Cheng, Kang Yin, Yanhua Xu","doi":"10.1186/s40246-025-00788-9","DOIUrl":"10.1186/s40246-025-00788-9","url":null,"abstract":"<p><strong>Background: </strong>Fibronectin Leucine-Rich Transmembrane Protein 3 (FLRT3) plays a crucial role in craniofacial development and osteogenic differentiation, yet the regulatory mechanisms of microRNAs (miRNAs) on FLRT3 remain largely unexplored. This study identifies miR-144-3p as a miRNA that targets FLRT3 and investigates its role in osteogenic differentiation. These findings provide a foundation for the development of miRNA-based therapeutic strategies for craniofacial diseases and contribute to a deeper understanding of FLRT3's involvement in osteogenesis.</p><p><strong>Methods: </strong>Mandibular bone marrow mesenchymal stem cells (MBMSCs) were isolated from SD rats using whole bone marrow and limiting dilution techniques. Flow cytometry and differentiation assays for osteogenesis and adipogenesis were conducted to characterize the cells. Bioinformatics analysis was employed to identify miRNAs that regulate FLRT3, with RT-qPCR used to select the most influential miRNA. A dual-luciferase reporter assay was performed to validate the interaction between the miRNAs and FLRT3. RT-qPCR measured miR-144-3p expression during osteogenic induction. Alkaline phosphatase and Alizarin Red S staining were used to assess the role of miR-144-3p in osteogenic differentiation. The impact of miR-144-3p on FLRT3, BMP2, and RUNX2 expression during osteogenesis was further evaluated by RT-qPCR.</p><p><strong>Results: </strong>MBMSCs exhibited spindle-shaped morphology, high purity, and robust proliferative capacity, with flow cytometry confirming positive expression of CD29 and CD90. Bioinformatics analysis identified four miRNAs associated with FLRT3: miR-27a-3p, miR-27b-3p, miR-199a-3p, and miR-144-3p, with miR-144-3p showing the strongest correlation. Dual-luciferase assays confirmed that FLRT3 is a target gene of miR-144-3p. Functional assays revealed that the miR-144-3p mimic decreased FLRT3 expression, while the inhibitor increased it. During osteogenic differentiation, miR-144-3p mimic inhibited osteogenesis, while the inhibitor enhanced it, corresponding to alterations in the expression of FLRT3, BMP2, and RUNX2.</p><p><strong>Conclusion: </strong>miR-144-3p regulates the osteogenic differentiation of MBMSCs by targeting and modulating FLRT3, with FLRT3 being a direct target of miR-144-3p. During osteogenic differentiation, miR-144-3p inhibits osteogenesis by downregulating FLRT3, BMP2, and RUNX2 expression. This study not only elucidates the miRNA-mediated regulatory mechanism in osteogenesis but also offers a novel strategy for mandibular bone defect repair.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"79"},"PeriodicalIF":3.8,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating gut microbiome and neuroplasticity genomics in alcohol use disorder therapy.","authors":"Ilias Koutromanos, Evangelia Legaki, Nikolas Dovrolis, Efthimios Vassilopoulos, Arthur Stem, Vasilis Vasiliou, Elias Tzavellas, Maria Gazouli","doi":"10.1186/s40246-025-00793-y","DOIUrl":"10.1186/s40246-025-00793-y","url":null,"abstract":"<p><strong>Background: </strong>Alcohol Use Disorder (AUD) is a chronic neuropsychiatric condition with substantial public health impact. The interplay between gut microbiota and neuroplasticity-related genes presents a novel approach to understand AUD pathophysiology and treatment response. While microbial dysbiosis has been implicated in AUD, its correlation with gene expression changes in neuroplasticity pathways remains unexplored. This study investigates microbiome composition, microbial metabolic pathways, and their correlation with neuroplasticity-related genes in AUD patients undergoing treatment.</p><p><strong>Methods: </strong>We conducted a prospective observational study integrating gut microbiome 16S rRNA sequencing and host neuroplasticity-related gene expression profiling in AUD patients undergoing treatment which combines psychotherapeutic intervention along with oral diazepam administration followed by Pythagorean Self Awareness Intervention. Patients were classified as responders or non-responders, and microbial composition, functional pathways, and host-microbiota interactions were analyzed using multi-omic correlation frameworks.</p><p><strong>Results: </strong>Responders exhibited a microbiome enriched in short-chain fatty acid (SCFA)-producing bacteria (e.g., Lachnospiraceae), linked to gut barrier integrity and neurotransmitter synthesis. In contrast, non-responders demonstrated enrichment of inflammation-associated taxa (Succinivibrionaceae) and oxidative stress-related metabolic pathways. Correlation analysis revealed microbiome-mediated modulation of neuroplasticity-related genes measured from peripheral blood, including BDNF, GRIA1, CAMK2G, and EGR family genes, suggesting a gut-brain-genomic axis in AUD treatment response.</p><p><strong>Conclusions: </strong>This study highlights the role of gut microbiota as a modulator of neuroplasticity-related gene expression in AUD patients. Integrating microbiome and host genomic signatures could improve biomarker-based prediction of treatment response and inform precision medicine approaches for AUD. Future studies should expand these findings by incorporating multi-omic approaches, including epigenomics and exposomics, to refine microbiome-targeted interventions for addiction therapy.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"78"},"PeriodicalIF":3.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144617397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenome-wide association study identifies multiple traits associated with a polygenic risk score for colorectal cancer.","authors":"Elisabeth A Rosenthal, Wei-Qi Wei, Yuan Luo, Bahram Namjou-Khales, Daniel J Schaid, Edward D Esplin, Michael Lape, Leah Kottyan, Jennifer Allen Pacheco, Chunhua Weng, Adam Samuel Gordon, Iftikhar J Kullo, David R Crosslin, William M Grady, Li Hsu, Ulrike Peters, Gail P Jarvik","doi":"10.1186/s40246-025-00791-0","DOIUrl":"10.1186/s40246-025-00791-0","url":null,"abstract":"<p><strong>Background: </strong>Many factors, including environmental and genetic variables, contribute to Colorectal Cancer (CRC) risk. The genetic components of risk can be divided into monogenic and polygenic factors. Just as monogenic factors can increase risk for more than one condition, polygenic factors may also underlie multiple phenotypes, including behavioral traits. In order to understand the biology of CRC risk better, it is important to understand the shared polygenic genetic architecture contributing to CRC risk and other phenotypes, including CRC associated risk factors.</p><p><strong>Methods: </strong>We investigated potential shared genetics by performing a Phenome-wide association study (PheWAS) with a multi-ancestry CRC polygenic risk score (PRS). The discovery cohort (N = 426,464) consisted of ancestrally diverse participants from the United Kingdom Biobank. The replication cohort (N = 87,271) consisted of ancestrally diverse participants from the electronic Medical Records and Genomics Network phase 3. We used a mixed-effects model to adjust for the presence of related individuals. To preserve power, we limited the number of tests by restricting analysis to ancestor phecodes derived from the electronic health record (EHR) that were not likely to be a result of CRC or its treatment.</p><p><strong>Results: </strong>We discovered and replicated associations between the CRC PRS and breast cancer, prostate cancer, obesity, smoking and alcohol use (discovery p < 1.1e-4; replication p < 0.0019). The association between CRC risk and prostate cancer may be a novel finding, whereas the association with breast cancer has been previously observed using orthogonal methods. The association between CRC risk and behavioral risk factors corroborate previous studies, also using orthogonal methods, and may reveal potential prevention or treatment strategies.</p><p><strong>Conclusions: </strong>As these results corroborate findings from other studies using orthogonal methods, we demonstrate that a CRC PRS can be used as a proxy for genetic risk for CRC when investigating shared genetics between CRC and other phenotypes. Further study of the relationship between PRS from multiple traits with EHR data may reveal additional shared genetic factors. Ultimately, understanding these underlying genetic correlations may identify prevention and treatment strategies for CRC.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"77"},"PeriodicalIF":3.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HerediVar and HerediClassify: tools for streamlining genetic variant classification in hereditary breast and ovarian cancer.","authors":"Anna-Lena Katzke, Marvin Doebel, Jan Hauke, Gunnar Schmidt, Marc Sturm","doi":"10.1186/s40246-025-00787-w","DOIUrl":"10.1186/s40246-025-00787-w","url":null,"abstract":"<p><strong>Background: </strong>Multiple different evidence types as well as gene-specific variant classification guidelines need to be considered during the classification of variants, making the process complex. Therefore, tools that support variant classification by experts are urgently needed.</p><p><strong>Methods: </strong>We present HerediVar a web application and HerediClassify a variant classification algorithm. The performance of HerediClassify was validated and compared to other variant classification tools. HerediClassify implements 19/28 variant classification criteria by the American College of Medical Genetics and gene-specific recommendations for ATM, BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53.</p><p><strong>Results: </strong>HerediVar offers modular annotation services and allows for collaboration in the classification of variants. On the validation dataset, HerediClassify shows an average F1-Score of 93% across all criteria. HerediClassify outperforms other automated variant classification tools like vaRHC and Cancer SIGVAR.</p><p><strong>Conclusion: </strong>In HerediVar and HerediClassify we present a powerful solution to support variant classification in HBOC. Through their modular design, HerediVar and HerediClassify are easily extendable to other use cases and human genetic diagnostics as a whole.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"76"},"PeriodicalIF":3.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared genetic architecture between stroke and blood lipids: a large-scale genome-wide cross-trait analysis.","authors":"Wenya Bai, Guilin Zhou, Huan Jiang, Xuelian Li, Jianlin Shao","doi":"10.1186/s40246-025-00789-8","DOIUrl":"10.1186/s40246-025-00789-8","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"75"},"PeriodicalIF":3.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}