Genome Medicine最新文献

{"title":"Single base focal hypermutation cooccurs with structural variation as an early event in advanced prostate tumourigenesis with ancestry specific independence: a multi-ancestral observational study.","authors":"Jue Jiang, Avraam Tapinos, Ruotian Huang, M S Riana Bornman, Phillip D Stricker, Shingai B A Mutambirwa, David C Wedge, Weerachai Jaratlerdsiri, Vanessa M Hayes","doi":"10.1186/s13073-026-01647-5","DOIUrl":"https://doi.org/10.1186/s13073-026-01647-5","url":null,"abstract":"","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond carrier frequency: a preliminary multicenter study of simultaneous couple-based comprehensive carrier screening for common and rare genetic disorders.","authors":"Bing Xiao, Hongqian Liu, Yu Sun, Xiaotian Su, Xiaoxiao Xie, Zhengfeng Xu, Feng Ren, Ying Peng, Ling Hui, Liangpu Xu, Chunhua Zhang, Jie Duan, Juan Zhang, Juan Li, Shuyuan Xue, Shixiu Liao, Ling Liu, Zhuoshu Zhao, Dejian Yuan, Juan Qiu, Fuqing Zhang, Yang Huang, Yingchun Ha, Lei Yu, Kai Tang, Xiaozhou Li, Wei Pan, Jing Shu, Jiansheng Zhu, Ling Meng, Chenming Xu, Aiping Mao, Nannan Yan, Yongguo Yu","doi":"10.1186/s13073-026-01628-8","DOIUrl":"https://doi.org/10.1186/s13073-026-01628-8","url":null,"abstract":"","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo adenine base editing of mutant Galc gene ameliorates Krabbe disease progression.","authors":"Bae-Geun Nam, Jung Hwa Seo, Sung-Ah Hong, Ju-Hee Kim, Minju Kang, Geneva Rose Notario, Yoontaik Hong, Seunghee Cho, Sangsu Bae, Sung-Rae Cho","doi":"10.1186/s13073-026-01620-2","DOIUrl":"https://doi.org/10.1186/s13073-026-01620-2","url":null,"abstract":"","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"18 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empirical evaluation of analytic validity of polygenic scores.","authors":"Tian Lin, Jian Zeng, Scott D Gordon, Leanne Wallace, Laura Ziser, Sonia Shah, Oliver Pain, Ilja M Nolte, Harold Snieder, Paul A James, Nicholas G Martin, Peter M Visscher, Eric Lee, Loic Yengo, Anjali K Henders, Naomi R Wray","doi":"10.1186/s13073-026-01654-6","DOIUrl":"https://doi.org/10.1186/s13073-026-01654-6","url":null,"abstract":"","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative genomics identifies small interfering RNA with activity against all five human betacoronaviruses.","authors":"Julian Vogler, Shubhankar Ambike, Stoyan Velkov, Cho-Chin Cheng, Pauline Neubecker, Natalie Fischhaber, Pratik Mallick, Ivana Martan, Lucie Sauerhering, Albrecht von Brunn, Ulrike Protzer, Thomas Michler","doi":"10.1186/s13073-026-01659-1","DOIUrl":"https://doi.org/10.1186/s13073-026-01659-1","url":null,"abstract":"","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"18 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allele-specific suppression of pathogenic bestrophin-1 transcripts by CRISPR/Cas9-mediated genome editing.","authors":"Andrea Milenkovic, Bernhard H F Weber","doi":"10.1186/s13073-026-01649-3","DOIUrl":"10.1186/s13073-026-01649-3","url":null,"abstract":"<p><strong>Background: </strong>Treating autosomal dominant gene mutations remains challenging, particularly when mutations convey a gain-of-function or a dominant-negative effect, as standard gene supplementation strategies often fail to counteract the pathogenic allele.</p><p><strong>Methods: </strong>In this study, we employed human induced pluripotent stem cell-derived retinal pigment epithelium (hiPSC-RPE) to investigate allele-specific CRISPR/Cas9 genome editing as a potential treatment for Best disease (BD), an autosomal dominant macular dystrophy caused by over 250 distinct mutations in the bestrophin-1 (BEST1) gene. We designed and evaluated single guide RNAs (sgRNA) targeting three known BEST1 mutations (p.(R218C), p.(A243V), and p.(I295del)), assessing their impact on BD-associated hiPSC-RPE phenotypes and BEST1 channel function. Computationally predicted sgRNAs were rigorously tested for on-target efficiency, allele specificity and genome-wide off-target activities.</p><p><strong>Results: </strong>We found that shortening sgRNA length improved specificity in some cases, while introducing an additional mismatch generally compromised editing efficiency. Notably, only one of the three mutations yielded an sgRNA with both high cleavage efficiency and undetectable off-target effects in hiPSC-RPE cells. We then explored the consequences of allele-specific editing on BEST1 expression and function in clonal BD hiPSC-RPE lines. Eliminating the mutant BEST1 transcript led to enhanced BEST1 localization, improved protein stability and restoration of anion transport function.</p><p><strong>Conclusions: </strong>Taken together, our findings support allele-specific gene editing as a viable therapeutic strategy for selected BEST1 mutations, while underscoring the necessity for rigorous testing of computationally designed sgRNAs, given their mutation- and context-dependent variability.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DposFinder: an interpretable transformer model for predicting phage-derived polysaccharide depolymerases and their host capsular serotypes.","authors":"Yanxiang Shen, Heyuan Lun, Yumeng Zhang, Zhikang Wang, Cui Tai, Xiaohua Chen, Jiangning Song, Ping He, Hong-Yu Ou","doi":"10.1186/s13073-026-01657-3","DOIUrl":"https://doi.org/10.1186/s13073-026-01657-3","url":null,"abstract":"","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent myopic visual exposure triggers myopia progression via H3K27me3.","authors":"Yi Lei, Xiaolei Lin, Xuemei Ling, Yuhan Tan, Jian Yuan, Yating Li, Mengqi Di, Yulu Pan, Lurong Zhong, Zhaoning Feng, Fangfang Jiao, Changxi Hu, Hanyu Deng, Miaozhen Pan, Jianzhong Su, Jia Qu, Wei Chen, Fei Zhao, Xiangtian Zhou","doi":"10.1186/s13073-026-01652-8","DOIUrl":"https://doi.org/10.1186/s13073-026-01652-8","url":null,"abstract":"<p><strong>Background: </strong>Myopia is a global epidemic and a leading cause of visual impairment. It is driven by intermittent environmental exposures, such as near-work, which induce scleral hypoxia. However, the molecular mechanism that translates these transient stimuli into sustained myopia progression remains elusive. We hypothesized that intermittent myopiagenic exposures establish stable pathological changes in the sclera that contribute to myopia development.</p><p><strong>Methods: </strong>We integrated human genetic data from the Myopia Associated Genetics and Intervention Consortium (MAGIC) cohort and the UK Biobank to identify epigenetic factors associated with myopia. Findings were validated in mouse and guinea pig form-deprivation myopia (FDM) models. Intermittent form-deprivation (iFD) protocols were established to investigate how specific epigenetic modifications sustain persistent chromatin remodeling and drive myopia progression. Mechanistic investigations employed Adeno-associated virus serotype 8 (AAV8)-mediated gene knockdown or overexpression, CUT&Tag, RNA-seq, primary human scleral fibroblasts (HSFs) cultures, and protein interaction assays (co-immunoprecipitation and proximity ligation assays).</p><p><strong>Results: </strong>Human myopia genetics reveals significant enrichment of H3K27me3 regulators and targets within myopia-associated loci. FDM models in mice and guinea pigs exhibit an increase in H3K27me3 level and declines in the protein levels of its specific demethylases, KDM6A and KDM6B, in the sclera. Using complementary \"intermittent recovery-based inhibition of myopiagenesis\" and \"intermittent myopiagenic stimulus-induced myopia\" models, we demonstrated that increasing the scleral content of H3K27me3, but not of hypoxia-inducible factor-1α (HIF-1α), is necessary for myopiagenesis. Mechanistically, hypoxia decreases deubiquitinase USP16 content while increasing E3 ligase NEDD4 content, leading to the proteasomal degradation of KDM6A and subsequent H3K27me3 accumulation. Gain or loss of scleral H3K27me3 function, respectively induced or suppressed collagen loss and myopia development. Furthermore, H3K27me3 repressed Sp1 transcription, decreasing scleral collagen content and enabling myopia development.</p><p><strong>Conclusions: </strong>Our findings suggested that scleral H3K27me3 is an epigenetic mediator that connects intermittent myopiagenic exposures to persistent chromatin remodeling and myopia progression. The data support a model involving the \" KDM6A-H3K27me3-Sp1\" axis, providing a molecular framework for understanding the cumulative biological effects of myopiagenic risk factors.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strain-level microbial signatures and inferred functional alterations in infants with food protein-induced allergic proctocolitis.","authors":"Chen Goldstein, Itamar Lavy, Timothy Sun, Dena Ennis, Wayne G Shreffler, Qian Yuan, Yamini V Virkud, Victoria M Martin, Moran Yassour","doi":"10.1186/s13073-026-01646-6","DOIUrl":"10.1186/s13073-026-01646-6","url":null,"abstract":"","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 gene dosage disruption is a key feature and pathogenic mechanism of structural variants in the human genome.","authors":"Xubing Liu, Zhao Chen, Qian Jiang, Haoyu Shen, Hongyu Liu, Zhenguo Wang, Zhe Li, Jihong Wu, Hong Jiang, Xin Li","doi":"10.1186/s13073-026-01653-7","DOIUrl":"https://doi.org/10.1186/s13073-026-01653-7","url":null,"abstract":"","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}