Nature genetics最新文献

{"title":"Somatic mutations in the stomach","authors":"Safia Danovi","doi":"10.1038/s41588-025-02181-7","DOIUrl":"10.1038/s41588-025-02181-7","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 4","pages":"774-774"},"PeriodicalIF":31.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813799","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":"The PCOS-endometrial cell atlas","authors":"Chiara Anania","doi":"10.1038/s41588-025-02180-8","DOIUrl":"10.1038/s41588-025-02180-8","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 4","pages":"774-774"},"PeriodicalIF":31.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813772","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":"Genetics of coronary artery dominance","authors":"Kyle Vogan","doi":"10.1038/s41588-025-02179-1","DOIUrl":"10.1038/s41588-025-02179-1","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 4","pages":"774-774"},"PeriodicalIF":31.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813773","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":"A redefined InDel taxonomy provides insights into mutational signatures","authors":"Gene Ching Chiek Koh, Arjun Scott Nanda, Giuseppe Rinaldi, Soraya Boushaki, Andrea Degasperi, Cherif Badja, Andrew Marcel Pregnall, Salome Jingchen Zhao, Lucia Chmelova, Daniella Black, Laura Heskin, João Dias, Jamie Young, Yasin Memari, Scott Shooter, Jan Czarnecki, Matthew Arthur Brown, Helen Ruth Davies, Xueqing Zou, Serena Nik-Zainal","doi":"10.1038/s41588-025-02152-y","DOIUrl":"10.1038/s41588-025-02152-y","url":null,"abstract":"Despite their deleterious effects, small insertions and deletions (InDels) have received far less attention than substitutions. Here we generated isogenic CRISPR-edited human cellular models of postreplicative repair dysfunction (PRRd), including individual and combined gene edits of DNA mismatch repair (MMR) and replicative polymerases (Pol ε and Pol δ). Unique, diverse InDel mutational footprints were revealed. However, the prevailing InDel classification framework was unable to discriminate these InDel signatures from background mutagenesis and from each other. To address this, we developed an alternative InDel classification system that considers flanking sequences and informative motifs (for example, longer homopolymers), enabling unambiguous InDel classification into 89 subtypes. Through focused characterization of seven tumor types from the 100,000 Genomes Project, we uncovered 37 InDel signatures; 27 were new. In addition to unveiling previously hidden biological insights, we also developed PRRDetect—a highly specific classifier of PRRd status in tumors, with potential implications for immunotherapies. This paper describes a framework for classifying small insertions and deletions from genomic data and applies it to a large dataset comprising seven tumor types. The analysis highlights new insertion and deletion signatures and a classifier of postreplicative repair dysfunction.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 5","pages":"1132-1141"},"PeriodicalIF":31.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-025-02152-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813663","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":"Solanum pan-genome highlights paralog diversification","authors":"Wei Li","doi":"10.1038/s41588-025-02178-2","DOIUrl":"10.1038/s41588-025-02178-2","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 4","pages":"774-774"},"PeriodicalIF":31.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813771","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":"Mutations in the small nuclear RNA gene RNU2-2 cause a severe neurodevelopmental disorder with prominent epilepsy","authors":"Daniel Greene, Koenraad De Wispelaere, Jon Lees, Marta Codina-Solà, Brynjar O. Jensson, Emma Hales, Andrea Katrinecz, Esther Nieto Molina, Sonia Pascoal, Rolph Pfundt, Rachel Schot, Marta Sevilla Porras, Frank Sleutels, Irene Valenzuela, Robin Wijngaard, Ignacio Arroyo Carrera, Giles Atton, Didac Casas-Alba, Deirdre Donnelly, Anna Duat Rodríguez, Bárbara Fernández Garoz, Nicola Foulds, Deyanira García-Navas Núñez, Elena González Alguacil, Joanna Jarvis, Sarina G. Kant, Irene Madrigal Bajo, Antonio F. Martinez-Monseny, Shane McKee, Nelmar Valentina Ortiz Cabrera, Laia Rodríguez-Revenga Bodi, Andrea Sariego Jamardo, Kari Stefansson, Patrick Sulem, Mohnish Suri, Clara Van Karnebeek, Pradeep Vasudevan, Ana Isabel Vega Pajares, Ángel Carracedo, Marc Engelen, Pablo Lapunzina, Natasha P. Morgan, Beatriz Morte, Patrick Rump, Kathy Stirrups, Eduardo F. Tizzano, Tahsin Stefan Barakat, Michael O’Donoghue, Luis Alberto Pérez-Jurado, Kathleen Freson, Andrew D. Mumford, Ernest Turro","doi":"10.1038/s41588-025-02159-5","DOIUrl":"10.1038/s41588-025-02159-5","url":null,"abstract":"The major spliceosome includes five small nuclear RNA (snRNAs), U1, U2, U4, U5 and U6, each of which is encoded by multiple genes. We recently showed that mutations in RNU4-2, the gene that encodes the U4-2 snRNA, cause one of the most prevalent monogenic neurodevelopmental disorders. Here, we report that recurrent germline mutations in RNU2-2 (previously known as pseudogene RNU2-2P), a 191-bp gene that encodes the U2-2 snRNA, are responsible for a related disorder. By genetic association, we identified recurrent de novo single-nucleotide mutations at nucleotide positions 4 and 35 of RNU2-2 in nine cases. We replicated this finding in 16 additional cases, bringing the total to 25. We estimate that RNU2-2 syndrome has a prevalence of ~20% that of RNU4-2 syndrome. The disorder is characterized by intellectual disability, autistic behavior, microcephaly, hypotonia, epilepsy and hyperventilation. All cases display a severe and complex seizure phenotype. We found that U2-2 and canonical U2-1 were similarly expressed in blood. Despite mutant U2-2 being expressed in patient blood samples, we found no evidence of missplicing. Our findings cement the role of major spliceosomal snRNAs in the etiologies of neurodevelopmental disorders. Recurrent de novo mutations at nucleotide positions 4 and 35 of RNU2-2 cause a neurodevelopmental disorder whose prominent features include intellectual disability, developmental delay and a complex seizure phenotype.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1367-1373"},"PeriodicalIF":31.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-025-02159-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813664","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":"Author Correction: Identification of genetic elements that autonomously determine DNA methylation states","authors":"Florian Lienert, Christiane Wirbelauer, Indrani Som, Ann Dean, Fabio Mohn, Dirk Schübeler","doi":"10.1038/s41588-025-02185-3","DOIUrl":"10.1038/s41588-025-02185-3","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 5","pages":"1320-1320"},"PeriodicalIF":31.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-025-02185-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813632","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":"Genetic regulation of gene expression across multiple tissues in chickens","authors":"Dailu Guan, Zhonghao Bai, Xiaoning Zhu, Conghao Zhong, Yali Hou, Di Zhu, The ChickenGTEx Consortium, Houcheng Li, Fangren Lan, Shuqi Diao, Yuelin Yao, Bingru Zhao, Xiaochang Li, Zhangyuan Pan, Yahui Gao, Yuzhe Wang, Dong Zou, Ruizhen Wang, Tianyi Xu, Congjiao Sun, Hongwei Yin, Jinyan Teng, Zhiting Xu, Qing Lin, Shourong Shi, Dan Shao, Fabien Degalez, Sandrine Lagarrigue, Ying Wang, Mingshan Wang, Minsheng Peng, Dominique Rocha, Mathieu Charles, Jacqueline Smith, Kellie Watson, Albert Johannes Buitenhuis, Goutam Sahana, Mogens Sandø Lund, Wesley Warren, Laurent Frantz, Greger Larson, Susan J. Lamont, Wei Si, Xin Zhao, Bingjie Li, Haihan Zhang, Chenglong Luo, Dingming Shu, Hao Qu, Wei Luo, Zhenhui Li, Qinghua Nie, Xiquan Zhang, Ruidong Xiang, Shuli Liu, Zhe Zhang, Zhang Zhang, George E. Liu, Hans Cheng, Ning Yang, Xiaoxiang Hu, Huaijun Zhou, Lingzhao Fang","doi":"10.1038/s41588-025-02155-9","DOIUrl":"10.1038/s41588-025-02155-9","url":null,"abstract":"The chicken is a valuable model for understanding fundamental biology and vertebrate evolution and is a major global source of nutrient-dense and lean protein. Despite being the first non-mammalian amniote to have its genome sequenced, a systematic characterization of functional variation on the chicken genome remains lacking. Here, we integrated bulk RNA sequencing (RNA-seq) data from 7,015 samples, single-cell RNA-seq data from 127,598 cells and 2,869 whole-genome sequences to present a pilot atlas of regulatory variants across 28 chicken tissues. This atlas reveals millions of regulatory effects on primary expression (protein-coding genes, long non-coding RNA and exons) and post-transcriptional modifications (alternative splicing and 3′-untranslated region alternative polyadenylation). We highlighted distinct molecular mechanisms underlying these regulatory variants, their context-dependent behavior and their utility in interpreting genome-wide associations for 39 chicken complex traits. Finally, our comparative analyses of gene regulation between chickens and mammals demonstrate how this resource can facilitate cross-species gene mapping of complex traits. This study introduces a ChickenGTEx atlas of regulatory variants across 28 tissues and illustrates its utility in deciphering association signals for 39 complex traits in chickens.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 5","pages":"1298-1308"},"PeriodicalIF":31.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798356","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":"Mapping genetic diversity with the GenomeIndia project","authors":"Chandrika Bhattacharyya, Krithika Subramanian, Bharathram Uppili, Nidhan K. Biswas, Shweta Ramdas, Karthik Bharadwaj Tallapaka, Prathima Arvind, Khader Valli Rupanagudi, Arindam Maitra, Tulasi Nagabandi, Tiyasha De, Kuldeep Singh, Praveen Sharma, Nanaocha Sharma, Sunil K. Raghav, Punit Prasad, E. V. Soniya, Abdul Jaleel, Shijulal Nelson Sathi, Madhvi Joshi, Chaitanya Joshi, Mayurika Lahiri, Santosh Dixit, L. S. Shashidhara, Nachimuthu Senthil Kumar, H. Lalhruaitluanga, Lal Nundanga, Venkataram Shivakumar, Ganesan Venkatasubramanian, Naren P. Rao, Mohd Ashraf Ganie, Imtiyaz Ahmad Wani, Ganganath Jha, Ashwin Dalal, Murali Dharan Bashyam, Pritish Kumar Varadwaj, Sanjeev BS, Yogesh Simmhan, Chirag Jain, Durai Sundar, Ishaan Gupta, Pankaj Yadav, Himanshu Sinha, Manikandan Narayanan, Karthik Raman, Raghu Padinjat, Radhakrishnan Sabarinathan, GenomeIndia Consortium, Yadati Narahari, Vijayalakshmi Ravindranath, Thangaraj Kumarasamy, Divya Tej Sowpati, Mohammed Faruq, Analabha Basu, Bratati Kahali","doi":"10.1038/s41588-025-02153-x","DOIUrl":"10.1038/s41588-025-02153-x","url":null,"abstract":"The rich ethnolinguistic and sociocultural differences that exist in India offers a unique opportunity to study human diversity. With the whole genomes of 10,000 healthy and unrelated Indians from 83 populations, the GenomeIndia project captures the genetic diversity of one of the highly underrepresented populations in the global genomics landscape.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 4","pages":"767-773"},"PeriodicalIF":31.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798354","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":"Common-variant and rare-variant genetic architecture of heart failure across the allele-frequency spectrum","authors":"David S. M. Lee, Kathleen M. Cardone, David Y. Zhang, Noah L. Tsao, Sarah Abramowitz, Pranav Sharma, John S. DePaolo, Mitchell Conery, Krishna G. Aragam, Kiran Biddinger, Ozan Dilitikas, Lily Hoffman-Andrews, Renae L. Judy, Atlas Khan, Iftikhar J. Kullo, Megan J. Puckelwartz, Nosheen Reza, Benjamin A. Satterfield, Pankhuri Singhal, Penn Medicine Biobank, Zoltan Arany, Thomas P. Cappola, Eric D. Carruth, Sharlene M. Day, Ron Do, Christopher M. Haggerty, Jacob Joseph, Elizabeth M. McNally, Girish Nadkarni, Anjali T. Owens, Daniel J. Rader, Marylyn D. Ritchie, Yan V. Sun, Benjamin F. Voight, Michael G. Levin, Scott M. Damrauer","doi":"10.1038/s41588-025-02140-2","DOIUrl":"10.1038/s41588-025-02140-2","url":null,"abstract":"Heart failure is a complex trait, influenced by environmental and genetic factors, affecting over 30 million individuals worldwide. Here we report common-variant and rare-variant association studies of all-cause heart failure and examine how different classes of genetic variation impact its heritability. We identify 176 common-variant risk loci at genome-wide significance in 2,358,556 individuals and cluster these signals into five broad modules based on pleiotropic associations with anthropomorphic traits/obesity, blood pressure/renal function, atherosclerosis/lipids, immune activity and arrhythmias. In parallel, we uncover exome-wide significant associations for heart failure and rare predicted loss-of-function variants in TTN, MYBPC3, FLNC and BAG3 using exome sequencing of 376,334 individuals. We find that total burden heritability of rare coding variants is highly concentrated in a small set of Mendelian cardiomyopathy genes, while common-variant heritability is diffusely spread throughout the genome. Finally, we show that common-variant background modifies heart failure risk among carriers of rare pathogenic truncating variants in TTN. Together, these findings discern genetic links between dysregulated metabolism and heart failure and highlight a polygenic component to heart failure not captured by current clinical genetic testing. Common-variant and rare-variant association analyses combining datasets from multiple populations yield insights into the genetic architecture of all-cause heart failure across the allele-frequency spectrum.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 4","pages":"829-838"},"PeriodicalIF":31.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789811","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}