Nature genetics最新文献

{"title":"Purging deleterious mutations through precision genome editing for crop improvement","authors":"","doi":"10.1038/s41588-024-02027-8","DOIUrl":"10.1038/s41588-024-02027-8","url":null,"abstract":"Crop domestication led to the accumulation of mutations that are deleterious for gene function. We predicted the extent of deleterious mutations during the domestication of tomato and applied precision genome editing to correct a floral regulator, resulting in desirable crop attributes, with implications for crop improvement and breeding.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 1","pages":"11-12"},"PeriodicalIF":31.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911693","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 impact of common and rare genetic variants on bradyarrhythmia development","authors":"Lu-Chen Weng, Joel T. Rämö, Sean J. Jurgens, Shaan Khurshid, Mark Chaffin, Amelia Weber Hall, Valerie N. Morrill, Xin Wang, Victor Nauffal, Yan V. Sun, Dominik Beer, Simon Lee, Girish N. Nadkarni, ThuyVy Duong, Biqi Wang, Tomasz Czuba, Thomas R. Austin, Zachary T. Yoneda, Daniel J. Friedman, Anne Clayton, Matthew C. Hyman, Renae L. Judy, Allan C. Skanes, Kate M. Orland, Timothy M. Treu, Matthew T. Oetjens, Alvaro Alonso, Elsayed Z. Soliman, Honghuang Lin, Kathryn L. Lunetta, Jesper van der Pals, Tariq Z. Issa, Navid A. Nafissi, Heidi T. May, Peter Leong-Sit, Carolina Roselli, Seung Hoan Choi, FinnGen, Million Veteran Program, Regeneron Genetics Center, Habib R. Khan, Stacey Knight, Richard Karlsson Linnér, Connie R. Bezzina, Samuli Ripatti, Susan R. Heckbert, J. Michael Gaziano, Ruth J. F. Loos, Bruce M. Psaty, J. Gustav Smith, Emelia J. Benjamin, Dan E. Arking, Daniel J. Rader, Svati H. Shah, Dan M. Roden, Scott M. Damrauer, Lee L. Eckhardt, Jason D. Roberts, Michael J. Cutler, M. Benjamin Shoemaker, Christopher M. Haggerty, Kelly Cho, Aarno Palotie, Peter W. F. Wilson, Patrick T. Ellinor, Steven A. Lubitz","doi":"10.1038/s41588-024-01978-2","DOIUrl":"10.1038/s41588-024-01978-2","url":null,"abstract":"To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively. Four well-known loci (SCN5A/SCN10A, CCDC141, TBX20 and CAMK2D) were shared for SND and DCD, while others were more specific for SND or DCD. SND and DCD showed a moderate genetic correlation (rg = 0.63). Cardiomyocyte-expressed genes were enriched for contributions to DCD heritability. Rare-variant analyses implicated LMNA for all bradyarrhythmia phenotypes, SMAD6 and SCN5A for DCD and TTN, MYBPC3 and SCN5A for PM. These results show that variation in multiple genetic pathways (for example, ion channel function, cardiac developmental programs, sarcomeric structure and cellular homeostasis) appear critical to the development of bradyarrhythmias. Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 1","pages":"53-64"},"PeriodicalIF":31.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-01978-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911643","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":"Multi-omic profiling highlights factors associated with resistance to immuno-chemotherapy in non-small-cell lung cancer","authors":"Yilv Yan, Dongqing Sun, Junjie Hu, Yue Chen, Liangdong Sun, Huansha Yu, Yicheng Xiong, Zhida Huang, Haoran Xia, Xinsheng Zhu, Dongliang Bian, Fenghuan Sun, Likun Hou, Chunyan Wu, Orion R. Fan, Haiyang Hu, An Zeng, Lele Zhang, Yi Eve Sun, Chenfei Wang, Peng Zhang","doi":"10.1038/s41588-024-01998-y","DOIUrl":"10.1038/s41588-024-01998-y","url":null,"abstract":"Although immune checkpoint blockade (ICB) therapies have shifted the treatment paradigm for non-small-cell lung cancer (NSCLC), many patients remain resistant. Here we characterize the tumor cell states and spatial cellular compositions of the NSCLC tumor microenvironment (TME) by analyzing single-cell transcriptomes of 232,080 cells and spatially resolved transcriptomes of tumors from 19 patients before and after ICB–chemotherapy. We find that tumor cells and secreted phosphoprotein 1-positive macrophages interact with collagen type XI alpha 1 chain-positive cancer-associated fibroblasts to stimulate the deposition and entanglement of collagen fibers at tumor boundaries, obstructing T cell infiltration and leading to poor prognosis. We also reveal distinct states of tertiary lymphoid structures (TLSs) in the TME. Activated TLSs are associated with improved prognosis, whereas a hypoxic microenvironment appears to suppress TLS development and is associated with poor prognosis. Our study provides novel insights into different cellular and molecular components corresponding to NSCLC ICB–chemotherapeutic responsiveness, which will benefit future individualized immuno-chemotherapy. Samples from 19 patients with non-small-cell lung cancer treated with a combination of chemotherapy and immune checkpoint blockade are profiled with single-cell RNA sequencing and spatial transcriptomics to identify factors associated with treatment resistance.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 1","pages":"126-139"},"PeriodicalIF":31.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797061","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":"Spatial biology captures the effects of neoadjuvant chemo-immunotherapy in lung cancer","authors":"Jonathan H. Chen, Justin F. Gainor","doi":"10.1038/s41588-024-01992-4","DOIUrl":"10.1038/s41588-024-01992-4","url":null,"abstract":"PD-1 pathway blockade in combination with chemotherapy has emerged as a treatment paradigm for patients with resectable lung cancer, but insights into predictive biomarkers and mechanisms of immune responses are lacking. A study uses spatial transcriptomic methods to identify patterns within the tumor microenvironment associated with response.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 1","pages":"6-8"},"PeriodicalIF":31.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796908","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":"Chromatin topology dynamics in gene activation","authors":"Petra Gross","doi":"10.1038/s41588-024-02041-w","DOIUrl":"10.1038/s41588-024-02041-w","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2589-2589"},"PeriodicalIF":31.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797064","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":"Functional genomics of height heritability","authors":"Tiago Faial","doi":"10.1038/s41588-024-02043-8","DOIUrl":"10.1038/s41588-024-02043-8","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2589-2589"},"PeriodicalIF":31.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797271","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":"DRAGEN optimizes genomic variant detection","authors":"Wei Li","doi":"10.1038/s41588-024-02042-9","DOIUrl":"10.1038/s41588-024-02042-9","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2589-2589"},"PeriodicalIF":31.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797062","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":"Improved tool for scRNA-seq analysis","authors":"Michael Fletcher","doi":"10.1038/s41588-024-02040-x","DOIUrl":"10.1038/s41588-024-02040-x","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2589-2589"},"PeriodicalIF":31.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797063","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":"Genetic control of alternative splicing across blood cell types from diverse Asian donors","authors":"","doi":"10.1038/s41588-024-02020-1","DOIUrl":"10.1038/s41588-024-02020-1","url":null,"abstract":"Existing functional genomics datasets are European-centric. The Asian Immune Diversity Atlas incorporated single-cell RNA-sequencing data from approximately 1 million peripheral blood mononuclear cells from around 500 donors of diverse Asian ancestries. Mapping of splicing quantitative trait loci revealed context-specific regulation of alternative splicing, as well as cell-type and ancestry-specific genetic effects on complex diseases.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2602-2603"},"PeriodicalIF":31.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763210","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":"Publisher Correction: Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience","authors":"Sean J. Jurgens, Joel T. Rämö, Daria R. Kramarenko, Leonoor F. J. M. Wijdeveld, Jan Haas, Mark D. Chaffin, Sophie Garnier, Liam Gaziano, Lu-Chen Weng, Alex Lipov, Sean L. Zheng, Albert Henry, Jennifer E. Huffman, Saketh Challa, Frank Rühle, Carmen Diaz Verdugo, Christian Krijger Juárez, Shinwan Kany, Constance A. van Orsouw, Kiran Biddinger, Edwin Poel, Amanda L. Elliott, Xin Wang, Catherine Francis, Richard Ruan, Satoshi Koyama, Leander Beekman, Dominic S. Zimmerman, Jean-François Deleuze, Eric Villard, David-Alexandre Trégouët, Richard Isnard, FinnGen, VA Million Veteran Program, HERMES Consortium, Dorret I. Boomsma, Eco J. C. de Geus, Rafik Tadros, Yigal M. Pinto, Arthur A. M. Wilde, Jouke-Jan Hottenga, Juha Sinisalo, Teemu Niiranen, Roddy Walsh, Amand F. Schmidt, Seung Hoan Choi, Kyong-Mi Chang, Philip S. Tsao, Paul M. Matthews, James S. Ware, R. Thomas Lumbers, Saskia van der Crabben, Jari Laukkanen, Aarno Palotie, Ahmad S. Amin, Philippe Charron, Benjamin Meder, Patrick T. Ellinor, Mark Daly, Krishna G. Aragam, Connie R. Bezzina","doi":"10.1038/s41588-024-02047-4","DOIUrl":"10.1038/s41588-024-02047-4","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2843-2843"},"PeriodicalIF":31.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-02047-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776908","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}