Nature genetics最新文献

{"title":"A catalog of LINE-1 insertions","authors":"Petra Gross","doi":"10.1038/s41588-026-02559-1","DOIUrl":"10.1038/s41588-026-02559-1","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"472-472"},"PeriodicalIF":29.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147441953","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 genetic module boosts grain yield and nitrogen use efficiency by improving nitrate transport in maize","authors":"Meiling Zhang, Ziqi Wu, Liangliang Huang, Xiaomeng Shen, Kangqi Wang, Yingying Hu, Burebiyanmu Wubulikasimu, Yizhou Qin, Junzheng Fu, Ziwei Luo, Bo Yang, Xiaoming Zhao, Xiqing Wang, Feng Qin, Chao Bian, Haiming Zhao, Jian Chen, Weibin Song, Yi Wang, Jinsheng Lai","doi":"10.1038/s41588-026-02532-y","DOIUrl":"10.1038/s41588-026-02532-y","url":null,"abstract":"Although nitrogen fertilizer use has boosted crop yields, excessive application diminishes crop nitrogen use efficiency (NUE) and causes environmental problems. Therefore, increasing crop NUE is urgently needed for agricultural sustainability. Through a genome-wide association study, we identified a locus, NCR1 (Nitrate Concentration Regulator 1), that correlates with nitrate concentrations in maize root xylem. NCR1 encodes a MYB transcription factor that positively regulates the transcription of nitrate transporter NRT2.3 expressed predominantly in root xylem parenchyma cells. The NCR1–NRT2.3 transcription module responds to external nitrogen and controls nitrate translocation from roots to shoots. The superior NCR1−In allele with a 123-bp promoter deletion has decreased in frequency as nitrogen fertilizer use in China has increased. Overexpression of NCR1 or NRT2.3, or introgression of NCR1−In, increases grain yield and nitrogen content in the shoot and seed. This study uncovers a crucial genetic module for improving grain yield and NUE in maize. NCR1 (nitrate concentration regulator 1) promotes root-to-shoot nitrate transport by regulating the transcription of nitrate transporter NRT2.3, thereby contributing to grain yield in maize.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"618-629"},"PeriodicalIF":29.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147441951","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":"Generalists connect microbiomes","authors":"Hui Hua","doi":"10.1038/s41588-026-02560-8","DOIUrl":"10.1038/s41588-026-02560-8","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"472-472"},"PeriodicalIF":29.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147441952","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 repeat expansion in GOLGA8A is a major risk factor for atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions","authors":"Wouter De Coster, Marleen Van den Broeck, Matt Baker, Nikhil B. Ghayal, Sarah Wynants, Anthony Batzler, Cyril Pottier, Sara Alidadiani, Fahri Küçükali, Gregory D. Jenkins, Rafaela Policarpo, Marka van Blitterswijk, Mariely DeJesus-Hernandez, Alexandra I. Soto-Beasley, Júlia Faura, Elise Coopman, Saskia Hutten, Merel O. Mol, David Wallon, Anne Sieben, Elizabeth C. Finger, Melissa E. Murray, Shelley L. Forrest, Maria C. Tartaglia, Claire Troakes, Jeroen G. J. van Rooij, Aivi T. Nguyen, R. Ross Reichard, Natalie L. Woodman, Alissa L. Nana, Sandra Weintraub, Tamar Gefen, Bart De Vil, Istvan Bodi, Oscar L. Lopez, Susana Boluda, Serge Belliard, Florence Lebert, Florent Marguet, Qinwen Mao, Marsel M. Mesulam, Adam L. Boxer, Mathieu Vandenbulcke, EunRan Suh, Jolien Schaeverbeke, Jean-Charles Lambert, Sonja W. Scholz, Clifton L. Dalgard, Bryan J. Traynor, Raphael J. Gibbs, Gerard D. Schellenberg, Dorothee Dormann, Geert Joris, Tim De Pooter, Peter De Rijk, Svenn D’Hert, Jasper Van Dongen, Julie van der Zee, Mojca Strazisar, Marla Gearing, Thomas Kukar, Margaret Flanagan, Sebastiaan Engelborghs, Bernardino Ghetti, Kathy L. Newell, Andrew King, Sigrun Roeber, Howard J. Rosen, Salvatore Spina, Patrick Cras, Nilüfer Ertekin-Taner, Zbigniew K. Wszolek, Ryan J. Uitti, William P. Cheshire, Wolfgang Singer, Jochen Herms, Keith A. Josephs, Jennifer L. Whitwell, Ronald C. Petersen, Florence Pasquier, Gaël Nicolas, Rudolph Castellani, Jonathan Glass, Bruce L. Miller, Gabor G. Kovacs, Robert A. Rissman, Annie Hiniker, Vincent Deramecourt, Lee-Cyn Ang, Jin Lee-Way, Vivianna M. Van Deerlin, Brittany N. Dugger, Dietmar R. Thal, Lea T. Grinberg, Carlos Cruchaga, Thomas Arzberger, David G. Munoz, Julia Keith, Lorne Zinman, Ekaterina Rogaeva, Edward B. Lee, Stephen J. Haggarty, Olaf Ansorge, Masud Husain, Glenda M. Halliday, Safa Al-Sarraj, Owen A. Ross, Kristel Sleegers, Rik Vandenberghe, Bradley F. Boeve, Neill R. Graff-Radford, Julia Kofler, Charles L. White III, Tammaryn Lashley, Manuela Neumann, Joanna M. Biernacka, William W. Seeley, Harro Seelaar, John C. van Swieten, Jonathan D. Rohrer, Dennis W. Dickson, Ian R. A. Mackenzie, Rosa Rademakers","doi":"10.1038/s41588-026-02537-7","DOIUrl":"10.1038/s41588-026-02537-7","url":null,"abstract":"Atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions (aFTLD-U) is neuropathologically characterized by aggregation of the FET family of proteins and clinically manifests as sporadic young-onset frontotemporal dementia. Here we describe a major risk locus on chr15q14 identified through a genome-wide association study in 59 pathologically confirmed aFTLD-U cases and 3,153 controls (lead single nucleotide polymorphism rs549846383, P = 5.85 × 10−21, odds ratio 26.7). When combined with data from 28 additional aFTLD-U cases, 3,712 controls and 3,215 individuals with other neurodegenerative diseases and by leveraging in-house and public long-read genome sequencing data from 1,715 individuals, we identified a tandem repeat expansion on the associated haplotypes in an intron of GOLGA8A. We found variation in repeat length, motif length, and motif sequence, with long CT-dimer expansions strongly associated with aFTLD-U. Although the functional consequence of this repeat remains unknown, its presence in nearly 60% of aFTLD-U cases points to a fundamental role in disease pathogenesis. Genome-wide analysis coupled with long-read sequencing identifies a repeat expansion in GOLGA8A associated with high risk for atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 4","pages":"726-736"},"PeriodicalIF":29.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-026-02537-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147394047","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":"CDK4/6 inhibition mitigates chemotherapy-induced expansion of TP53-mutant clonal hematopoiesis","authors":"Irenaeus C. C. Chan, Pu Zhang, Xiangyu Pan, Cynthia Castro, Nina Fox, Alexander M. Lewis, Kenyon Weis, Adriana Cuibus, Steven Tittley, Giulia Petrone, J. Scott Beeler, Duc Tran, Griffen Mustion, Catrina Fronick, Konrad H. Stopsack, Carlos Cruchaga, Omar Abdel-Wahab, Kelly L. Bolton","doi":"10.1038/s41588-026-02526-w","DOIUrl":"10.1038/s41588-026-02526-w","url":null,"abstract":"Therapy-related myeloid neoplasm (tMN) is a fatal consequence of exposure to cytotoxic therapy administered in the treatment of cancer. Individuals with pre-existing TP53 clonal hematopoiesis (CH) are at high risk of tMN, with avoidance of therapy being the only strategy to reduce tMN risk. Here, in four randomized clinical trials, we show that the CDK4/6 inhibitor trilaciclib, given in conjunction with a variety of chemotherapeutic regimens and across diverse populations of patients with cancer, mitigates chemotherapy-related expansion of CH clones with mutations in DNA damage response genes, including TP53. This finding was also observed in a syngeneic mouse model of TP53-mutant CH, demonstrating that CDK4/6 inhibition blocks platinum-induced TP53 competitive repopulation through promoting hematopoietic stem and progenitor quiescence and decreasing the stemness advantage of TP53-mutant clones. This represents a proof of concept for a potential pharmacologic strategy to block chemotherapy-induced expansion of preleukemic TP53-mutant clones. Analysis of clinical trial data suggests that CDK4/6 inhibitors prevent the expansion of TP53-mutant clones in the blood, potentially mitigating the risk of secondary myeloid neoplasms in patients treated with cytotoxic drugs.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"582-592"},"PeriodicalIF":29.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-026-02526-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393748","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":"Curbing the risk of therapy-related myeloid neoplasms","authors":"","doi":"10.1038/s41588-026-02525-x","DOIUrl":"10.1038/s41588-026-02525-x","url":null,"abstract":"The development of therapy-related myeloid neoplasms is a dangerous complication of cancer-directed therapy and is driven by the selection of hematopoietic cells with mutations in genes involved in the DNA damage response pathway. We show that short-term CDK4/6 inhibition mitigates clonal expansion of TP53-mutant hematopoietic cells during cytotoxic chemotherapy.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"477-478"},"PeriodicalIF":29.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393749","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":"Transcriptional interference revisited.","authors":"Martin Fischer, Steve Hoffmann","doi":"10.1038/s41588-026-02536-8","DOIUrl":"https://doi.org/10.1038/s41588-026-02536-8","url":null,"abstract":"<p><p>The transcriptional interference model suggests that RNA polymerases elongating through overlapping transcription units mutually inhibit transcription and disrupt associated cis-regulatory elements. As a longstanding fundamental concept of gene regulation, the idea of reciprocal inhibition between sense and antisense transcription has been supported by a significant body of research. However, despite the model's biophysical plausibility and historical significance, evidence from large-scale transcriptome studies raises questions about its universal applicability. In particular, the new data indicate that a measurable influence of transcriptional interference is absent from the majority of loci with overlapping transcription. Here we highlight key aspects of overlapping transcription and propose potential solutions to this emerging puzzle. Gaining a better understanding of the molecular mechanisms that render loci sensitive or resistant to interference could lead to groundbreaking insights into the biology of gene regulation.</p>","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":" ","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434389","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":"Population-level structural variant characterization using pangenome graphs","authors":"Songbo Wang,&nbsp;Tun Xu,&nbsp;Pengyu Zhang,&nbsp;Kai Ye","doi":"10.1038/s41588-026-02538-6","DOIUrl":"10.1038/s41588-026-02538-6","url":null,"abstract":"Population-level structural variant (SV) profiling is crucial in the era of pangenomes. However, identifying SVs from genome assemblies and pangenome graphs remains a substantial challenge. Here we present Swave, a sequence-to-image, deep learning-based method that accurately resolves both simple and complex SVs, along with their population characteristics, from assembly-derived pangenome graphs. Swave introduces ‘projection waves’ to summarize the dotplot images that capture mapping patterns between reference and SV-indicating alleles in the pangenome. Then, a recurrent neural network distinguishes true SV signals from background noise introduced by genomic repeats. Swave demonstrates superior performance in both SV-type classification and genotyping compared with existing methods. When applied to healthy cohorts and rare-disease cohorts, Swave reveals complex and polymorphic SV patterns across human populations and identifies potentially pathogenic SVs. These advancements will facilitate the creation of comprehensive population-level SV catalogs, deepening our understanding of SVs in genetic diversity and disease associations. Swave is a method to call structural variants from pangenome graphs using a recurrent neural network to identify structural variant patterns, including complex structural variants.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"664-672"},"PeriodicalIF":29.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381753","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":"Allelic variation at a single locus distinguishes spring and winter faba beans","authors":"Hailin Zhang,&nbsp;Alex Windhorst,&nbsp;Elesandro Bornhofen,&nbsp;Zuzana Tulpova,&nbsp;Petr Novak,&nbsp;Jiri Macas,&nbsp;Hana Simkova,&nbsp;Marcin Nadzieja,&nbsp;Jung Min Kim,&nbsp;Dustin Cram,&nbsp;Yongguo Cao,&nbsp;David J. F. Konkin,&nbsp;Olaf Sass,&nbsp;Gregor Welna,&nbsp;Axel Himmelbach,&nbsp;Martin Mascher,&nbsp;Wolfgang Link,&nbsp;Soon-Jae Kwon,&nbsp;Tae-Jin Yang,&nbsp;Stig Uggerhøj Andersen,&nbsp;Murukarthick Jayakodi","doi":"10.1038/s41588-026-02524-y","DOIUrl":"10.1038/s41588-026-02524-y","url":null,"abstract":"Winter faba beans exhibit significant yield advantages over spring cultivars and hold promise for enhancing local protein production and agricultural sustainability. However, the threat of winter kill limits wider cultivation, and the genetics of faba bean winter hardiness remain unresolved. Here we develop a greatly improved faba bean reference genome and combine this with resequencing and phenotyping of winter and spring accessions to identify genetic determinants of winter hardiness. Genome-wide association analysis of frost tolerance traits identifies a major winter hardiness locus, the most strongly associated variant of which explains the vast majority of phenotypic variation and accurately differentiates between winter and spring types. Furthermore, we identify additional signals within the winter faba bean gene pool that could lead to further improvement of winter hardiness. Our work provides improved genomic resources and resolves the genetics of a key agronomic trait in a global protein crop to facilitate future breeding efforts. An improved faba bean reference genome and resequencing of winter and spring faba bean accessions identify genetic determinants of winter hardiness.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"655-663"},"PeriodicalIF":29.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-026-02524-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381751","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":"The emerging role of kinase fusion proteins in cereal immunity","authors":"Oliver R. Powell,&nbsp;Francisco J. Guzmán-Vega,&nbsp;Daniel S. Yu,&nbsp;Yan L. Wang,&nbsp;Ping Lu,&nbsp;Stefan T. Arold,&nbsp;Zhiyong Liu,&nbsp;Mark J. Banfield,&nbsp;Brande B. H. Wulff,&nbsp;Renjie Chen","doi":"10.1038/s41588-026-02515-z","DOIUrl":"10.1038/s41588-026-02515-z","url":null,"abstract":"Kinase fusion proteins (KFPs) are an emerging class of diverse intracellular plant immune receptors with critical roles in immunity in wheat (Triticum aestivum) and other members of the Triticeae. These proteins contain at least one kinase domain fused to one or more additional domains, possibly including another kinase domain. Many KFP kinase domains are predicted to possess an atypical structural motif, the extended β-finger, indicating that KFPs may operate through shared mechanisms in plant immunity despite their structural diversity. Recent research has demonstrated that KFP SR62TK from Aegilops sharonensis and RWT4 (allelic to PM24) from wheat serve as primary receptors that initiate immune signaling by recruiting a nucleotide-binding leucine-rich repeat (NLR) protein similar to sensor and helper NLR pairs. This study consolidates the current understanding of KFPs, emphasizing their structural and functional diversity, evolutionary significance and potential for engineering durable disease resistance in crops. This study explores kinase fusion proteins, a recently described class of plant immune receptors, focusing on emerging evidence that they function as sophisticated sensors and highlighting their potential for engineering broad-spectrum disease resistance in cereals.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 4","pages":"695-703"},"PeriodicalIF":29.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346268","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}