Nature genetics最新文献

{"title":"Cell-state-specific enhancer design in hematopoiesis","authors":"Petra Gross","doi":"10.1038/s41588-025-02241-y","DOIUrl":"10.1038/s41588-025-02241-y","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1325-1325"},"PeriodicalIF":31.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269046","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 maize cis-regulatory landscape","authors":"Tiago Faial","doi":"10.1038/s41588-025-02244-9","DOIUrl":"10.1038/s41588-025-02244-9","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1325-1325"},"PeriodicalIF":31.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269049","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":"Mendel’s pea traits pinned down","authors":"Kyle Vogan","doi":"10.1038/s41588-025-02242-x","DOIUrl":"10.1038/s41588-025-02242-x","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1325-1325"},"PeriodicalIF":31.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269050","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 map of blood regulatory variation in South Africans enables GWAS interpretation","authors":"Stephane E. Castel, Furahini D. Tluway, Anne-Katrin Emde, Natalie Smyth, Mohd Karim, Dhriti Sengupta, Olivia A. Gray, Melissa Hendershott, Sarah LeBaron von Baeyer, Erin E. Burke, Sarah Kaewert, Khanh-Dung H. Nguyen, Solomon S. R. Choma, Reneilwe G. Mashaba, Lisa K. Micklesfield, Chodziwadziwa Kabudula, Kathleen Kahn, F. Xavier Gomez-Olive, Stephen Tollman, Ananyo Choudhury, Phelelani T. Mpangase, Scott Hazelhurst, Kaja A. Wasik, Laura Yerges-Armstrong, Michèle Ramsay","doi":"10.1038/s41588-025-02223-0","DOIUrl":"https://doi.org/10.1038/s41588-025-02223-0","url":null,"abstract":"<p>Functional genomics resources are critical for interpreting human genetic studies, but currently they are predominantly from European-ancestry individuals. Here we present the South African Blood Regulatory (SABR) resource, a map of blood regulatory variation that includes three South Eastern Bantu-speaking groups. Using paired whole-genome and blood transcriptome data from over 600 individuals, we map the genetic architecture of 40 blood cell traits derived from deconvolution analysis, as well as expression, splice and cell-type interaction quantitative trait loci. We comprehensively compare SABR to the Genotype Tissue Expression Project and characterize thousands of regulatory variants only observed in African-ancestry individuals. Finally, we demonstrate the increased utility of SABR for interpreting African-ancestry association studies by identifying putatively causal genes and molecular mechanisms through colocalization analysis of blood-relevant traits from the Pan-UK Biobank. Importantly, we make full SABR summary statistics publicly available to support the African genomics community.</p>","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"103 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260417","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":"Author Correction: The genomic landscape of gene-level structural variations in Japanese and global soybean Glycine max cultivars","authors":"Ryoichi Yano, Feng Li, Susumu Hiraga, Ryoma Takeshima, Michie Kobayashi, Kyoko Toda, Yosuke Umehara, Hiromi Kajiya-Kanegae, Hiroyoshi Iwata, Akito Kaga, Masao Ishimoto","doi":"10.1038/s41588-025-02256-5","DOIUrl":"https://doi.org/10.1038/s41588-025-02256-5","url":null,"abstract":"<p>Correction to: <i>Nature Genetics</i> https://doi.org/10.1038/s41588-025-02113-5, published online 3 March 2025.</p>","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"40 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252304","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":"Coordinated function of paired NLRs confers Yr84-mediated stripe rust resistance in wheat","authors":"Valentyna Klymiuk,&nbsp;Krystalee Wiebe,&nbsp;Harmeet Singh Chawla,&nbsp;Jennifer Ens,&nbsp;Rajagopal Subramaniam,&nbsp;Curtis J. Pozniak","doi":"10.1038/s41588-025-02203-4","DOIUrl":"10.1038/s41588-025-02203-4","url":null,"abstract":"Cloning of resistance genes expands our understanding of their function and facilitates their deployment in breeding. Here we report the cloning of two genes from wild emmer wheat (Triticum turgidum ssp. dicoccoides) underlying Yr84-mediated stripe rust resistance using a combination of fine mapping, long-read sequencing and mutation-induced functional validation. In contrast to all previously cloned stripe rust genes, the incompletely dominant Yr84 phenotype is conferred through the coordinated function of paired nucleotide-binding leucine-rich repeat (NLR) genes CNL and NL. We reason that based on their genomic organization, annotation, expression profiles and predicted protein structure, CNL functions as a sensor NLR, responsible for effector recognition, and NL acts as a helper NLR, initiating downstream resistance cascades. Both the CNL and NL lack an integrated domain(s) previously implicated in effector recognition by paired NLRs; therefore, these findings contribute insights into the structure and molecular mechanisms of the function of plant paired NLRs. The study reports the cloning of paired NLR genes CNL and NL from wild emmer wheat and demonstrates their coordinated function in conferring Yr84-mediated wheat stripe rust resistance.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1535-1542"},"PeriodicalIF":31.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237779","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":"Author Correction: Comprehensive molecular profiling of multiple myeloma identifies refined copy number and expression subtypes","authors":"Sheri Skerget, Daniel Penaherrera, Ajai Chari, Sundar Jagannath, David S. Siegel, Ravi Vij, Gregory Orloff, Andrzej Jakubowiak, Ruben Niesvizky, Darla Liles, Jesus Berdeja, Moshe Levy, Jeffrey Wolf, Saad Z. Usmani, Austin W. Christofferson, Sara Nasser, Jessica L. Aldrich, Christophe Legendre, Brooks Benard, Chase Miller, Bryce Turner, Ahmet Kurdoglu, Megan Washington, Venkata Yellapantula, Jonathan R. Adkins, Lori Cuyugan, Martin Boateng, Adrienne Helland, Shari Kyman, Jackie McDonald, Rebecca Reiman, Kristi Stephenson, Erica Tassone, Alex Blanski, Brianne Livermore, Meghan Kirchhoff, Daniel C. Rohrer, Mattia D’Agostino, Manuela Gambella, Kimberly Collison, Jennifer Stumph, Pam Kidd, Andrea Donnelly, Barbara Zaugg, Maureen Toone, Kyle McBride, Mary DeRome, Jennifer Rogers, David Craig, Winnie S. Liang, Norma C. Gutierrez, Scott D. Jewell, John Carpten, Kenneth C. Anderson, Hearn Jay Cho, Daniel Auclair, Sagar Lonial, Jonathan J. Keats","doi":"10.1038/s41588-025-02251-w","DOIUrl":"https://doi.org/10.1038/s41588-025-02251-w","url":null,"abstract":"<p>Correction to: <i>Nature Genetics</i> https://doi.org/10.1038/s41588-024-01853-0, published online 19 August 2024.</p>","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"1 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237999","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":"Chromothripsis-associated chromosome 21 amplification orchestrates transformation to blast-phase MPN through targetable overexpression of DYRK1A","authors":"Charlotte K. Brierley,&nbsp;Bon Ham Yip,&nbsp;Giulia Orlando,&nbsp;Jeremy Wen,&nbsp;Sean Wen,&nbsp;Harsh Goyal,&nbsp;Max Levine,&nbsp;G. Maria Jakobsdottir,&nbsp;Avraam Tapinos,&nbsp;Alex J. Cornish,&nbsp;Antonio Rodriguez-Romera,&nbsp;Alba Rodriguez-Meira,&nbsp;Matthew Bashton,&nbsp;Angela Hamblin,&nbsp;Sally Ann Clark,&nbsp;Joseph C. Hamley,&nbsp;Olivia Fox,&nbsp;Madalina Giurgiu,&nbsp;Jennifer O’Sullivan,&nbsp;Lauren Murphy,&nbsp;Assunta Adamo,&nbsp;Aude Anais Olijnik,&nbsp;Anitria Cotton,&nbsp;Emily Hendrix,&nbsp;Shilpa Narina,&nbsp;Shondra M. Pruett-Miller,&nbsp;Amir Enshaei,&nbsp;Claire Harrison,&nbsp;Mark Drummond,&nbsp;Steven Knapper,&nbsp;Ayalew Tefferi,&nbsp;Iléana Antony-Debré,&nbsp;James Davies,&nbsp;Anton G. Henssen,&nbsp;Supat Thongjuea,&nbsp;David C. Wedge,&nbsp;Stefan N. Constantinescu,&nbsp;Elli Papaemmanuil,&nbsp;Bethan Psaila,&nbsp;John D. Crispino,&nbsp;Adam J. Mead","doi":"10.1038/s41588-025-02190-6","DOIUrl":"10.1038/s41588-025-02190-6","url":null,"abstract":"Chromothripsis, the chaotic shattering and repair of chromosomes, is common in cancer. Whether chromothripsis generates actionable therapeutic targets remains an open question. In a cohort of 64 patients in blast phase of a myeloproliferative neoplasm (BP-MPN), we describe recurrent amplification of a region of chromosome 21q (‘chr. 21amp’) in 25%, driven by chromothripsis in a third of these cases. We report that chr. 21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. DYRK1A, a serine threonine kinase, is the only gene in the 2.7-megabase minimally amplified region that showed both increased expression and chromatin accessibility compared with non-chr. 21amp BP-MPN controls. DYRK1A is a central node at the nexus of multiple cellular functions critical for BP-MPN development and is essential for BP-MPN cell proliferation in vitro and in vivo, and represents a druggable axis. Collectively, these findings define chr. 21amp as a prognostic biomarker in BP-MPN, and link chromothripsis to a therapeutic target. Multiomic analysis of blast-phase myeloproliferative neoplasms identifies a chromosome 21 amplicon harboring DYRK1A as a clonal and therapeutically targetable event in around a quarter of cases.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1478-1492"},"PeriodicalIF":31.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-025-02190-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237782","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 modifiers of somatic expansion and clinical phenotypes in Huntington’s disease highlight shared and tissue-specific effects","authors":"Genetic Modifiers of Huntington’s Disease (GeM-HD) Consortium","doi":"10.1038/s41588-025-02191-5","DOIUrl":"10.1038/s41588-025-02191-5","url":null,"abstract":"An inherited, expanded CAG repeat in HTT undergoes further somatic expansion to cause Huntington’s disease (HD). To gain insights into this molecular mechanism, we compared genome-wide association studies of somatic expansion in blood and somatic expansion-driven HD clinical phenotypes. Here, we show that somatic expansion is driven by a mismatch repair-related process whose genetic modification and consequences show unexpected complexity, including cell-type specificity. The HD clinical trajectory is further modified by non-DNA repair genes that differentially influence measures of cognitive and motor dysfunction. In addition to shared (DNA repair genes MSH3, PMS2 and FAN1) and distinct trans-modifiers, a synonymous CAG-adjacent variant in HTT dramatically hastens motor onset without increasing somatic expansion, while a cis-acting 5′-untranslated region variant promotes blood repeat expansion without influencing clinical HD. Our findings are directly relevant to the therapeutic suppression of expansion in DNA repeat disorders and provide additional clues to HD pathogenic mechanisms beyond somatic expansion. Comparison of genome-wide association studies of HTT CAG repeat expansion in blood to expansion-driven clinical traits in Huntington’s disease identifies shared and distinct modifiers implicating DNA mismatch repair with tissue and cell-type specificity.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1426-1436"},"PeriodicalIF":31.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144238000","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 head-to-head NLR gene pair from wild emmer confers stripe rust resistance in wheat","authors":"Yanling Hu,&nbsp;Miaomiao Li,&nbsp;Yuqin Li,&nbsp;Lilin Du,&nbsp;Ruijie Xie,&nbsp;Fei Ni,&nbsp;Chongjing Xia,&nbsp;Ke Wang,&nbsp;Yanyan Huang,&nbsp;Binyang Xu,&nbsp;Yinghui Li,&nbsp;Yunfeng Jiang,&nbsp;Ming Hao,&nbsp;Bo Jiang,&nbsp;Shunzong Ning,&nbsp;Zhongwei Yuan,&nbsp;Lihua Feng,&nbsp;Lianquan Zhang,&nbsp;Shisheng Chen,&nbsp;Bihua Wu,&nbsp;Zhiyong Liu,&nbsp;Tzion Fahima,&nbsp;Dengcai Liu,&nbsp;Lin Huang","doi":"10.1038/s41588-025-02207-0","DOIUrl":"10.1038/s41588-025-02207-0","url":null,"abstract":"Wheat stripe rust poses a major threat to global food security. Discovery of disease resistance genes from wild relatives enables multigene stacking that could enhance durability. Here we use map-based cloning and long-read sequencing to isolate two adjacent nucleotide-binding and leucine-rich repeat (NLR) receptors from wild emmer wheat. Using mutagenesis, gene silencing and genetic transformation, we show that the genes TdNLR1 and TdNLR2 oriented head-to-head are both required for YrTD121-mediated stripe rust resistance. TdNLR1 encodes a canonical NLR (CC-NB-ARC-LRR) protein, whereas TdNLR2 encodes an atypical one (NB-ARC-LRR). Both genes lack an integrated domain previously associated with effector perception, representing an uncommon architecture for paired NLRs in plants. The coiled coil domain of TdNLR1 triggers cell death and self-associates in planta. YrTD121 was present in wild emmer but absent in all other Triticum species examined. Our work sheds light on the function of paired NLRs in conferring disease resistance and facilitates breeding for resistance. Two genetically linked TdNLR genes from wild emmer wheat are both required for YrTD121-mediated stripe rust resistance. The TdNLR1 and TdNLR2 pair lacks an integrated domain, representing an uncommon architecture for paired NLRs in plants.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1543-1552"},"PeriodicalIF":31.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237781","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}