Nature genetics最新文献_第8页

Harnessing genomics for early cancer detection, risk stratification and prevention 利用基因组学进行早期癌症检测、风险分层和预防。

IF 29 1区生物学

Nature genetics Pub Date : 2026-03-02 DOI: 10.1038/s41588-026-02505-1

Muxin Gu, Woody Z. Zhang, Rebecca C. Fitzgerald, Alexander M. Frankell, George S. Vassiliou

{"title":"Harnessing genomics for early cancer detection, risk stratification and prevention","authors":"Muxin Gu, Woody Z. Zhang, Rebecca C. Fitzgerald, Alexander M. Frankell, George S. Vassiliou","doi":"10.1038/s41588-026-02505-1","DOIUrl":"10.1038/s41588-026-02505-1","url":null,"abstract":"Therapeutic advances have improved cancer outcomes, but early-stage detection remains the single most important determinant of favorable prognoses across many cancer types. Cancer genomics has yielded detailed maps of somatic mutation and methylation patterns characteristic of different cancers, enabling the development of assays to detect mutation-bearing tumor-derived DNA in tissue biopsies, blood and other body fluids at the earliest stages of disease. In parallel, it has also become clear that small clones bearing cancer-associated mutations arise commonly in histologically normal tissues, a phenomenon that becomes universal in proliferative tissues with age but leads to cancer in only a small minority of individuals. This review article outlines established strategies for early cancer detection and highlights emerging insights into the genetics of precancerous mutant clones that have led to the recent development of prognostic frameworks for identifying high-risk individuals, making it increasingly possible to intercept evolving cancer at a premalignant or early malignant stage, when interventions are most effective. This Review outlines how recent advances in cancer genetics and genomics are driving progress in early cancer detection and facilitating the identification of individuals with high-risk precancerous lesions.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 4","pages":"704-716"},"PeriodicalIF":29.0,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329216","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}

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Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk 自身免疫性甲状腺功能减退症的全基因组关联分析揭示了自身免疫性和甲状腺特异性的贡献，并与癌症风险呈负相关。

IF 29 1区生物学

Nature genetics Pub Date : 2026-02-26 DOI: 10.1038/s41588-026-02521-1

Mary Pat Reeve, Masahiro Kanai, Daniel B. Graham, Juha Karjalainen, Shuang Luo, Nikita Kolosov, Cameron Adams, Jarmo Ritari, Konrad J. Karczewski, Tuomo Kiiskinen, Yu Jiang, Zachary Fuller, Juha Mehtonen, Mitja I. Kurki, Zia Khan, FinnGen, Jukka Partanen, Mark I. McCarthy, Mykyta Artomov, Aarno Palotie, Tiinamaija Tuomi, Matti Pirinen, Jukka Kero, Ramnik J. Xavier, Mark J. Daly, Samuli Ripatti

{"title":"Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk","authors":"Mary Pat Reeve, Masahiro Kanai, Daniel B. Graham, Juha Karjalainen, Shuang Luo, Nikita Kolosov, Cameron Adams, Jarmo Ritari, Konrad J. Karczewski, Tuomo Kiiskinen, Yu Jiang, Zachary Fuller, Juha Mehtonen, Mitja I. Kurki, Zia Khan, FinnGen, Jukka Partanen, Mark I. McCarthy, Mykyta Artomov, Aarno Palotie, Tiinamaija Tuomi, Matti Pirinen, Jukka Kero, Ramnik J. Xavier, Mark J. Daly, Samuli Ripatti","doi":"10.1038/s41588-026-02521-1","DOIUrl":"10.1038/s41588-026-02521-1","url":null,"abstract":"The high prevalence (>5%) of autoimmune hypothyroidism (AIHT) provides a unique opportunity to dissect genetic contributions to systemic and organ-specific autoimmunity. Here we performed a genome-wide association meta-analysis of 81,718 AIHT cases in FinnGen and the UK Biobank, identifying 418 independent signals (P < 5 × 10−8). At 48 of these loci, a protein-coding variant is, or is highly correlated (r2 > 0.95) with, the lead variant, including Finnish-enriched coding variants in LAG3, ZAP70 and TG. We demonstrated that ZAP70:T155M reduces T cell activation and broadly compare large-scale scans of nonthyroid autoimmunity and thyroid-stimulating hormone levels with a Bayesian classifier to assign loci into distinct groupings, estimating that 38% are involved in general autoimmunity whereas 20% are thyroid specific. We further identified substantial antagonistic pleiotropy, with 10% of AIHT loci showing a consistent protective effect against skin cancer. The AIHT results, including numerous genes encoding checkpoint proteins, support the causal role of natural immune variation influencing cancer outcomes. Genome-wide analyses identify 418 independent associations with autoimmune hypothyroidism and classify risk loci into distinct groupings related to systemic autoimmunity and thyroid-specific dysfunction.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"550-559"},"PeriodicalIF":29.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-026-02521-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308465","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}

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YamHub as an international platform for yam research and breeding based in Guadeloupe YamHub是番薯研究和育种的国际平台，总部设在瓜德罗普岛

IF 29 1区生物学

Nature genetics Pub Date : 2026-02-24 DOI: 10.1038/s41588-026-02520-2

Komivi Dossa, Gemma Arnau, Erick Malédon, Elie Nudol, Marie-Claire Gravillon, Christophe Perrot, Lévy Laurent, Saskia Sergeant, Youri Uneau, Marie Umber, Delisia Casi, Jean-Luc Irep, David Hammouya, Sandrine Andypain, Olivier Hubert, Yolande Chilin-Charles, Jacques Louisor, Marcus Hery, Bertrand Fouks, Denis Cornet, Hanâ Chaïr

引用次数: 0

Three-dimensional genome reorganization foreshadows zygotic genome activation in Drosophila 三维基因组重组预示着果蝇的合子基因组激活

IF 29 1区生物学

Nature genetics Pub Date : 2026-02-24 DOI: 10.1038/s41588-026-02503-3

Noura Maziak, Yuchen Zhang, Fabian Groll, Haley E. Brown, Alla Madich, Yadwinder Kaur, Melissa M. Harrison, Jian Zhou, Juan M. Vaquerizas

{"title":"Three-dimensional genome reorganization foreshadows zygotic genome activation in Drosophila","authors":"Noura Maziak, Yuchen Zhang, Fabian Groll, Haley E. Brown, Alla Madich, Yadwinder Kaur, Melissa M. Harrison, Jian Zhou, Juan M. Vaquerizas","doi":"10.1038/s41588-026-02503-3","DOIUrl":"10.1038/s41588-026-02503-3","url":null,"abstract":"How chromatin conformation relates to chromatin state remains a central challenge in genome regulation. Here we present Pico-C, a low-input Micro-C approach that enables high-resolution, temporally resolved three-dimensional genome mapping during early Drosophila embryogenesis. Contrary to a prevailing view of a disorganized genome before zygotic genome activation (ZGA), we uncover a dynamic and ordered emergence of chromatin loops during pre-ZGA nuclear cycles. Spatial autocorrelation analysis points to context-dependent regulatory influences on chromatin. Notably, inhibition of transcriptional elongation has site-specific effects, retaining some early loops while weakening insulation at active promoters, suggesting distinct regulatory dependencies. Machine learning models trained on sequence features identify orthogonal, motif-specific contributions to architecture. Co-depletion of the pioneer factors Zelda and GAF leads to factor-specific perturbations in chromatin architecture, further highlighting a modular regulatory logic in genome establishment. Together, our findings reveal that early genome organization is orchestrated by an interplay of overlapping yet separable regulatory inputs. Pico-C, a low-input Micro-C approach, reveals that dynamic three-dimensional genome folding precedes zygotic genome activation in Drosophila.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"607-617"},"PeriodicalIF":29.0,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-026-02503-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147278973","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}

引用次数: 0

Harnessing wild relative diversity for engineering tomato resilience 利用野生相对多样性设计番茄抗逆性

IF 29 1区生物学

Nature genetics Pub Date : 2026-02-24 DOI: 10.1038/s41588-026-02510-4

引用次数: 0

Chromatin loop proteomics finds a non-catalytic function for a histone demethylase 染色质环蛋白质组学发现组蛋白去甲基化酶的非催化功能

IF 29 1区生物学

Nature genetics Pub Date : 2026-02-24 DOI: 10.1038/s41588-026-02519-9

Viviana I. Risca

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The role of KRAB zinc-finger proteins in expanding the domestication potential of transposable elements KRAB锌指蛋白在扩大转座因子驯化潜力中的作用。

IF 29 1区生物学

Nature genetics Pub Date : 2026-02-20 DOI: 10.1038/s41588-025-02498-3

Juliette Davis, Diana Voicu, Urvashi Chitnavis, Jeremi Jaksina, Michael Imbeault

{"title":"The role of KRAB zinc-finger proteins in expanding the domestication potential of transposable elements","authors":"Juliette Davis, Diana Voicu, Urvashi Chitnavis, Jeremi Jaksina, Michael Imbeault","doi":"10.1038/s41588-025-02498-3","DOIUrl":"10.1038/s41588-025-02498-3","url":null,"abstract":"KRAB zinc-finger proteins (KZFPs) are the most abundant family of DNA-binding proteins in humans and primarily induce the epigenetic silencing of transposable elements. While KZFPs use this ability to control the transposition potential of transposable elements, they can also act as epigenetic switches that gate transposable element-derived cis-regulatory modules in a cell context-specific manner. In this way, they participate in the domestication of mobile elements, expanding their ability to establish complex gene regulatory networks. In this Perspective, we discuss emerging evidence that mutations in KZFP genes can explain human disorders and that there is a need to understand the effect of mutations in their transposable element targets. We argue that increased focus on this large yet historically understudied family will greatly contribute to addressing gaps in our understanding of cell lineage specification during development, human phenotypes and related pathologies. This Perspective explores the co-evolution of transposable elements and KRAB zinc-finger proteins in relation to their integration into human gene regulatory networks, highlighting their potential effect on human phenotypes and disease.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"492-502"},"PeriodicalIF":29.0,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259061","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}

引用次数: 0

A tomato telomere-to-telomere super-pangenome empowers stress resilience breeding 番茄端粒到端粒的超级泛基因组增强了应激恢复育种能力

IF 29 1区生物学

Nature genetics Pub Date : 2026-02-18 DOI: 10.1038/s41588-026-02508-y

Chunmei Shi, Shaoying Chen, Jingxuan Wang, Weikai Chen, Congying Sun, Qiang Guo, Shenhao Liao, Huan Wang, Yupei Mu, Xin Shu, Dian Meng, Jiaojiao Zhao, Liepeng Dong, Lihua Zhao, Shuguo Hou, Li Guo, Changxian Yang

{"title":"A tomato telomere-to-telomere super-pangenome empowers stress resilience breeding","authors":"Chunmei Shi, Shaoying Chen, Jingxuan Wang, Weikai Chen, Congying Sun, Qiang Guo, Shenhao Liao, Huan Wang, Yupei Mu, Xin Shu, Dian Meng, Jiaojiao Zhao, Liepeng Dong, Lihua Zhao, Shuguo Hou, Li Guo, Changxian Yang","doi":"10.1038/s41588-026-02508-y","DOIUrl":"10.1038/s41588-026-02508-y","url":null,"abstract":"Tomato (Solanum lycopersicum), one of the world’s most valuable vegetable crops, has suffered from diminished genetic diversity and stress resistance. Wild tomatoes serve as an invaluable genetic reservoir, yet their potential for stress resilience remains largely unexploited in tomato breeding. Here we report a genus-wide super-pangenome across 16 tomato species by integrating 20 telomere-to-telomere genomes and 27 published chromosome-scale genomes. Genus-wide population analysis demonstrates broad genetic diversity with limited gene flows among principal clades. Pan-centromere analysis reveals a diverse landscape and dynamic evolution of the mysterious tomato centromeres involving rapid diversification, satellite emergence and repositioning. A comprehensive catalog of structural variants uncovers extensive rearrangements, especially from wild tomatoes, and discovers key molecular markers associated with salinity resistance. Structural-variant-based genome-wide association studies identified a leucine-rich repeat receptor gene SlGMAK conferring gray mold resistance. Our telomere-to-telomere super-pangenome will accelerate exploiting the untapped potential of wild relatives to improve modern tomatoes for stress resilience. A genus-wide super-pangenome across 16 tomato species generated by integrating 20 telomere-to-telomere genome assemblies and 27 published genomes identifies structural variants associated with salinity or disease resistance for molecular breeding.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"630-642"},"PeriodicalIF":29.0,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146210319","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}

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Author Correction: Single-cell atlas of the transcriptome and chromatin accessibility in the human retina 作者更正：人类视网膜中转录组和染色质可及性的单细胞图谱。

IF 29 1区生物学

Nature genetics Pub Date : 2026-02-18 DOI: 10.1038/s41588-026-02545-7

Jin Li, Jun Wang, Ignacio L. Ibarra, Xuesen Cheng, Malte D. Luecken, Jiaxiong Lu, Aboozar Monavarfeshani, Wenjun Yan, Yiqiao Zheng, Zhen Zuo, Samantha Lynn Zayas Colborn, Berenice Sarahi Cortez, Leah A. Owen, Brittney Wick, Xuan Bao, Jongsu Choi, Maximilian Haeussler, Nicholas M. Tran, Karthik Shekhar, Joshua R. Sanes, J. Timothy Stout, Shiming Chen, Yumei Li, Margaret M. DeAngelis, Fabian J. Theis, Rui Chen

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‘Non-coding’ GGC repeats are translated into toxic polyglycine proteins in neuromuscular diseases 在神经肌肉疾病中，“非编码”GGC重复序列被翻译成有毒的聚甘氨酸蛋白

IF 29 1区生物学

Nature genetics Pub Date : 2026-02-18 DOI: 10.1038/s41588-026-02517-x

引用次数: 0