Nature genetics最新文献_第6页

Contribution of copy number variants to schizophrenia in East Asian populations 东亚人群中拷贝数变异对精神分裂症的贡献

IF 25.5 1区生物学

Nature genetics Pub Date : 2026-09-11 DOI: 10.1038/s41588-026-02732-6

Yu Chen, Qidi Feng, Max Lam, Mingrui Yu, Yaoyao Sun, Cong Huai, Bimal Jana, Jack Fu, Calwing Liao, Robert Ye, Soyeon Kim, Justin D. Tubbs, Omar Shanta, Bhooma Thiruvahindrapuram, Yawen Jen, Guorui Zhao, Jess Wang, Stanley Global Asia Initiatives, Juan Xu, Wenzhao Shi, Stephen W. Scherer, Feng Zhu, Chih-Min Liu, Zhenglin Guo, Daniel Howrigan, Mark Daly, Benjamin M. Neale, Akira Sawa, Jonathan Sebat, Michael E. Talkowski, Jinsong Tang, Xiancang Ma, Wei J. Chen, Shengying Qin, Weihua Yue, Tian Ge, Hailiang Huang

{"title":"Contribution of copy number variants to schizophrenia in East Asian populations","authors":"Yu Chen, Qidi Feng, Max Lam, Mingrui Yu, Yaoyao Sun, Cong Huai, Bimal Jana, Jack Fu, Calwing Liao, Robert Ye, Soyeon Kim, Justin D. Tubbs, Omar Shanta, Bhooma Thiruvahindrapuram, Yawen Jen, Guorui Zhao, Jess Wang, Stanley Global Asia Initiatives, Juan Xu, Wenzhao Shi, Stephen W. Scherer, Feng Zhu, Chih-Min Liu, Zhenglin Guo, Daniel Howrigan, Mark Daly, Benjamin M. Neale, Akira Sawa, Jonathan Sebat, Michael E. Talkowski, Jinsong Tang, Xiancang Ma, Wei J. Chen, Shengying Qin, Weihua Yue, Tian Ge, Hailiang Huang","doi":"10.1038/s41588-026-02732-6","DOIUrl":"10.1038/s41588-026-02732-6","url":null,"abstract":"Studies on schizophrenia-associated rare copy number variants (CNVs) have predominantly focused on people of European (EUR) ancestry. Here we present a rare CNV study of schizophrenia in East Asian (EAS) populations, comprising 20,903 cases and 23,258 controls. We observed a significantly elevated genome-wide rare CNV burden in EAS cases compared with controls. Cross-population comparisons showed largely consistent rare CNV effects on schizophrenia risk. In the EAS sample, we identified nine genome-wide-significant schizophrenia-associated rare CNV loci. Meta-analysis with EUR data yielded 14 significant loci, including 8 that reached genome-wide significance for the first time. Genes within these 14 loci were significantly less tolerant to loss-of-function variants than genes in other CNV loci. The new rare CNVs associated with schizophrenia in EAS populations showed higher carrier frequencies in EAS than in EUR populations (0.38% versus 0.0017%). Overall, this study underscores the importance of increasing population diversity to fully capture the genetic underpinnings of schizophrenia. Genomic analyses in populations of East Asian ancestry identify rare copy number variants associated with schizophrenia. Meta-analyses with populations of European ancestry identify additional risk loci enriched in genes less tolerant to loss-of-function variants.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 10","pages":"2514-2524"},"PeriodicalIF":25.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-026-02732-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148934009","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

Applying the FDA's plausible mechanism guidance across the rare disease landscape. 在罕见病领域应用FDA貌似合理的机制指导。

IF 25.5 1区生物学

Nature genetics Pub Date : 2026-09-09 DOI: 10.1038/s41588-026-02750-4

Caroline Hendry, Jiangbing Zhou, Yong-Hui Jiang

引用次数: 0

Cohesin prevents local mixing of condensed euchromatic domains in living human cells 内聚蛋白可防止活细胞中凝聚的共色结构域的局部混合

IF 25.5 1区生物学

Nature genetics Pub Date : 2026-09-08 DOI: 10.1038/s41588-026-02736-2

Masa A. Shimazoe, Shiori Iida, Katsuhiko Minami, Koichi Higashi, Sachiko Tamura, Yoshiaki Kobayashi, Shin Fujishiro, Le Xiong, Kako Nakazato, S. S. Ashwin, Tomoko Nishiyama, Yu Nagata, Masato T. Kanemaki, Akane Kawaguchi, Yasuyuki Ohkawa, Lothar Schermelleh, Atsushi Toyoda, Liangqi Xie, Ken Kurokawa, Hiroshi Ochiai, Masaki Sasai, Kazuhiro Maeshima

{"title":"Cohesin prevents local mixing of condensed euchromatic domains in living human cells","authors":"Masa A. Shimazoe, Shiori Iida, Katsuhiko Minami, Koichi Higashi, Sachiko Tamura, Yoshiaki Kobayashi, Shin Fujishiro, Le Xiong, Kako Nakazato, S. S. Ashwin, Tomoko Nishiyama, Yu Nagata, Masato T. Kanemaki, Akane Kawaguchi, Yasuyuki Ohkawa, Lothar Schermelleh, Atsushi Toyoda, Liangqi Xie, Ken Kurokawa, Hiroshi Ochiai, Masaki Sasai, Kazuhiro Maeshima","doi":"10.1038/s41588-026-02736-2","DOIUrl":"10.1038/s41588-026-02736-2","url":null,"abstract":"The human genome is folded into chromatin loops by the cohesin complex, forming functional chromatin domains that underlie transcription and DNA replication/repair. However, how cohesin organizes these domains in living cells, especially in active euchromatin, remains elusive. Here, to address this question, we combined single-nucleosome imaging/tracking and super-resolution three-dimensional structured illumination microscopy with euchromatin-specific labeling of histone variant H3.3. Using this nanoscopic approach, we revealed that euchromatin forms condensed domains that are constrained by cohesin-mediated loops. This organization refines the classical view of euchromatin as largely open, in line with emerging evidence. Transcription machinery appears to be located near the condensed domain surfaces/borders. Cohesin loss increased nucleosome-level fluidity within these domains without altering their overall compaction, leading to local mixing of domains and compromising transcriptional insulation. These findings suggest a physical role of cohesin in maintaining the integrity of condensed euchromatic domains and ensuring proper higher-order regulation of gene expression. Single-nucleosome imaging/tracking and super-resolution three-dimensional structured illumination microscopy within euchromatic regions show that cohesin-mediated loops constrain condensed euchromatic domains. Cohesin loss increases their fluidity without affecting their overall compaction, leading to local domain mixing and compromised transcriptional insulation.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 9","pages":"2335-2349"},"PeriodicalIF":25.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-026-02736-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904485","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

A cancer that swims between hosts 在宿主之间游走的癌症

IF 25.5 1区生物学

Nature genetics Pub Date : 2026-09-08 DOI: 10.1038/s41588-026-02760-2

Hui Hua

引用次数: 0

T2T-HG002v1.1 human genome benchmark T2T-HG002v1.1人类基因组基准

IF 25.5 1区生物学

Nature genetics Pub Date : 2026-09-08 DOI: 10.1038/s41588-026-02761-1

Wei Li

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Human and mouse adrenal glands are characterized by species-specific steroidogenic states and tissue turnover 人和小鼠肾上腺的特点是物种特异性的类固醇生成状态和组织周转

IF 25.5 1区生物学

Nature genetics Pub Date : 2026-09-08 DOI: 10.1038/s41588-026-02737-1

Maria E. Kastriti, Denis Maksimov, Julia Krupinova, Marina Utkina, Dmitry Beltsevich, Anna Roslyakova, Olga Glazova, Samira Kaziakhmedova, Alina Ryabova, Anna Kuznetsova, Anastasia Shcherbakova, Ekaterina Bondarenko, Zoia Antysheva, Eugene Albert, Lilia Urusova, Anastasia Lapshina, Anastassia Chevais, Ekaterina Avsievich, Valentin Trofimov, Galina Melnichenko, Natalya Mokrysheva, Ivan Dedov, Lukas Englmaier, Julian Petersen, Oleg Gusev, Andreas Heinzel, Rainer Oberbauer, Pavel Volchkov, Peter V. Kharchenko, Igor Adameyko

{"title":"Human and mouse adrenal glands are characterized by species-specific steroidogenic states and tissue turnover","authors":"Maria E. Kastriti, Denis Maksimov, Julia Krupinova, Marina Utkina, Dmitry Beltsevich, Anna Roslyakova, Olga Glazova, Samira Kaziakhmedova, Alina Ryabova, Anna Kuznetsova, Anastasia Shcherbakova, Ekaterina Bondarenko, Zoia Antysheva, Eugene Albert, Lilia Urusova, Anastasia Lapshina, Anastassia Chevais, Ekaterina Avsievich, Valentin Trofimov, Galina Melnichenko, Natalya Mokrysheva, Ivan Dedov, Lukas Englmaier, Julian Petersen, Oleg Gusev, Andreas Heinzel, Rainer Oberbauer, Pavel Volchkov, Peter V. Kharchenko, Igor Adameyko","doi":"10.1038/s41588-026-02737-1","DOIUrl":"10.1038/s41588-026-02737-1","url":null,"abstract":"The adult adrenal cortex undergoes constant renewal, yet underlying human-specific mechanisms remain poorly understood. Here we generated single-cell and spatial transcriptomic atlases of adult human and mouse adrenal glands, leveraging single-cell-resolution spatial data and a rare clonal mosaic case for lineage inference. In humans, we identified age-associated zona glomerulosa (ZG) cell states with direct cortisol synthesis capacity and sex-specific differences in inferred cholesterol balance. Cross-species comparison revealed conserved aldosterone-producing ZG but notable divergence in zona fasciculata markers, absence of zona reticularis homologs in mice and differential SHH–WNT4 signaling in proliferating cells. We uncovered human WT1− capsule-to-ZG transition and vascular smooth muscle cell-to-steroidogenic transitions supported by mosaic lineage evidence. We revealed dispersed proliferating cortical SF1+EZH2+ cells throughout the human cortex in contrast with ZG restriction in mice. Taken together, our data expand the centripetal renewal model and establish a comparative framework for human adrenocortical biology. The authors present a comprehensive comparative resource for adult human and mouse adrenal glands through single-cell and spatial transcriptomic analyses.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 9","pages":"2270-2283"},"PeriodicalIF":25.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-026-02737-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904404","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

Emerging antimalarial resistance haplotype 新出现的抗疟单倍型

IF 25.5 1区生物学

Nature genetics Pub Date : 2026-09-08 DOI: 10.1038/s41588-026-02762-0

Kyle Vogan

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Mechanisms underlying disease-causing variants in promoters and enhancers 启动子和增强子致病变异的机制。

IF 25.5 1区生物学

Nature genetics Pub Date : 2026-09-08 DOI: 10.1038/s41588-026-02743-3

Hannah K. Long, Kun Wu (, ), Ryan S. Barkham, Wendy A. Bickmore

引用次数: 0

Tracing ‘ghost’ ancestry in modern humans 追踪现代人类的“幽灵”祖先

IF 25.5 1区生物学

Nature genetics Pub Date : 2026-09-08 DOI: 10.1038/s41588-026-02759-9

Petra Gross

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Training as infrastructure for biological data science in wartime Ukraine 乌克兰战时生物数据科学基础设施的培训

IF 25.5 1区生物学

Nature genetics Pub Date : 2026-09-07 DOI: 10.1038/s41588-026-02702-y

Taras K. Oleksyk, Lada H. Isakova, Yevheniia Haiovych, Oleksii Kurutsa, Serhii Vronskiy, Borys Olifirov, Oleh Mezhenskyi, Anastasiia Horlova, Daryna Zavadska, Valeriia Vasylieva, Helena L. Crowell, Walter Wolfsberger, Roderic Guigó, Wolfgang Huber, Serghei Mangul, Fyodor A. Kondrashov, on behalf of the UBDS³ Faculty Consortium

引用次数: 0