Nature genetics最新文献

Overcoming challenges associated with broad sharing of human genomic data

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-01-22 DOI: 10.1038/s41588-024-02049-2

Jonathan E. LoTempio, Jonathan D. Moreno

引用次数: 0

In vivo CRISPR–Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington’s disease

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-01-22 DOI: 10.1038/s41588-024-02054-5

Ricardo Mouro Pinto, Ryan Murtha, António Azevedo, Cameron Douglas, Marina Kovalenko, Jessica Ulloa, Steven Crescenti, Zoe Burch, Esaria Oliver, Maheswaran Kesavan, Shota Shibata, Antonia Vitalo, Eduarda Mota-Silva, Marion J. Riggs, Kevin Correia, Emanuela Elezi, Brigitte Demelo, Jeffrey B. Carroll, Tammy Gillis, James F. Gusella, Marcy E. MacDonald, Vanessa C. Wheeler

{"title":"In vivo CRISPR–Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington’s disease","authors":"Ricardo Mouro Pinto, Ryan Murtha, António Azevedo, Cameron Douglas, Marina Kovalenko, Jessica Ulloa, Steven Crescenti, Zoe Burch, Esaria Oliver, Maheswaran Kesavan, Shota Shibata, Antonia Vitalo, Eduarda Mota-Silva, Marion J. Riggs, Kevin Correia, Emanuela Elezi, Brigitte Demelo, Jeffrey B. Carroll, Tammy Gillis, James F. Gusella, Marcy E. MacDonald, Vanessa C. Wheeler","doi":"10.1038/s41588-024-02054-5","DOIUrl":"https://doi.org/10.1038/s41588-024-02054-5","url":null,"abstract":"Huntington’s disease, one of more than 50 inherited repeat expansion disorders1, is a dominantly inherited neurodegenerative disease caused by a CAG expansion in HTT2. Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the disease is driven by the CAG length-dependent propensity of the repeat to further expand in the brain3,4,5,6,7,8,9. Routes to slowing somatic CAG expansion, therefore, hold promise for disease-modifying therapies. Several DNA repair genes, notably in the mismatch repair pathway, modify somatic expansion in Huntington’s disease mouse models10. To identify novel modifiers of somatic expansion, we used CRISPR–Cas9 editing in Huntington’s disease knock-in mice to enable in vivo screening of expansion-modifier candidates at scale. This included testing of Huntington’s disease onset modifier genes emerging from human genome-wide association studies as well as interactions between modifier genes, providing insight into pathways underlying CAG expansion and potential therapeutic targets.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"32 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992382","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

Defining genes and pathways that modify huntingtin CAG repeat somatic instability in vivo

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-01-22 DOI: 10.1038/s41588-024-02055-4

Suphinya Sathitloetsakun, Myriam Heiman

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Author Correction: The ZmCPK39–ZmDi19–ZmPR10 immune module regulates quantitative resistance to multiple foliar diseases in maize 作者更正：ZmCPK39-ZmDi19-ZmPR10 免疫模块调控玉米对多种叶面病害的定量抗性

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-01-21 DOI: 10.1038/s41588-025-02091-8

Mang Zhu, Tao Zhong, Ling Xu, Chenyu Guo, Xiaohui Zhang, Yulin Liu, Yan Zhang, Yancong Li, Zhijian Xie, Tingting Liu, Fuyan Jiang, Xingming Fan, Peter Balint-Kurti, Mingliang Xu

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Author Correction: A multilineage screen identifies actionable synthetic lethal interactions in human cancers

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-01-20 DOI: 10.1038/s41588-025-02090-9

Samson H. Fong, Brent M. Kuenzi, Nicole M. Mattson, John Lee, Kyle Sanchez, Ana Bojorquez-Gomez, Kyle Ford, Brenton P. Munson, Katherine Licon, Sarah Bergendahl, John Paul Shen, Jason F. Kreisberg, Prashant Mali, Jeffrey H. Hager, Michael A. White, Trey Ideker

引用次数: 0

Nucleotide-resolution DNA foundation models of prokaryotic genomes

IF 31.7 1区生物学

Nature genetics Pub Date : 2025-01-15 DOI: 10.1038/s41588-024-02062-5

Michael Fletcher

引用次数: 0

Brain metastasis prediction

IF 31.7 1区生物学

Nature genetics Pub Date : 2025-01-15 DOI: 10.1038/s41588-024-02061-6

Tiago Faial

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Mutations in healthy breast tissue

IF 31.7 1区生物学

Nature genetics Pub Date : 2025-01-15 DOI: 10.1038/s41588-024-02060-7

Safia Danovi

引用次数: 0

Behavioral insights from single-nucleus neuronal transcriptomics

IF 31.7 1区生物学

Nature genetics Pub Date : 2025-01-15 DOI: 10.1038/s41588-024-02063-4

Petra Gross

引用次数: 0

Multi-omic quantitative trait loci link tandem repeat size variation to gene regulation in human brain 多组学定量性状位点将串联重复大小变异与人脑基因调控联系起来

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-01-14 DOI: 10.1038/s41588-024-02057-2

Ya Cui, Frederick J. Arnold, Jason Sheng Li, Jie Wu, Dan Wang, Julien Philippe, Michael R. Colwin, Sebastian Michels, Chaorong Chen, Tamer Sallam, Leslie M. Thompson, Albert R. La Spada, Wei Li

{"title":"Multi-omic quantitative trait loci link tandem repeat size variation to gene regulation in human brain","authors":"Ya Cui, Frederick J. Arnold, Jason Sheng Li, Jie Wu, Dan Wang, Julien Philippe, Michael R. Colwin, Sebastian Michels, Chaorong Chen, Tamer Sallam, Leslie M. Thompson, Albert R. La Spada, Wei Li","doi":"10.1038/s41588-024-02057-2","DOIUrl":"https://doi.org/10.1038/s41588-024-02057-2","url":null,"abstract":"Tandem repeat (TR) size variation is implicated in ~50 neurological disorders, yet its impact on gene regulation in the human brain remains largely unknown. In the present study, we quantified the impact of TR size variation on brain gene regulation across distinct molecular phenotypes, based on 4,412 multi-omics samples from 1,597 donors, including 1,586 newly sequenced ones. We identified ~2.2 million TR molecular quantitative trait loci (TR-xQTLs), linking ~139,000 unique TRs to nearby molecular phenotypes, including many known disease-risk TRs, such as the G2C4 expansion in C9orf72 associated with amyotrophic lateral sclerosis. Fine-mapping revealed ~18,700 TRs as potential causal variants. Our in vitro experiments further confirmed the causal and independent regulatory effects of three TRs. Additional colocalization analysis indicated the potential causal role of TR variation in brain-related phenotypes, highlighted by a 3ʹ-UTR TR in NUDT14 linked to cortical surface area and a TG repeat in PLEKHA1, associated with Alzheimer’s disease.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"27 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974575","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