Journal of Genetics and Genomics最新文献_第4页

Metal ion transport in maize: survival in a variable stress environment. 金属离子在玉米中的转运：在可变胁迫环境中的生存。

IF 6.6 2区生物学

Journal of Genetics and Genomics Pub Date : 2025-01-15 DOI: 10.1016/j.jgg.2025.01.005

Kangqi Wang, Ziqi Wu, Man Zhang, Xueyao Lu, Jinsheng Lai, Meiling Zhang, Yi Wang

{"title":"Metal ion transport in maize: survival in a variable stress environment.","authors":"Kangqi Wang, Ziqi Wu, Man Zhang, Xueyao Lu, Jinsheng Lai, Meiling Zhang, Yi Wang","doi":"10.1016/j.jgg.2025.01.005","DOIUrl":"10.1016/j.jgg.2025.01.005","url":null,"abstract":"Maize (Zea mays) is the most widely cultivated crop in the world. Maize production is closely linked to the extensive uptake and utilization of various mineral nutrients. Potassium (K), calcium (Ca), and magnesium (Mg) are essential metallic macronutrients for plant growth and development. Sodium (Na) is an essential micronutrient for some C4 and CAM plants. Several metallic micronutrients like iron (Fe), manganese (Mn), and zinc (Zn) serve as enzyme components or co-factors in plant cells. Maize has to face the combined ion stress conditions in the natural environment. The limited availability of these nutrients in soils restricts maize production. In saline land, excessive Na could inhibit the uptake of mineral elements. Additionally, aluminum (Al) and heavy metal cadmium (Cd) and lead (Pb) in soils are toxic to maize and pose a threat to food security. Thus, plants must evolve complex mechanisms to increase nutrient uptake and utilization while restraining harmful elements. This review summarizes the research progress on the uptake and transport of metal ions in maize, highlights the regulation mechanism of metal ion transporters under stress conditions, and discusses the future challenges for the improvement of maize with high nutrient utilization efficiency (NUE).","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Biallelic variants in SREBF2 cause autosomal recessive spastic paraplegia. SREBF2的双等位基因变异导致常染色体隐性痉挛性截瘫。

IF 6.6 2区生物学

Journal of Genetics and Genomics Pub Date : 2025-01-14 DOI: 10.1016/j.jgg.2025.01.004

Qiao Wei, Wenlu Fan, Hong-Fu Li, Pei-Shan Wang, Man Xu, Hai-Lin Dong, Hao Yu, Jialan Lyu, Wen-Jiao Luo, Dian-Fu Chen, Wanzhong Ge, Zhi-Ying Wu

{"title":"Biallelic variants in SREBF2 cause autosomal recessive spastic paraplegia.","authors":"Qiao Wei, Wenlu Fan, Hong-Fu Li, Pei-Shan Wang, Man Xu, Hai-Lin Dong, Hao Yu, Jialan Lyu, Wen-Jiao Luo, Dian-Fu Chen, Wanzhong Ge, Zhi-Ying Wu","doi":"10.1016/j.jgg.2025.01.004","DOIUrl":"10.1016/j.jgg.2025.01.004","url":null,"abstract":"Hereditary spastic paraplegias (HSPs) refer to a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by the degeneration of motor neurons. To date, a significant number of patients still have not received a definite genetic diagnosis. Therefore, identifying unreported causative genes continues to be of great importance. Here, we perform whole exome sequencing in a cohort of Chinese HSP patients. Three homozygous variants (p.L604W, p.S517F, and p.T984A) within the sterol regulatory element-binding factor 2 (SREBF2) gene are identified in one autosomal recessive family and two sporadic patients, respectively. Co-segregation is confirmed by Sanger sequencing in all available members. The three variants are rare in the public or in-house database and are predicted to be damaging. The biological impacts of variants in SREBF2 are examined by functional experiments in patient-derived fibroblasts and Drosophila. We find that the variants upregulate cellular cholesterol due to the overactivation of SREBP2, eventually impairing the autophagosomal and lysosomal functions. The overexpression of the mature form of SREBP2 leads to locomotion defects in Drosophila. Our findings identify SREBF2 as a causative gene for HSP and highlight the impairment of cholesterol as a critical pathway for HSP.","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Identification of QTL-by-environment interaction by controlling polygenic background effect. 通过控制多基因背景效应鉴定环境互作qtl。

IF 6.6 2区生物学

Journal of Genetics and Genomics Pub Date : 2025-01-11 DOI: 10.1016/j.jgg.2025.01.003

Fuping Zhao, Lixian Wang, Shizhong Xu

{"title":"Identification of QTL-by-environment interaction by controlling polygenic background effect.","authors":"Fuping Zhao, Lixian Wang, Shizhong Xu","doi":"10.1016/j.jgg.2025.01.003","DOIUrl":"https://doi.org/10.1016/j.jgg.2025.01.003","url":null,"abstract":"The QTL by environment interaction (Q×E) effect is hard to detect because there are no effective ways to control the genomic background. In this study, we propose a novel linear mixed model that simultaneously analyzes data from multiple environments to detect Q×E interactions. This model incorporates two different kinship matrices derived from the genome-wide markers to control both main and interaction polygenic background effects. Simulation studies demonstrate that our approach is more powerful than the meta-analysis and inclusive composite interval mapping methods. We further analyze four agronomic traits of rice across four environments. A main effect QTL is identified for 1000-grain weight (KGW), while no QTLs are found for tiller number. Additionally, a large QTL with a significant Q×E interaction is detected on chromosome 7 affecting grain number, yield, and KGW. This region harbors two important genes, PROG1 and Ghd7. Furthermore, we apply our mixed model to analyze lodging in barley across six environments. The six regions exhibiting Q×E interaction effects identified by our approach overlap with the SNPs previously identified using EM and MCMC-based Bayesian methods, further validating the robustness of our approach. Both simulation studies and empirical data analyses show that our method outperformed all other methods compared.","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Enhancing crop yields to ensure food security by optimizing photosynthesis. 通过优化光合作用，提高作物产量，保障粮食安全。

IF 6.6 2区生物学

Journal of Genetics and Genomics Pub Date : 2025-01-10 DOI: 10.1016/j.jgg.2025.01.002

Chunrong Li, Xuejia Du, Cuimin Liu

{"title":"Enhancing crop yields to ensure food security by optimizing photosynthesis.","authors":"Chunrong Li, Xuejia Du, Cuimin Liu","doi":"10.1016/j.jgg.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.jgg.2025.01.002","url":null,"abstract":"The crop yields achieved through traditional plant breeding techniques appear to be nearing a plateau. Therefore, it is essential to accelerate advancements in photosynthesis, the fundamental process by which plants convert light energy into chemical energy, to further enhance crop yields. Research focused on improving photosynthesis holds significant promise for increasing sustainable agricultural productivity and addressing challenges related to global food security. This review examines the latest advancements and strategies aimed at boosting crop yields by enhancing photosynthetic efficiency. There has been a linear increase in yield over the years in historically released germplasm selected through traditional breeding methods, and this increase is accompanied by improved photosynthesis. We explore various aspects of the light reactions designed to enhance crop yield, including light harvest efficiency through smart canopy systems, expanding the absorbed light spectrum to include far-red light, optimizing non-photochemical quenching, and accelerating electron transport flux. At the same time, we investigate carbon reactions that can enhance crop yield, such as manipulating Rubisco activity, improving the Calvin-Benson-Bassham (CBB) cycle, introducing CO2 concentrating mechanisms (CCMs) in C3 plants, and optimizing carbon allocation. These strategies could significantly impact crop yield enhancement and help bridge the yield gap.","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Genomic characterization reveals distinct mutational landscape of acral melanoma in East Asian. 基因组特征揭示了东亚肢端黑色素瘤不同的突变景观。

IF 6.6 2区生物学

Journal of Genetics and Genomics Pub Date : 2025-01-09 DOI: 10.1016/j.jgg.2024.12.018

Fenghao Zhang, Xiaowen Wu, Tao Jiao, Haizhen Dua, Qian Guo, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Dezhi Jiang, Yuhong Zhang, Jiayan Wu, Yan Kong, Lu Si

{"title":"Genomic characterization reveals distinct mutational landscape of acral melanoma in East Asian.","authors":"Fenghao Zhang, Xiaowen Wu, Tao Jiao, Haizhen Dua, Qian Guo, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Dezhi Jiang, Yuhong Zhang, Jiayan Wu, Yan Kong, Lu Si","doi":"10.1016/j.jgg.2024.12.018","DOIUrl":"10.1016/j.jgg.2024.12.018","url":null,"abstract":"Acral melanoma, the most common melanoma subtype in East Asia, is associated with a poor prognosis. This study aims to comprehensively analyze the genomic characteristics of acral melanoma in East Asians. We conduct whole-genome sequencing of 55 acral melanoma tumors and perform data mining with relevant clinical data. Our findings reveal a unique mutational profile in East Asian acral melanoma, characterized by fewer point mutations and structural variations, a higher prevalence of NRAS mutations, and a lower frequency of BRAF mutations compared to patients of European descent. Notably, we identify previously underestimated ultraviolet radiation signatures and their significant association with BRAF and NRAS mutations. Structural rearrangement signatures indicate distinct mutational processes in BRAF-driven versus NRAS-driven tumors. We also find that homologous recombination deficiency with MAPK pathway mutations correlated with poor prognosis. The structural variations and amplifications in EP300, TERT, RAC1, and LZTR1 point to potential novel therapeutic targets tailored to East Asian populations. The high prevalence of whole-genome duplication events in BRAF/NRAS-mutated tumors suggests a synergistic carcinogenic effect that warrants further investigation. In summary, our study provides important insights into the genetic underpinnings of acral melanoma in East Asians, creating opportunities for targeted therapies.","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The maize mTERF18 regulates transcriptional termination of the mitochondrial nad6 gene and is essential for kernel development. 玉米mTERF18调控线粒体nad6基因的转录终止，对玉米籽粒发育至关重要。

IF 6.6 2区生物学

Journal of Genetics and Genomics Pub Date : 2025-01-09 DOI: 10.1016/j.jgg.2025.01.001

Zhengwei Guan, Yong Wang, Jun Yang

{"title":"The maize mTERF18 regulates transcriptional termination of the mitochondrial nad6 gene and is essential for kernel development.","authors":"Zhengwei Guan, Yong Wang, Jun Yang","doi":"10.1016/j.jgg.2025.01.001","DOIUrl":"10.1016/j.jgg.2025.01.001","url":null,"abstract":"Mitochondria are semi-autonomous organelles present in eukaryotic cells, containing their own genome and transcriptional machinery. However, their functions are intricately linked to proteins encoded by the nuclear genome. Mitochondrial transcription termination factors (mTERFs) are nucleic acid-binding proteins involved in RNA splicing and transcription termination within plant mitochondria and chloroplasts. Despite their recognized importance, the specific roles of mTERF proteins in maize remain largely unexplored. Here, we clone and functionally characterize the maize mTERF18 gene. Our findings reveal that mTERF18 mutations lead to severely undifferentiated embryos, resulting in abortive phenotypes. Early kernel exhibits abnormal basal endosperm transfer layer and a significant reduction in both starch and protein accumulation in mterf18. We identify the mTERF18 gene through mapping-based cloning and validate this gene through allelic tests. mTERF18 is widely expressed across various maize tissues and encodes a highly conserved mitochondrial protein. Transcriptome data reveal that mTERF18 mutations disrupt transcriptional termination of the nad6 gene, leading to undetectable levels of Nad6 protein and reduced complex I assembly and activity. Furthermore, transmission electron microscopy observation of mterf18 endosperm uncover severe mitochondrial defects. Collectively, these findings highlight the critical role of mTERF18 in mitochondrial gene transcription termination and its pivotal impact on maize kernel development.","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Deciphering the influence of gut and oral microbiomes on menopause for healthy aging. 解读肠道和口腔微生物群对更年期的影响，促进健康老龄化。

IF 6.6 2区生物学

Journal of Genetics and Genomics Pub Date : 2025-01-09 DOI: 10.1016/j.jgg.2024.11.010

Shuting Yu, Feiling Huang, Yixuan Huang, Fangxu Yan, Yi Li, Shenglong Xu, Yan Zhao, Xinlei Zhang, Rong Chen, Xingming Chen, Peng Zhang

{"title":"Deciphering the influence of gut and oral microbiomes on menopause for healthy aging.","authors":"Shuting Yu, Feiling Huang, Yixuan Huang, Fangxu Yan, Yi Li, Shenglong Xu, Yan Zhao, Xinlei Zhang, Rong Chen, Xingming Chen, Peng Zhang","doi":"10.1016/j.jgg.2024.11.010","DOIUrl":"10.1016/j.jgg.2024.11.010","url":null,"abstract":"Menopause is characterized by the cessation of menstruation and a decline in reproductive function, which is an intrinsic component of the aging process. However, it has been a frequently overlooked field of women's health. The oral and gut microbiota, constituting the largest ecosystem within the human body, are important for maintaining human health and notably contribute to the healthy aging of menopausal women. Therefore, a comprehensive review elucidating the impact of the gut and oral microbiota on menopause for healthy aging is of paramount importance. This paper presents the current understanding of the microbiome during menopause, with a particular focus on alterations in the oral and gut microbiota. Our study elucidates the complex interplay between the microbiome and sex hormone levels, explores microbial crosstalk dynamics, and investigates the associations between the microbiome and diseases linked to menopause. Additionally, this review explores the potential of microbiome-targeting therapies for managing menopause-related diseases. Given that menopause can last for approximately 30 years, gaining insights into how the microbiome and menopause interact could pave the way for innovative interventions, which may result in symptomatic relief from menopause and an increase in quality of life in women.","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Genetic interaction network of quantitative trait genes for heading date in rice. 水稻抽穗期数量性状基因的遗传互作网络。

IF 6.6 2区生物学

Journal of Genetics and Genomics Pub Date : 2025-01-06 DOI: 10.1016/j.jgg.2024.12.019

Mengjiao Chen, Yifeng Hong, Jiongjiong Fan, Dengyi Cao, Chong Yin, Anjie Yu, Jie Qiu, Xuehui Huang, Xin Wei

{"title":"Genetic interaction network of quantitative trait genes for heading date in rice.","authors":"Mengjiao Chen, Yifeng Hong, Jiongjiong Fan, Dengyi Cao, Chong Yin, Anjie Yu, Jie Qiu, Xuehui Huang, Xin Wei","doi":"10.1016/j.jgg.2024.12.019","DOIUrl":"https://doi.org/10.1016/j.jgg.2024.12.019","url":null,"abstract":"Several quantitative trait genes (QTGs) related to rice heading date, a key factor for crop development and yield, have been identified, along with complex interactions among genes. However, a comprehensive genetic interaction network for these QTGs has not yet been established. In this study, we use 18K-rice lines to identify QTGs and their epistatic interactions affecting rice heading date. We identify 264 pairs of interacting QTL and construct a comprehensive genetic network of these QTL. On average, the epistatic effects of QTL pairs are estimated to be approximately 12.5% of additive effects of identified QTL. Importantly, epistasis vary among different alleles of several heading date genes. Additionally, 57 pairs of interacting QTGs are also significant in their epistatic effects on 12 other agronomic traits. The identified QTL genetic interactions are further validated using near-isogenic lines, yeast two-hybrid, and split-luciferase complementation assays. Overall, this study provides a genetic network of rice heading date genes, which plays a crucial role in regulating rice heading date and influencing multiple related agronomic traits. This network serves as a foundation for understanding the genetic mechanisms of rice quantitative traits and for advancing molecular breeding efforts.","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Vitamin D receptor regulates methyltransferase like 14 to mitigate colitis-associated colorectal cancer. 维生素D受体调节甲基转移酶如14以减轻结肠炎相关结直肠癌。

IF 6.6 2区生物学

Journal of Genetics and Genomics Pub Date : 2025-01-06 DOI: 10.1016/j.jgg.2024.12.020

Zheng Wang, Lingjuan Jiang, Xiaoyin Bai, Mingyue Guo, Runing Zhou, Qingyang Zhou, Hong Yang, Jiaming Qian

{"title":"Vitamin D receptor regulates methyltransferase like 14 to mitigate colitis-associated colorectal cancer.","authors":"Zheng Wang, Lingjuan Jiang, Xiaoyin Bai, Mingyue Guo, Runing Zhou, Qingyang Zhou, Hong Yang, Jiaming Qian","doi":"10.1016/j.jgg.2024.12.020","DOIUrl":"https://doi.org/10.1016/j.jgg.2024.12.020","url":null,"abstract":"Colitis-associated colorectal cancer (CAC), a serious complication of ulcerative colitis (UC), is associated with a poor prognosis. The vitamin D receptor (VDR) is recognized for its protective role in UC and CAC through the maintenance of intestinal barrier integrity and the regulation of inflammation. This study demonstrates a significant reduction in m6A-related genes, particularly methyltransferase like 14 (METTL14), in UC and CAC patients and identifies an association between METTL14 and VDR. In the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced mouse model, vitamin D treatment increases METTL14 expression and reduces tumor burden, while Vdr-knockout mice exhibit lower METTL14 levels and increased tumorigenesis. In vitro, the VDR agonist calcipotriol upregulates METTL14 in NCM460 cells, with this effect attenuated by VDR knockdown. VDR knockdown in DLD-1 colon cancer cells decreases METTL14 expression and promotes proliferation, which is reversed by METTL14 overexpression. Mechanistic studies reveal that VDR regulates METTL14 expression via promoter binding, modulating key target genes such as SOX4, DROSH, and PHLPP2. This study highlights the role of the VDR-METTL14 axis as a protective mechanism in CAC and suggests its potential as a therapeutic target for preventing and treating CAC.","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Improving precision base editing of the zebrafish genome by Rad51DBD-incorporated single-base editors. 通过 Rad51DBD 导入单碱基编辑器改进斑马鱼基因组的精确碱基编辑。

IF 6.6 2区生物学

Journal of Genetics and Genomics Pub Date : 2025-01-01 Epub Date: 2024-10-18 DOI: 10.1016/j.jgg.2024.10.006

Zhilin Zhong, Xueli Hu, Renjie Zhang, Xu Liu, Wenqi Chen, Shubin Zhang, Jianjian Sun, Tao P Zhong

{"title":"Improving precision base editing of the zebrafish genome by Rad51DBD-incorporated single-base editors.","authors":"Zhilin Zhong, Xueli Hu, Renjie Zhang, Xu Liu, Wenqi Chen, Shubin Zhang, Jianjian Sun, Tao P Zhong","doi":"10.1016/j.jgg.2024.10.006","DOIUrl":"10.1016/j.jgg.2024.10.006","url":null,"abstract":"Single-base editors, including cytosine base editors (CBEs) and adenine base editors (ABEs), facilitate accurate C⋅G to T⋅A and A⋅T to G⋅C, respectively, holding promise for the precise modeling and treatment of human hereditary disorders. Efficient base editing and expanded base conversion range have been achieved in human cells through base editors fusing with Rad51 DNA binding domain (Rad51DBD), such as hyA3A-BE4max. Here, we show that hyA3A-BE4max catalyzes C-to-T substitution in the zebrafish genome and extends editing positions (C12-C16) proximal to the protospacer adjacent motif. We develop a codon-optimized counterpart zhyA3A-CBE5, which exhibits substantially high C-to-T conversion with 1.59- to 3.50-fold improvement compared with the original hyA3A-BE4max. With these tools, disease-relevant hereditary mutations can be more efficaciously generated in zebrafish. We introduce human genetic mutation rpl11Q42∗ and abcc6aR1463C by zhyA3A-CBE5 in zebrafish, mirroring Diamond-Blackfan anemia and Pseudoxanthoma Elasticum, respectively. Our study expands the base editing platform targeting the zebrafish genomic landscape and the application of single-base editors for disease modeling and gene function study.","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":"105-115"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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