Yang Lu, Zeyuan Wang, Shuyuan Zhang, Yaping Liu, Ye Jin, Zhuang Tian, Shuyang Zhang
{"title":"Genetic landscape of hereditary cardiomyopathies and arrhythmias in China.","authors":"Yang Lu, Zeyuan Wang, Shuyuan Zhang, Yaping Liu, Ye Jin, Zhuang Tian, Shuyang Zhang","doi":"10.1016/j.jgg.2025.07.003","DOIUrl":"https://doi.org/10.1016/j.jgg.2025.07.003","url":null,"abstract":"<p><p>Hereditary cardiomyopathies and arrhythmias are major contributors to cardiovascular morbidity and mortality. The advent of next-generation sequencing (NGS) has made genetic testing more accessible, which is crucial for precise diagnosis and targeted therapeutic strategies. The aim of this study is to explore the landscape of genetic variants, the relationship between specific variants and clinical phenotypes, and the impact on clinical decision-making in China. A total of 1,536 probands (median age, 37 years; 1,025 males [66.7%]) with suspected hereditary cardiomyopathy or arrhythmia (covering 15 clinical phenotypes) are recruited from 146 hospitals across 30 provinces and cities in China. Positive results are confirmed in 390 of 1536 probands, leading to a diagnostic yield of 25.4%. Forty-two and three tenths percent (n = 169) of family members carry the same variants as positive probands. Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the predominant phenotypes, with MYBPC3 variants having the highest frequency in HCM and TTN variants in DCM. In 76.9% of the positive probands, the identified variants are helpful in clinical management, family screening and fertility. This large-scale study provides significant insights into the genetic landscape of hereditary cardiomyopathies and arrhythmias in China.</p>","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627789","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}
Xingyue Xiao, Hongli Cheng, Jianghai Mo, Fan Sun, Qin Song, Chengshan Zhang, Pan Yang, Keming Luo, Hongbin Wei
{"title":"PHYTOCHROME-INTERACTING FACTOR3 (PIF3) orthologs orchestrate stem elongation and wood formation in Populus.","authors":"Xingyue Xiao, Hongli Cheng, Jianghai Mo, Fan Sun, Qin Song, Chengshan Zhang, Pan Yang, Keming Luo, Hongbin Wei","doi":"10.1016/j.jgg.2025.07.002","DOIUrl":"https://doi.org/10.1016/j.jgg.2025.07.002","url":null,"abstract":"<p><p>Phytochrome-interacting factors (PIFs) have been established as negative regulators of vascular patterning and xylem differentiation in the herbaceous plant Arabidopsis thaliana, however, PIFs' regulatory role in secondary growth in woody species remains unclear. Here, we examined the expression patterns and involvement of PtoPIF3.1 and PtoPIF3.2 during stem growth and secondary xylem development in Populus tomentosa. Overexpression of either PtoPIF3.1 or PtoPIF3.2 significantly enhances both longitudinal stem growth and radial wood development. Conversely, CRISPR-generated Ptopif3.1 and Ptopif3.2 mutants exhibit reciprocal phenotypic defects. Exogenous auxin application partially restores the phenotypes of Ptopif3.1 and Ptopif3.2 mutants, and the auxin biosynthesis-deficient mutant Ptoyuc8 exhibits developmental abnormalities similar to those observed in Ptopif3 mutants. Further analysis revealed that PtoPIF3s directly bind to and activate expression of PtoYUC8 and cell expansion-related genes PtoEXPA1.1/1.2, while modulating cambial division and secondary xylem development marker genes (PtoWOX4, PtoANT, PtoCYCD3s, and PtoHB7/8) through auxin-mediated signaling. Together, our findings establish PtoPIF3.1/3.2 as key regulators that coordinate stem elongation and secondary growth in Populus, highlighting the functional divergence of PIF homologs between herbaceous and woody species.</p>","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602279","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}
{"title":"USP21 deubiquitinates DPYSL2 and enhances its centrosomal abundance to promote cilium formation.","authors":"Ting Song, Peng Zhou, Fengguo Zhang, Chunli Liu, Xueqing Han, Yiyang Yue, Mingzheng Hu, Shaodong Yan, Qingchao Li, Min Liu, Jun Zhou, Huijie Zhao","doi":"10.1016/j.jgg.2025.06.006","DOIUrl":"https://doi.org/10.1016/j.jgg.2025.06.006","url":null,"abstract":"<p><p>Cilia are microtubule-based organelles projecting from the cell surface with important sensory and motility functions. Ciliary defects are associated with diverse diseases collectively known as ciliopathies. However, the molecular mechanisms that govern ciliogenesis remain not fully understood. Herein, we demonstrate that ubiquitin-specific protease 21 (USP21) is indispensable for cilium formation through its deubiquitinating activity. Usp21 knockout mice exhibit ciliary defects in multiple organs, such as the kidney, liver, and trachea. Our data also reveal a constant localization of USP21 at the centrosome and basal body during ciliogenesis. Mechanistically, USP21 interacts with dihydropyrimidinase-like 2 (DYPSL2) at the centrosome and removes lysine 48-linked ubiquitination from DYPSL2. Loss of USP21 leads to the proteasomal degradation of DPYSL2 and causes a significant reduction in its centrosome abundance, ultimately resulting in ciliary defects. These findings thus identify a critical role for the USP21-DPYSL2 axis in ciliogenesis and have important implications for health and disease.</p>","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576989","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}
{"title":"PenCards: a global and community-contributed public archive of variant penetrance.","authors":"Zhaopo Zhu, Ling Shang, Chuhan Shao, Zheng Wang, Xinxin Mao, Yuanfeng Huang, Pei Yu, Bin Li, Jinchen Li, Guihu Zhao","doi":"10.1016/j.jgg.2025.07.001","DOIUrl":"https://doi.org/10.1016/j.jgg.2025.07.001","url":null,"abstract":"<p><p>Penetrance is a crucial indicator for accurately assessing disease risk and plays a vital role in disease research, gene therapy, and genetic counseling. However, with penetrance data dispersed across various sources, efficiently accessing and consolidating this information becomes a challenge. A comprehensive platform that integrates penetrance is urgently needed. Here, we present PenCards, a global, community-contributed public archive of variant penetrance, by first collecting penetrance data from all published literature and then using large international cohorts to specifically calculate the penetrance of autism-related variants. PenCards contains a total of 244,531 variants-including 239,244 single nucleotide variants, 4,994 insertions and deletions, and 293 copy number variants, covering approximately 300 phenotypes. We also provide a submission portal for the dynamic updating of penetrance. Additionally, to help users efficiently access genetic information, we comprehensively integrate over 150 variant- and gene-level resources. In summary, PenCards is a powerful platform designed to advance genetic research and diagnostics. PenCards is publicly available at https://genemed.tech/pencards/.</p>","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576988","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}
Fengjun Xian, Shuya Liu, Bin Xie, Jishuai Huang, Qiannan Zhang, Yimeng Xu, Xinrong Zhang, Chen Lv, Lin Zhu, Jun Hu
{"title":"The auxin response factor OsARF12 modulates rice leaf angle via affecting shoot gravitropism.","authors":"Fengjun Xian, Shuya Liu, Bin Xie, Jishuai Huang, Qiannan Zhang, Yimeng Xu, Xinrong Zhang, Chen Lv, Lin Zhu, Jun Hu","doi":"10.1016/j.jgg.2025.06.005","DOIUrl":"https://doi.org/10.1016/j.jgg.2025.06.005","url":null,"abstract":"<p><p>Leaf angle is a pivotal agronomic trait that significantly influences crop architecture and yield. Plant hormones, such as auxin, play a critical role in regulating leaf angle; however, the underlying molecular mechanisms remain to be fully elucidated. Here, we reveal that the auxin response factor gene, OsARF12, which is highly expressed in the leaf lamina joint, negatively regulates rice (Oryza sativa) leaf angle via affecting shoot gravitropism. Overexpression lines of OsARF12 exhibit more erect leaf angles, while the osarf12 mutants display enlarged leaf angles compared to the wild type. Further studies demonstrate that OsARF12 directly activates the expression of Loose Plant Architecture1 (LPA1) and LAZY1 by binding to their promoters. The osarf12 mutant presents impaired shoot gravitropism, a phenotype consistent with that of the lpa1 or lazy1 mutant. Collectively, we elucidate the biological functions of OsARF12, which modulates leaf angle through its impact on shoot gravitropism by regulating the expression levels of LPA1 and LAZY1. This study provides insight into the role of auxin in determining rice leaf angle, potentially holding profound effects for the optimization of crop architecture.</p>","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565521","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}
{"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":"10.1016/j.jgg.2025.01.003","url":null,"abstract":"<p><p>The quantitative trait loci (QTL)-by-environment (Q × E) interaction effect is hard to detect because there are no effective ways to control the genomic background. In this study, we propose a 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 QTL 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 outperforms all other methods compared.</p>","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":"915-926"},"PeriodicalIF":6.6,"publicationDate":"2025-07-01","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}
{"title":"In vivo adenine base editing ameliorates Rho-associated autosomal dominant retinitis pigmentosa.","authors":"Sihui Hu, Yuxi Chen, Yitong Zhou, Tianqi Cao, Simiao Liu, Chenhui Ding, Dongchun Xie, Puping Liang, Li Huang, Haiying Liu, Junjiu Huang","doi":"10.1016/j.jgg.2024.12.012","DOIUrl":"10.1016/j.jgg.2024.12.012","url":null,"abstract":"<p><p>Mutations in the Rhodopsin (RHO) gene are the main cause of autosomal dominant retinitis pigmentosa (adRP), 84% of which are pathogenic gain-of-function point mutations. Treatment strategies for adRP typically involve silencing or ablating the pathogenic allele, while normal RHO protein replacement has no meaningful therapeutic benefit. Here, we present an adenine base editor (ABE)-mediated therapeutic approach for adRP caused by RHO point mutations in vivo. The correctable pathogenic mutations are screened and verified, including T17M, Q344ter, and P347L. Two adRP animal models are created carrying the class 1 (Q344ter) and class 2 (T17M) mutations, and dual AAV-delivered ABE can effectively repair both mutations in vivo. The early intervention of ABE8e efficiently corrects the Q344ter mutation that causes a severe form of adRP, delays photoreceptor death, and restores retinal function and visual behavior. These results suggest that ABE is a promising alternative to treat RHO mutation-associated adRP. Our work provides an effective spacer-mediated point mutation correction therapy for dominantly inherited ocular disorders.</p>","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":"887-900"},"PeriodicalIF":6.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900125","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}
Damin Yun, Sheng Gao, Xinyao Li, Jie Shi, Lingling Wang, Tiao Bu, Xiwen Yang, Yunhao Wu, Xiaolong Wu, Fei Sun
{"title":"The testis-specific gene 1700030J22Rikis essential for sperm flagellar function and male fertility in mice.","authors":"Damin Yun, Sheng Gao, Xinyao Li, Jie Shi, Lingling Wang, Tiao Bu, Xiwen Yang, Yunhao Wu, Xiaolong Wu, Fei Sun","doi":"10.1016/j.jgg.2024.12.010","DOIUrl":"10.1016/j.jgg.2024.12.010","url":null,"abstract":"<p><p>Spermiogenesis is an indispensable process occurring during the later stages of spermatogenesis. Despite multiple proteins being associated with spermiogenesis, the molecular mechanisms that control spermiogenesis remain poorly characterized. In this study, we show that 1700030J22Rik is exclusively expressed in testes of mice and investigate its roles in spermiogenesis using genetic and proteomic approaches. The deficiency in 1700030J22Rik in male mice results in severe subfertility, characterized by a substantial decrease in sperm concentration, motility, and abnormalities in the flagella. Furthermore, 1700030J22RIK interacts with the A-kinase-anchoring protein AKAP3, and 1700030J22Rik knockout decreases AKAP3 and AKAP4 protein levels. Additionally, the absence of 1700030J22RIK alters spermatozoal levels of the subunits of protein kinase A, leading to reduced protein phosphorylation and impaired sperm motility. This study reveals that 1700030J22Rik plays a crucial role in the organization of sperm morphology and function in mice.</p>","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":"927-941"},"PeriodicalIF":6.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878636","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}
Wenjuan Zhang, Shuang Wu, Yaxin Li, Mengye Cao, Biao Cao, Dantong Li, Kai Chen, Jian Zhao, Weijun Pan
{"title":"Characterization of zebrafish alas2 reporter for study on erythropoiesis, blood flow, and erythroid disease.","authors":"Wenjuan Zhang, Shuang Wu, Yaxin Li, Mengye Cao, Biao Cao, Dantong Li, Kai Chen, Jian Zhao, Weijun Pan","doi":"10.1016/j.jgg.2025.03.009","DOIUrl":"10.1016/j.jgg.2025.03.009","url":null,"abstract":"","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":"958-961"},"PeriodicalIF":6.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733256","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}
{"title":"Establishing a semi-homology-directed recombination method for precision gene integration in axolotls.","authors":"Liqun Wang, Yan Hu, Yuanhui Qiu, Huiting Lin, Xiang Li, Sulei Fu, Yan-Yun Zeng, Maria Ghouse, Cheng Long, Yanmei Liu, Ji-Feng Fei","doi":"10.1016/j.jgg.2025.03.001","DOIUrl":"10.1016/j.jgg.2025.03.001","url":null,"abstract":"<p><p>The axolotl is broadly used in regenerative, developmental, and evolutionary biology research. Targeted gene knock-in is crucial for precision transgenesis, enabling disease modeling, visualization, tracking, and functional manipulation of specific cells or genes of interest (GOIs). Existing CRISPR/Cas9-mediated homology-independent method for gene knock-in often causes \"scars/indels\" at integration junctions. Here, we develop a CRISPR/Cas9-mediated semi-homology-directed recombination (HDR) knock-in method using a donor construct containing a single homology arm for the precise integration of GOIs. This semi-HDR approach achieves seamless single-end integration of the Cherry reporter gene and a large inducible Cre cassette into intronless genes like Sox2 and Neurod6 in axolotls, which are challenging to modify with the homology-independent method. Additionally, we integrate the inducible Cre cassette into intron-containing loci (e.g., Nkx2.2 and FoxA2) without introducing indels via semi-HDR. GOIs are properly expressed in F0 founders, with approximately 5%-10% showing precise integration confirmed by genotyping. Furthermore, using the Nkx2.2:CreER<sup>T2</sup> line, we fate-map spinal cord p3 neural progenitor cells, revealing that Nkx2.2<sup>+</sup> cells adopt different lineages in development and regeneration, preferentially generating motoneurons over oligodendrocytes during regeneration. Overall, this semi-HDR method balances efficiency and precision in the integration of GOIs, providing a valuable tool for generating knock-in axolotls and potentially extending to other species.</p>","PeriodicalId":54825,"journal":{"name":"Journal of Genetics and Genomics","volume":" ","pages":"942-953"},"PeriodicalIF":6.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588292","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}