Human molecular genetics最新文献_第5页

Expanding scope of genetic studies in the era of biobanks. 在生物银行时代，基因研究的范围不断扩大。

IF 3.1 2区生物学

Human molecular genetics Pub Date : 2025-05-02 DOI: 10.1093/hmg/ddaf054

Diptavo Dutta, Nilanjan Chatterjee

{"title":"Expanding scope of genetic studies in the era of biobanks.","authors":"Diptavo Dutta, Nilanjan Chatterjee","doi":"10.1093/hmg/ddaf054","DOIUrl":"https://doi.org/10.1093/hmg/ddaf054","url":null,"abstract":"Biobanks have become pivotal in genetic research, particularly through genome-wide association studies (GWAS), driving transformative insights into the genetic basis of complex diseases and traits through the integration of genetic data with phenotypic, environmental, family history, and behavioral information. This review explores the distinct design and utility of different biobanks, highlighting their unique contributions to genetic research. We further discuss the utility and methodological advances in combining data from disease-specific study or consortia with that of biobanks, especially focusing on summary statistics based meta-analysis. Subsequently we review the spectrum of additional advantages offered by biobanks in genetic studies in representing population differences, calibration of polygenic scores, assessment of pleiotropy and improving post-GWAS in silico analyses. Advances in sequencing technologies, particularly whole-exome and whole-genome sequencing, have further enabled the discovery of rare variants at biobank scale. Among recent developments, the integration of large-scale multi-omics data especially proteomics and metabolomics, within biobanks provides deeper insights into disease mechanisms and regulatory pathways. Despite challenges like ascertainment strategies and phenotypic misclassification, biobanks continue to evolve, driving methodological innovation and enabling precision medicine. We highlight the contributions of biobanks to genetic research, their growing integration with multi-omics, and finally discuss their future potential for advancing healthcare and therapeutic development.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998551","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

Human and pathogen-encoded circular RNAs in viral infections: insights into functions and therapeutic opportunities. 病毒感染中的人类和病原体编码环状rna：对功能和治疗机会的见解。

IF 3.1 2区生物学

Human molecular genetics Pub Date : 2025-04-30 DOI: 10.1093/hmg/ddaf031

Noah L Mueller, Adela Dujsikova, Amrita Singh, Y Grace Chen

{"title":"Human and pathogen-encoded circular RNAs in viral infections: insights into functions and therapeutic opportunities.","authors":"Noah L Mueller, Adela Dujsikova, Amrita Singh, Y Grace Chen","doi":"10.1093/hmg/ddaf031","DOIUrl":"https://doi.org/10.1093/hmg/ddaf031","url":null,"abstract":"Circular RNAs (circRNAs) are emerging as important regulatory molecules in both host and viral systems, acting as microRNA sponges, protein decoys or scaffolds, and templates for protein translation. Host-derived circRNAs are increasingly recognized for their roles in immune responses, while virus-encoded circRNAs, especially those from DNA viruses, have been shown to modulate host cellular machinery to favor viral replication and immune evasion. Recently, RNA virus-encoded circRNAs were also discovered, but evidence suggests that they might be generated using a different mechanism compared to the circRNAs produced from the host and DNA viruses. This review highlights recent advances in our understanding of both host and virus-derived circRNAs, with a focus on their biological roles and contributions to pathogenesis. Furthermore, we discuss the potential of circRNAs as biomarkers and their application as therapeutic targets or scaffolds for RNA-based therapies. Understanding the roles of circRNAs in host-virus interactions offers novel insights into RNA biology and opens new avenues for therapeutic strategies against viral diseases and associated cancers.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994960","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

Inborn errors of canonical autophagy in neurodegenerative diseases. 神经退行性疾病典型自噬的先天性错误。

IF 3.1 2区生物学

Human molecular genetics Pub Date : 2025-04-30 DOI: 10.1093/hmg/ddae179

Dennis Freisem, Helene Hoenigsperger, Alberto Catanese, Konstantin M J Sparrer

{"title":"Inborn errors of canonical autophagy in neurodegenerative diseases.","authors":"Dennis Freisem, Helene Hoenigsperger, Alberto Catanese, Konstantin M J Sparrer","doi":"10.1093/hmg/ddae179","DOIUrl":"https://doi.org/10.1093/hmg/ddae179","url":null,"abstract":"Neurodegenerative disorders (NDDs), characterized by a progressive loss of neurons and cognitive function, are a severe burden to human health and mental fitness worldwide. A hallmark of NDDs such as Alzheimer's disease, Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and prion diseases is disturbed cellular proteostasis, resulting in pathogenic deposition of aggregated protein species. Autophagy is a major cellular process maintaining proteostasis and integral to innate immune defenses that mediates lysosomal protein turnover. Defects in autophagy are thus frequently associated with NDDs. In this review, we discuss the interplay between NDDs associated proteins and autophagy and provide an overview over recent discoveries in inborn errors in canonical autophagy proteins that are associated with NDDs. While mutations in autophagy receptors seems to be associated mainly with the development of ALS, errors in mitophagy are mainly found to promote PD. Finally, we argue whether autophagy may impact progress and onset of the disease, as well as the potential of targeting autophagy as a therapeutic approach. Concludingly, understanding disorders due to inborn errors in autophagy-\"autophagopathies\"-will help to unravel underlying NDD pathomechanisms and provide unique insights into the neuroprotective role of autophagy, thus potentially paving the way for novel therapeutic interventions.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998270","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

Driving Global Health equity and precision medicine through African genomic data. 通过非洲基因组数据推动全球卫生公平和精准医疗。

IF 3.1 2区生物学

Human molecular genetics Pub Date : 2025-04-30 DOI: 10.1093/hmg/ddaf025

Oyesola O Ojewunmi, Segun Fatumo

引用次数: 0

Single-cell transcriptome unveils mesenchymal cell diversity in endometriosis. 单细胞转录组揭示子宫内膜异位症的间充质细胞多样性。

IF 3.1 2区生物学

Human molecular genetics Pub Date : 2025-04-30 DOI: 10.1093/hmg/ddaf065

Xia Chen, Shengkun Zhang, Yujuan Qi, Tiantian Wu, Qiuru Huang, Xueyun Bao, Juan Gu, Qingqing Sun, Yueyue Shao, Nan Jiang, Ning Chen, Zhenbei Li, Sen Zheng, Xiangnan Cao, Jiaxin Li, Bo Zheng, Zhonghua Shi, Yijuan Cao, Xiaoli Sun, Jun Yu

{"title":"Single-cell transcriptome unveils mesenchymal cell diversity in endometriosis.","authors":"Xia Chen, Shengkun Zhang, Yujuan Qi, Tiantian Wu, Qiuru Huang, Xueyun Bao, Juan Gu, Qingqing Sun, Yueyue Shao, Nan Jiang, Ning Chen, Zhenbei Li, Sen Zheng, Xiangnan Cao, Jiaxin Li, Bo Zheng, Zhonghua Shi, Yijuan Cao, Xiaoli Sun, Jun Yu","doi":"10.1093/hmg/ddaf065","DOIUrl":"https://doi.org/10.1093/hmg/ddaf065","url":null,"abstract":"Mesenchymal cells constitute the primary structural support elements within endometriotic lesions, yet their pivotal roles in endometriotic pathogenesis remain largely uncharted. This study aimed to construct a single-cell atlas of endometriosis using samples from three ovarian tissues affected by endometriosis and three normal ovarian tissues. Through the utilization of scRNA-seq, we have unveiled six distinct mesenchymal subclusters in normal and endometriosis-afflicted ovaries, elucidating the diverse functions of mesenchymal populations in endometriosis. Our comprehensive analysis has revealed that mesenchymal cells predominantly engage in three key functions: ribosome-mediated protein synthesis and processing, cell adhesion facilitating intercellular support and communication, and a range of metabolic processes. Furthermore, our findings have identified several pivotal differentially expressed genes (e.g. C3, FN1, COL3A1, COL1A1, NRXN3), primarily associated with the complement and coagulation cascades, extracellular matrix (ECM) regulation, ECM receptor interactions, and cell adhesion molecules. In essence, our study provides a comprehensive transcriptomic dataset and novel insights into adhesive molecule and integrin networks within mesenchymal subclusters in endometriosis. This, in effect, has deepened the understanding of the pathomechanisms governing this condition.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002126","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

Loss of Nup160 dysregulates Cdc42 in the podocytes of podocyte-specific Nup160 knockout mice. 缺失Nup160会导致足细胞特异性Nup160敲除小鼠足细胞中的Cdc42失调。

IF 3.1 2区生物学

Human molecular genetics Pub Date : 2025-04-29 DOI: 10.1093/hmg/ddaf064

Deying Liu, Jiaxin Li, Chan Xu, Yuanyuan Li, Xiaohan Chen, Feng Zhao, Huajuan Tong, Yonghui Yang, Xiaojian Qiu, Zihua Yu

{"title":"Loss of Nup160 dysregulates Cdc42 in the podocytes of podocyte-specific Nup160 knockout mice.","authors":"Deying Liu, Jiaxin Li, Chan Xu, Yuanyuan Li, Xiaohan Chen, Feng Zhao, Huajuan Tong, Yonghui Yang, Xiaojian Qiu, Zihua Yu","doi":"10.1093/hmg/ddaf064","DOIUrl":"https://doi.org/10.1093/hmg/ddaf064","url":null,"abstract":"Mutations in four genes encoding the outer ring complex of nuclear pore complexes (NPCs), NUP85, NUP107, NUP133 and NUP160, cause monogenic steroid-resistant nephrotic syndrome (SRNS). Knockout of NUP85, NUP107, or NUP133 in immortalized human podocytes activates CDC42, an important effector of SRNS pathogenesis. However, it is unknown whether or not loss of NUP160 dysregulates CDC42 in the podocytes. Here, we generated a podocyte-specific Nup160 knockout mouse model with double-fluorescent (mT/mG) Cre reporter genes using CRISPR/Cas9 and Cre/loxP technologies. We investigated nephrotic syndrome-associated phenotypes in the Nup160podo-/- mice, and performed single-cell transcriptomic and proteomic analysis of glomerular suspension cells and cultured primary podocytes, respectively. The Nup160podo-/- mice exhibited progressive proteinuria and fusion of podocyte foot processes. We found decreased Cdc42 protein and normal Cdc42 transcriptional level in the podocytes of the Nup160podo-/- mice using analysis of single-cell transcriptomes and proteomes. We subsequently observed that Cdc42 protein decreased in both kidney tissues and cultured primary podocytes of the Nup160podo-/- mice, although Cdc42 mRNA levels were elevated in the cultured primary podocytes of the Nup160podo-/- mice. We also found that Cdc42 activity was significantly reduced in the cultured primary podocytes of the Nup160podo-/- mice. In conclusion, loss of Nup160 dysregulated Cdc42 in the podocytes of the Nup160podo-/- mice with proteinuria and fusion of podocyte foot processes. Our findings suggest that the dysregulation of CDC42 may contribute to the pathogenesis of SRNS in patients with mutations in NUP160.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998583","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 copper ionophore disulfiram improves mitochondrial function in various yeast and human cellular models of mitochondrial diseases. 铜离子载体二硫仑改善线粒体功能在各种酵母和线粒体疾病的人类细胞模型。

IF 3.1 2区生物学

Human molecular genetics Pub Date : 2025-04-29 DOI: 10.1093/hmg/ddaf061

Claire Almyre, Nolwenn Bounaix, François Godard, Olivier R Baris, Anne-Louise Cayer, Elodie Sardin, Marine Bouhier, Anaïs Hoarau, Laetitia Dard, Jérémy Richard, Vanessa Bergeron, Aurélie Renaud, Nadege Loaëc, Naïg Gueguen, Valérie Desquiret-Dumas, Bénédicte Lelievre, Aurore Inisan, Cristina Panozzo, Genevève Dujardin, Marc Blondel, Agnes Rötig, Véronique Paquis-Flucklinger, Stéphane Azoulay, Nathalie Bonnefoy, Carole H Sellem, Agnès Delahodde, Vincent Procaccio, Déborah Tribouillard-Tanvier

{"title":"The copper ionophore disulfiram improves mitochondrial function in various yeast and human cellular models of mitochondrial diseases.","authors":"Claire Almyre, Nolwenn Bounaix, François Godard, Olivier R Baris, Anne-Louise Cayer, Elodie Sardin, Marine Bouhier, Anaïs Hoarau, Laetitia Dard, Jérémy Richard, Vanessa Bergeron, Aurélie Renaud, Nadege Loaëc, Naïg Gueguen, Valérie Desquiret-Dumas, Bénédicte Lelievre, Aurore Inisan, Cristina Panozzo, Genevève Dujardin, Marc Blondel, Agnes Rötig, Véronique Paquis-Flucklinger, Stéphane Azoulay, Nathalie Bonnefoy, Carole H Sellem, Agnès Delahodde, Vincent Procaccio, Déborah Tribouillard-Tanvier","doi":"10.1093/hmg/ddaf061","DOIUrl":"https://doi.org/10.1093/hmg/ddaf061","url":null,"abstract":"The copper ionophore disulfiram (DSF) is commonly used to treat chronic alcoholism and has potential anti-cancer activity. Using a yeast-based screening assay of FDA-approved compounds, DSF was herein identified for its ability to improve oxidative phosphorylation-dependent growth of various yeast models of mitochondrial diseases caused by a wide range of defects in ATP synthase, complexes III and IV, cardiolipin remodeling, maintenance and translation of the mitochondrial genome. This compound also showed beneficial effects in cells derived from patients suffering from Barth or MELAS syndromes, two mitochondrial diseases associated respectively with a lack in cardiolipin remodeling and protein synthesis inside the organelle. We provide evidence that the rescuing activity of DSF results from its ability to transport copper ions across biological membranes. Indeed, other copper ionophores (pyrithione and elesclomol) and supplementation of the growth media with copper ions had also beneficial effects in yeast and human cells with dysfunctional mitochondria. Our data suggest that the copper-dependent rescuing activity in these cells results from a better capacity to assemble cytochrome c oxidase. Altogether, our findings hold promise for the development of new therapeutic strategies for mitochondrial disorders.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984483","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

STING: a multifaced player in cellular homeostasis. STING：细胞内稳态中的多面参与者。

IF 3.1 2区生物学

Human molecular genetics Pub Date : 2025-04-28 DOI: 10.1093/hmg/ddae175

Kun Song, Lyu Heng, Nan Yan

引用次数: 0

Recent developments in population biobanks and the genetic architecture of complex disease. 人口生物库的最新发展和复杂疾病的遗传结构。

IF 3.1 2区生物学

Human molecular genetics Pub Date : 2025-04-28 DOI: 10.1093/hmg/ddaf036

Samuel Khodursky, Nour Mimouni, Michael G Levin

引用次数: 0

The dynamic interactions between virus infections and nonsense-mediated decay. 病毒感染与无义介导的衰变之间的动态相互作用。