Human molecular genetics最新文献_第10页

Functional characterization of OXTR-associated enhancers. oxtr相关增强子的功能表征。

IF 3.1 2区生物学

Human molecular genetics Pub Date : 2025-05-06 DOI: 10.1093/hmg/ddaf022

Dianne Laboy Cintrón, Rory R Sheng, Nadav Ahituv

引用次数: 0

Aggregates associated with amyotrophic lateral sclerosis sequester the actin-binding protein profilin 2. 与肌萎缩性侧索硬化症相关的聚集体隔离肌动蛋白结合蛋白2。

IF 3.1 2区生物学

Human molecular genetics Pub Date : 2025-05-06 DOI: 10.1093/hmg/ddaf020

Sabrina Kubinski, Luisa Claus, Tobias Schüning, Andre Zeug, Norman Kalmbach, Selma Staege, Thomas Gschwendtberger, Susanne Petri, Florian Wegner, Peter Claus, Niko Hensel

{"title":"Aggregates associated with amyotrophic lateral sclerosis sequester the actin-binding protein profilin 2.","authors":"Sabrina Kubinski, Luisa Claus, Tobias Schüning, Andre Zeug, Norman Kalmbach, Selma Staege, Thomas Gschwendtberger, Susanne Petri, Florian Wegner, Peter Claus, Niko Hensel","doi":"10.1093/hmg/ddaf020","DOIUrl":"10.1093/hmg/ddaf020","url":null,"abstract":"Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterized by the degeneration of upper and lower motoneurons. The four most frequently mutated genes causing familial ALS (fALS) are C9orf72, FUS, SOD1, and TARDBP. Some of the related wild-type proteins comprise intrinsically disordered regions (IDRs) which favor their assembly in liquid droplets-the biophysical mechanism behind the formation of physiological granules such as stress granules (SGs). SGs assemble and dissolve dependent on the cellular condition. However, it has been suggested that transition from reversible SGs to irreversible aggregates contributes to the toxic properties of ALS-related mutated proteins. Sequestration of additional proteins within these aggregates may then result in downstream toxicity. While the exact downstream mechanisms remain elusive, rare ALS-causing mutations in the actin binding protein profilin 1 suggest an involvement of the actin cytoskeleton. Here, we hypothesize that profilin isoforms become sequestered in aggregates of ALS-associated proteins which induce subsequent dysregulation of the actin cytoskeleton. Interestingly, localization of neuronal profilin 2 in SGs was more pronounced compared with the ubiquitously expressed profilin 1. Accordingly, FUS and C9orf72 aggregates prominently sequestered profilin 2 but not profilin 1. Moreover, we observed a distinct sequestration of profilin 2 and G-actin to C9orf72 aggregates in different cellular models. On the functional level, we identified dysregulated actin dynamics in cells with profilin 2-sequestering aggregates. In summary, our results suggest a more common involvement of profilins in ALS pathomechanisms than indicated from the rarely occurring profilin mutations.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"882-893"},"PeriodicalIF":3.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596768","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

Diverse landscape of genomic research within the Estonian Biobank. 爱沙尼亚生物库内基因组研究的多样化景观。

IF 3.1 2区生物学

Human molecular genetics Pub Date : 2025-05-02 DOI: 10.1093/hmg/ddaf026

Reedik Mägi

引用次数: 0

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":"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

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。