Pub Date : 2024-03-12DOI: 10.1038/s41576-024-00722-0
Kirsty Minton
A study in Science reports that corn snakes use both PRDM9 and promoter-like features to direct meiotic recombination, indicating that these are not mutually exclusive.
{"title":"Competition between sites of meiotic recombination in snakes","authors":"Kirsty Minton","doi":"10.1038/s41576-024-00722-0","DOIUrl":"10.1038/s41576-024-00722-0","url":null,"abstract":"A study in Science reports that corn snakes use both PRDM9 and promoter-like features to direct meiotic recombination, indicating that these are not mutually exclusive.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":null,"pages":null},"PeriodicalIF":42.7,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110884","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}
Pub Date : 2024-03-11DOI: 10.1038/s41576-024-00719-9
Henry Ertl
A study in Nature Genetics identifies many regulators of genome-wide chromatin accessibility and then reports the mechanistic underpinnings for one of the identified transcription factors.
{"title":"The regulatory landscape of chromatin accessibility","authors":"Henry Ertl","doi":"10.1038/s41576-024-00719-9","DOIUrl":"10.1038/s41576-024-00719-9","url":null,"abstract":"A study in Nature Genetics identifies many regulators of genome-wide chromatin accessibility and then reports the mechanistic underpinnings for one of the identified transcription factors.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":null,"pages":null},"PeriodicalIF":42.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140096941","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}
Pub Date : 2024-03-11DOI: 10.1038/s41576-024-00696-z
Indhu-Shree Rajan-Babu, Egor Dolzhenko, Michael A. Eberle, Jan M. Friedman
Short tandem repeats (STRs) are a class of repetitive elements, composed of tandem arrays of 1–6 base pair sequence motifs, that comprise a substantial fraction of the human genome. STR expansions can cause a wide range of neurological and neuromuscular conditions, known as repeat expansion disorders, whose age of onset, severity, penetrance and/or clinical phenotype are influenced by the length of the repeats and their sequence composition. The presence of non-canonical motifs, depending on the type, frequency and position within the repeat tract, can alter clinical outcomes by modifying somatic and intergenerational repeat stability, gene expression and mutant transcript-mediated and/or protein-mediated toxicities. Here, we review the diverse structural conformations of repeat expansions, technological advances for the characterization of changes in sequence composition, their clinical correlations and the impact on disease mechanisms. This Review highlights the diversity in sequence composition of disease-related short tandem repeats. The authors discuss how to detect non-canonical motifs in repeat sequences from sequencing data and review the molecular and clinical consequences of sequence composition changes.
{"title":"Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications","authors":"Indhu-Shree Rajan-Babu, Egor Dolzhenko, Michael A. Eberle, Jan M. Friedman","doi":"10.1038/s41576-024-00696-z","DOIUrl":"10.1038/s41576-024-00696-z","url":null,"abstract":"Short tandem repeats (STRs) are a class of repetitive elements, composed of tandem arrays of 1–6 base pair sequence motifs, that comprise a substantial fraction of the human genome. STR expansions can cause a wide range of neurological and neuromuscular conditions, known as repeat expansion disorders, whose age of onset, severity, penetrance and/or clinical phenotype are influenced by the length of the repeats and their sequence composition. The presence of non-canonical motifs, depending on the type, frequency and position within the repeat tract, can alter clinical outcomes by modifying somatic and intergenerational repeat stability, gene expression and mutant transcript-mediated and/or protein-mediated toxicities. Here, we review the diverse structural conformations of repeat expansions, technological advances for the characterization of changes in sequence composition, their clinical correlations and the impact on disease mechanisms. This Review highlights the diversity in sequence composition of disease-related short tandem repeats. The authors discuss how to detect non-canonical motifs in repeat sequences from sequencing data and review the molecular and clinical consequences of sequence composition changes.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":null,"pages":null},"PeriodicalIF":42.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140096929","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}
Pub Date : 2024-03-11DOI: 10.1038/s41576-024-00721-1
Bruce Budowle, Antti Sajantila
Short tandem repeats (STRs), also known as microsatellites, are the primary markers of forensic genetics for developing investigative leads in criminal cases and humanitarian efforts. Their variation in length and sequence provides genetic information even in samples of low quantity and quality, enabling high resolution for identification and attribution purposes, and culminating in the development of national DNA databases. Bruce Budowle and Antti Sajantila reflect on how short tandem repeats (STRs) became the primary markers of forensic genetics, including for developing investigative leads in criminal cases and humanitarian efforts.
短串联重复序列（STR），又称微卫星，是法医遗传学的主要标记，用于开发刑事案件和人道主义工作的调查线索。即使样本数量少、质量差，它们在长度和序列上的变化也能提供遗传信息，从而实现高分辨率的身份识别和归属目的，并最终促成了国家 DNA 数据库的开发。布鲁斯-布道尔（Bruce Budowle）和安蒂-萨扬蒂拉（Antti Sajantila）探讨了短串联重复序列 (STR) 如何成为法医遗传学的主要标记，包括用于开发刑事案件和人道主义工作的调查线索。
{"title":"Short tandem repeats — how microsatellites became the currency of forensic genetics","authors":"Bruce Budowle, Antti Sajantila","doi":"10.1038/s41576-024-00721-1","DOIUrl":"10.1038/s41576-024-00721-1","url":null,"abstract":"Short tandem repeats (STRs), also known as microsatellites, are the primary markers of forensic genetics for developing investigative leads in criminal cases and humanitarian efforts. Their variation in length and sequence provides genetic information even in samples of low quantity and quality, enabling high resolution for identification and attribution purposes, and culminating in the development of national DNA databases. Bruce Budowle and Antti Sajantila reflect on how short tandem repeats (STRs) became the primary markers of forensic genetics, including for developing investigative leads in criminal cases and humanitarian efforts.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":null,"pages":null},"PeriodicalIF":42.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140096899","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}
Pub Date : 2024-03-06DOI: 10.1038/s41576-024-00695-0
Ian Sayers, Catherine John, Jing Chen, Ian P. Hall
Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and interstitial lung diseases are frequently occurring disorders with a polygenic basis that account for a large global burden of morbidity and mortality. Recent large-scale genetic epidemiology studies have identified associations between genetic variation and individual respiratory diseases and linked specific genetic variants to quantitative traits related to lung function. These associations have improved our understanding of the genetic basis and mechanisms underlying common lung diseases. Moreover, examining the overlap between genetic associations of different respiratory conditions, along with evidence for gene–environment interactions, has yielded additional biological insights into affected molecular pathways. This genetic information could inform the assessment of respiratory disease risk and contribute to stratified treatment approaches. In this Review, Sayers et al. summarize findings from recent large-scale genetic epidemiology studies on the genetic underpinnings of chronic respiratory diseases. Furthermore, they outline how insights gained from such studies can improve treatment approaches.
{"title":"Genetics of chronic respiratory disease","authors":"Ian Sayers, Catherine John, Jing Chen, Ian P. Hall","doi":"10.1038/s41576-024-00695-0","DOIUrl":"10.1038/s41576-024-00695-0","url":null,"abstract":"Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and interstitial lung diseases are frequently occurring disorders with a polygenic basis that account for a large global burden of morbidity and mortality. Recent large-scale genetic epidemiology studies have identified associations between genetic variation and individual respiratory diseases and linked specific genetic variants to quantitative traits related to lung function. These associations have improved our understanding of the genetic basis and mechanisms underlying common lung diseases. Moreover, examining the overlap between genetic associations of different respiratory conditions, along with evidence for gene–environment interactions, has yielded additional biological insights into affected molecular pathways. This genetic information could inform the assessment of respiratory disease risk and contribute to stratified treatment approaches. In this Review, Sayers et al. summarize findings from recent large-scale genetic epidemiology studies on the genetic underpinnings of chronic respiratory diseases. Furthermore, they outline how insights gained from such studies can improve treatment approaches.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":null,"pages":null},"PeriodicalIF":39.1,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049949","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}
Pub Date : 2024-03-04DOI: 10.1038/s41576-024-00717-x
Hajk-Georg Drost
Hajk-Georg Drost recalls a 2010 publication that used a phylotranscriptomic approach to estimate the age of genes that contribute to the developmental transcriptome across animal species and inspired a subsequent study on the embryonic hourglass in plants.
{"title":"How ancient genes form animal body plans","authors":"Hajk-Georg Drost","doi":"10.1038/s41576-024-00717-x","DOIUrl":"10.1038/s41576-024-00717-x","url":null,"abstract":"Hajk-Georg Drost recalls a 2010 publication that used a phylotranscriptomic approach to estimate the age of genes that contribute to the developmental transcriptome across animal species and inspired a subsequent study on the embryonic hourglass in plants.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":null,"pages":null},"PeriodicalIF":42.7,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140026592","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}
Pub Date : 2024-03-01DOI: 10.1038/s41576-024-00714-0
Kate E. Galloway
Kate Galloway highlights a paper by Kueh et al., who showed that the cell cycle indirectly influences concentrations of the transcription factor PU.1 to stabilize cell-fate trajectories in mice.
{"title":"Changes in cell-cycle rate drive diverging cell fates","authors":"Kate E. Galloway","doi":"10.1038/s41576-024-00714-0","DOIUrl":"10.1038/s41576-024-00714-0","url":null,"abstract":"Kate Galloway highlights a paper by Kueh et al., who showed that the cell cycle indirectly influences concentrations of the transcription factor PU.1 to stabilize cell-fate trajectories in mice.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":null,"pages":null},"PeriodicalIF":42.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013035","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}
Pub Date : 2024-02-29DOI: 10.1038/s41576-024-00716-y
Hajk-Georg Drost
In this Journal Club, Hajk-Georg Drost highlights a recent study by Pavlopoulos et al. that organizes proteins at tree-of-life scale using massively parallel graph-based clustering.
{"title":"Unveiling the expanding protein universe of life","authors":"Hajk-Georg Drost","doi":"10.1038/s41576-024-00716-y","DOIUrl":"10.1038/s41576-024-00716-y","url":null,"abstract":"In this Journal Club, Hajk-Georg Drost highlights a recent study by Pavlopoulos et al. that organizes proteins at tree-of-life scale using massively parallel graph-based clustering.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":null,"pages":null},"PeriodicalIF":42.7,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996915","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}
Pub Date : 2024-02-29DOI: 10.1038/s41576-024-00693-2
Michela Coan, Simon Haefliger, Samir Ounzain, Rory Johnson
RNA therapeutics (RNATx) aim to treat diseases, including cancer, by targeting or employing RNA molecules for therapeutic purposes. Amongst the most promising targets are long non-coding RNAs (lncRNAs), which regulate oncogenic molecular networks in a cell type-restricted manner. lncRNAs are distinct from protein-coding genes in important ways that increase their therapeutic potential yet also present hurdles to conventional clinical development. Advances in genome editing, oligonucleotide chemistry, multi-omics and RNA engineering are paving the way for efficient and cost-effective lncRNA-focused drug discovery pipelines. In this Review, we present the emerging field of lncRNA therapeutics for oncology, with emphasis on the unique strengths and challenges of lncRNAs within the broader RNATx framework. We outline the necessary steps for lncRNA therapeutics to deliver effective, durable, tolerable and personalized treatments for cancer. Therapeutics that target long non-coding RNAs (lncRNAs) are promising treatments for cancer. In this Review, the authors discuss how technological advances have helped improve drug discovery pipelines for lncRNAs and overview their strengths and challenges as oncological therapeutics.
{"title":"Targeting and engineering long non-coding RNAs for cancer therapy","authors":"Michela Coan, Simon Haefliger, Samir Ounzain, Rory Johnson","doi":"10.1038/s41576-024-00693-2","DOIUrl":"10.1038/s41576-024-00693-2","url":null,"abstract":"RNA therapeutics (RNATx) aim to treat diseases, including cancer, by targeting or employing RNA molecules for therapeutic purposes. Amongst the most promising targets are long non-coding RNAs (lncRNAs), which regulate oncogenic molecular networks in a cell type-restricted manner. lncRNAs are distinct from protein-coding genes in important ways that increase their therapeutic potential yet also present hurdles to conventional clinical development. Advances in genome editing, oligonucleotide chemistry, multi-omics and RNA engineering are paving the way for efficient and cost-effective lncRNA-focused drug discovery pipelines. In this Review, we present the emerging field of lncRNA therapeutics for oncology, with emphasis on the unique strengths and challenges of lncRNAs within the broader RNATx framework. We outline the necessary steps for lncRNA therapeutics to deliver effective, durable, tolerable and personalized treatments for cancer. Therapeutics that target long non-coding RNAs (lncRNAs) are promising treatments for cancer. In this Review, the authors discuss how technological advances have helped improve drug discovery pipelines for lncRNAs and overview their strengths and challenges as oncological therapeutics.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":null,"pages":null},"PeriodicalIF":39.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996914","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}
Pub Date : 2024-02-27DOI: 10.1038/s41576-024-00713-1
Carl G. de Boer
Carl G. de Boer highlights a recent paper by Lim et al. on the importance low-affinity transcription factor-binding sites for determining organismal phenotypes.
Carl G. de Boer 重点介绍了 Lim 等人最近发表的一篇关于低亲和性转录因子结合位点对决定生物表型的重要性的论文。
{"title":"The continuum of transcription factor affinities","authors":"Carl G. de Boer","doi":"10.1038/s41576-024-00713-1","DOIUrl":"10.1038/s41576-024-00713-1","url":null,"abstract":"Carl G. de Boer highlights a recent paper by Lim et al. on the importance low-affinity transcription factor-binding sites for determining organismal phenotypes.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":null,"pages":null},"PeriodicalIF":42.7,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139976934","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}
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