Pub Date : 2024-05-09DOI: 10.1038/s41576-024-00725-x
Pamela Stanley
Glycosylation of proteins and lipids in mammals is essential for embryogenesis and the development of all tissues. Analyses of glycosylation mutants in cultured mammalian cells and model organisms have been key to defining glycosylation pathways and the biological functions of glycans. More recently, applications of genome sequencing have revealed the breadth of rare congenital disorders of glycosylation in humans and the influence of genetics on the synthesis of glycans relevant to infectious diseases, cancer progression and diseases of the immune system. This improved understanding of glycan synthesis and functions is paving the way for advances in the diagnosis and treatment of glycosylation-related diseases, including the development of glycoprotein therapeutics through glycosylation engineering. In this Review, Stanley summarizes the role of genetics in mammalian glycosylation, highlighting how advances in genetic and genomic technologies are helping to characterize the genes involved and contributing to the development of therapies for diseases related to glycosylation.
{"title":"Genetics of glycosylation in mammalian development and disease","authors":"Pamela Stanley","doi":"10.1038/s41576-024-00725-x","DOIUrl":"10.1038/s41576-024-00725-x","url":null,"abstract":"Glycosylation of proteins and lipids in mammals is essential for embryogenesis and the development of all tissues. Analyses of glycosylation mutants in cultured mammalian cells and model organisms have been key to defining glycosylation pathways and the biological functions of glycans. More recently, applications of genome sequencing have revealed the breadth of rare congenital disorders of glycosylation in humans and the influence of genetics on the synthesis of glycans relevant to infectious diseases, cancer progression and diseases of the immune system. This improved understanding of glycan synthesis and functions is paving the way for advances in the diagnosis and treatment of glycosylation-related diseases, including the development of glycoprotein therapeutics through glycosylation engineering. In this Review, Stanley summarizes the role of genetics in mammalian glycosylation, highlighting how advances in genetic and genomic technologies are helping to characterize the genes involved and contributing to the development of therapies for diseases related to glycosylation.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 10","pages":"715-729"},"PeriodicalIF":39.1,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897469","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 : 2024-05-08DOI: 10.1038/s41576-024-00741-x
Kirsty Minton
Logsdon et al. report the second complete sequence of all centromeres from a single human genome, enabling comparative analyses of the variation in tandemly repeating α-satellite DNA.
Logsdon 等人报告了第二个来自单一人类基因组的所有中心粒的完整序列，从而能够对串联重复的 α 卫星 DNA 的变异进行比较分析。
{"title":"Tandem repeat variation of human centromeres","authors":"Kirsty Minton","doi":"10.1038/s41576-024-00741-x","DOIUrl":"10.1038/s41576-024-00741-x","url":null,"abstract":"Logsdon et al. report the second complete sequence of all centromeres from a single human genome, enabling comparative analyses of the variation in tandemly repeating α-satellite DNA.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 7","pages":"455-455"},"PeriodicalIF":42.7,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140881289","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 : 2024-05-07DOI: 10.1038/s41576-024-00736-8
Michael Lamkin, Melissa Gymrek
Tandem repeats are a large source of genetic variation but are challenging to analyse and have been missing from most genome-wide studies. Results now suggest that systematic incorporation of tandem repeats into complex trait analyses is likely to yield a rich source of causal variants and new biological insights. In this Comment, Lamkin and Gymrek discuss recent results that suggest that the systematic incorporation of tandem repeats into complex trait analyses will yield a rich source of causal variants and new biological insights.
{"title":"The emerging role of tandem repeats in complex traits","authors":"Michael Lamkin, Melissa Gymrek","doi":"10.1038/s41576-024-00736-8","DOIUrl":"10.1038/s41576-024-00736-8","url":null,"abstract":"Tandem repeats are a large source of genetic variation but are challenging to analyse and have been missing from most genome-wide studies. Results now suggest that systematic incorporation of tandem repeats into complex trait analyses is likely to yield a rich source of causal variants and new biological insights. In this Comment, Lamkin and Gymrek discuss recent results that suggest that the systematic incorporation of tandem repeats into complex trait analyses will yield a rich source of causal variants and new biological insights.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 7","pages":"452-453"},"PeriodicalIF":42.7,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845112","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 : 2024-04-29DOI: 10.1038/s41576-024-00737-7
Samuel I. Gould
In this Tools of the Trade article, Samuel Gould explains how prime editing sensors can improve experimental efficiency and can be designed using a computational tool he created and named PEGG.
{"title":"Prime editing sensors enable multiplexed genome editing","authors":"Samuel I. Gould","doi":"10.1038/s41576-024-00737-7","DOIUrl":"10.1038/s41576-024-00737-7","url":null,"abstract":"In this Tools of the Trade article, Samuel Gould explains how prime editing sensors can improve experimental efficiency and can be designed using a computational tool he created and named PEGG.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 7","pages":"454-454"},"PeriodicalIF":42.7,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808422","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 : 2024-04-29DOI: 10.1038/s41576-024-00734-w
Kirstyn Brunker
In this Journal Club, Kirstyn Brunker highlights two papers published in 2017 that showcase how the emergence of portable sequencing capabilities improved the real-time response to infectious disease outbreaks on a global scale.
{"title":"Rapid pathogen surveillance: field-ready sequencing solutions","authors":"Kirstyn Brunker","doi":"10.1038/s41576-024-00734-w","DOIUrl":"10.1038/s41576-024-00734-w","url":null,"abstract":"In this Journal Club, Kirstyn Brunker highlights two papers published in 2017 that showcase how the emergence of portable sequencing capabilities improved the real-time response to infectious disease outbreaks on a global scale.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 8","pages":"532-532"},"PeriodicalIF":39.1,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808411","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 : 2024-04-29DOI: 10.1038/s41576-024-00735-9
Renée Beekman
Renée Beekman discusses the possibilities for research into transient enhancers by highlighting a recent paper by Vermunt et al. that identifies how they can modulate gene silencing dynamics.
{"title":"The hidden world of transient enhancers","authors":"Renée Beekman","doi":"10.1038/s41576-024-00735-9","DOIUrl":"10.1038/s41576-024-00735-9","url":null,"abstract":"Renée Beekman discusses the possibilities for research into transient enhancers by highlighting a recent paper by Vermunt et al. that identifies how they can modulate gene silencing dynamics.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 8","pages":"533-533"},"PeriodicalIF":39.1,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808468","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 : 2024-04-24DOI: 10.1038/s41576-024-00733-x
Olivia S. Rissland
In this Journal Club article, Olivia Rissland describes how a 1987 paper by Don Cleveland and colleagues provided insight into co-translational gene regulation of tubulin.
{"title":"What tubulin can teach us about gene regulation","authors":"Olivia S. Rissland","doi":"10.1038/s41576-024-00733-x","DOIUrl":"10.1038/s41576-024-00733-x","url":null,"abstract":"In this Journal Club article, Olivia Rissland describes how a 1987 paper by Don Cleveland and colleagues provided insight into co-translational gene regulation of tubulin.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 8","pages":"531-531"},"PeriodicalIF":39.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639802","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 : 2024-04-24DOI: 10.1038/s41576-024-00720-2
Boshu Li, Chao Sun, Jiayang Li, Caixia Gao
Crop improvement by genome editing involves the targeted alteration of genes to improve plant traits, such as stress tolerance, disease resistance or nutritional content. Techniques for the targeted modification of genomes have evolved from generating random mutations to precise base substitutions, followed by insertions, substitutions and deletions of small DNA fragments, and are finally starting to achieve precision manipulation of large DNA segments. Recent developments in base editing, prime editing and other CRISPR-associated systems have laid a solid technological foundation to enable plant basic research and precise molecular breeding. In this Review, we systematically outline the technological principles underlying precise and targeted genome-modification methods. We also review methods for the delivery of genome-editing reagents in plants and outline emerging crop-breeding strategies based on targeted genome modification. Finally, we consider potential future developments in precise genome-editing technologies, delivery methods and crop-breeding approaches, as well as regulatory policies for genome-editing products. Targeted genome modification using CRISPR–Cas genome editing, base editing or prime editing is driving base research in plants and precise molecular breeding. The authors review the technological principles underlying these methods, approaches for their delivery in plants, and emerging crop-breeding strategies based on targeted genome modification.
通过基因组编辑改良作物涉及有针对性地改变基因，以改善植物的性状，如抗逆性、抗病性或营养成分。对基因组进行定向改造的技术已经从产生随机突变发展到精确的碱基置换，再到小 DNA 片段的插入、置换和删除，最后开始实现对大 DNA 片段的精确操作。碱基编辑、质粒编辑和其他 CRISPR 相关系统的最新发展为植物基础研究和精确分子育种奠定了坚实的技术基础。在本综述中，我们系统地概述了精确和靶向基因组修饰方法的技术原理。我们还回顾了在植物中传递基因组编辑试剂的方法，并概述了基于靶向基因组修饰的新兴作物育种策略。最后，我们考虑了精确基因组编辑技术、传递方法和作物育种方法的未来发展潜力，以及基因组编辑产品的监管政策。
{"title":"Targeted genome-modification tools and their advanced applications in crop breeding","authors":"Boshu Li, Chao Sun, Jiayang Li, Caixia Gao","doi":"10.1038/s41576-024-00720-2","DOIUrl":"10.1038/s41576-024-00720-2","url":null,"abstract":"Crop improvement by genome editing involves the targeted alteration of genes to improve plant traits, such as stress tolerance, disease resistance or nutritional content. Techniques for the targeted modification of genomes have evolved from generating random mutations to precise base substitutions, followed by insertions, substitutions and deletions of small DNA fragments, and are finally starting to achieve precision manipulation of large DNA segments. Recent developments in base editing, prime editing and other CRISPR-associated systems have laid a solid technological foundation to enable plant basic research and precise molecular breeding. In this Review, we systematically outline the technological principles underlying precise and targeted genome-modification methods. We also review methods for the delivery of genome-editing reagents in plants and outline emerging crop-breeding strategies based on targeted genome modification. Finally, we consider potential future developments in precise genome-editing technologies, delivery methods and crop-breeding approaches, as well as regulatory policies for genome-editing products. Targeted genome modification using CRISPR–Cas genome editing, base editing or prime editing is driving base research in plants and precise molecular breeding. The authors review the technological principles underlying these methods, approaches for their delivery in plants, and emerging crop-breeding strategies based on targeted genome modification.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 9","pages":"603-622"},"PeriodicalIF":39.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140642317","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 : 2024-04-22DOI: 10.1038/s41576-024-00718-w
Heng Li, Richard Durbin
Genome sequences largely determine the biology and encode the history of an organism, and de novo assembly — the process of reconstructing the genome sequence of an organism from sequencing reads — has been a central problem in bioinformatics for four decades. Until recently, genomes were typically assembled into fragments of a few megabases at best, but now technological advances in long-read sequencing enable the near-complete assembly of each chromosome — also known as telomere-to-telomere assembly — for many organisms. Here, we review recent progress on assembly algorithms and protocols, with a focus on how to derive near-telomere-to-telomere assemblies. We also discuss the additional developments that will be required to resolve remaining assembly gaps and to assemble non-diploid genomes. In this Review, Li and Durbin discuss how to generate telomere-to-telomere assemblies for large haploid or diploid genomes using currently available data types and algorithms, and outline remaining challenges in resolving highly repetitive sequences and polyploid genomes.
{"title":"Genome assembly in the telomere-to-telomere era","authors":"Heng Li, Richard Durbin","doi":"10.1038/s41576-024-00718-w","DOIUrl":"10.1038/s41576-024-00718-w","url":null,"abstract":"Genome sequences largely determine the biology and encode the history of an organism, and de novo assembly — the process of reconstructing the genome sequence of an organism from sequencing reads — has been a central problem in bioinformatics for four decades. Until recently, genomes were typically assembled into fragments of a few megabases at best, but now technological advances in long-read sequencing enable the near-complete assembly of each chromosome — also known as telomere-to-telomere assembly — for many organisms. Here, we review recent progress on assembly algorithms and protocols, with a focus on how to derive near-telomere-to-telomere assemblies. We also discuss the additional developments that will be required to resolve remaining assembly gaps and to assemble non-diploid genomes. In this Review, Li and Durbin discuss how to generate telomere-to-telomere assemblies for large haploid or diploid genomes using currently available data types and algorithms, and outline remaining challenges in resolving highly repetitive sequences and polyploid genomes.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 9","pages":"658-670"},"PeriodicalIF":39.1,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632363","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 : 2024-04-18DOI: 10.1038/s41576-024-00712-2
Xavier Rambout, Lynne E. Maquat
Proper regulation of mRNA production in the nucleus is critical for the maintenance of cellular homoeostasis during adaptation to internal and environmental cues. Over the past 25 years, it has become clear that the nuclear machineries governing gene transcription, pre-mRNA processing, pre-mRNA and mRNA decay, and mRNA export to the cytoplasm are inextricably linked to control the quality and quantity of mRNAs available for translation. More recently, an ever-expanding diversity of new mechanisms by which nuclear RNA decay factors finely tune the expression of protein-encoding genes have been uncovered. Here, we review the current understanding of how mammalian cells shape their protein-encoding potential by regulating the decay of pre-mRNAs and mRNAs in the nucleus. In this Review, the authors summarize our current understanding of nuclear pre-mRNA and mRNA decay pathways. They describe how aberrantly processed mRNAs are targeted for decay in the nucleus and how this process is regulated to finely control gene expression.
{"title":"Nuclear mRNA decay: regulatory networks that control gene expression","authors":"Xavier Rambout, Lynne E. Maquat","doi":"10.1038/s41576-024-00712-2","DOIUrl":"10.1038/s41576-024-00712-2","url":null,"abstract":"Proper regulation of mRNA production in the nucleus is critical for the maintenance of cellular homoeostasis during adaptation to internal and environmental cues. Over the past 25 years, it has become clear that the nuclear machineries governing gene transcription, pre-mRNA processing, pre-mRNA and mRNA decay, and mRNA export to the cytoplasm are inextricably linked to control the quality and quantity of mRNAs available for translation. More recently, an ever-expanding diversity of new mechanisms by which nuclear RNA decay factors finely tune the expression of protein-encoding genes have been uncovered. Here, we review the current understanding of how mammalian cells shape their protein-encoding potential by regulating the decay of pre-mRNAs and mRNAs in the nucleus. In this Review, the authors summarize our current understanding of nuclear pre-mRNA and mRNA decay pathways. They describe how aberrantly processed mRNAs are targeted for decay in the nucleus and how this process is regulated to finely control gene expression.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 10","pages":"679-697"},"PeriodicalIF":39.1,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140620238","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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