Emerging Topics in Life Sciences最新文献_第3页

Advances in the discovery and analyses of human tandem repeats. 人类串联重复序列的发现和分析进展。

IF 3.8

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230074

Mark J P Chaisson, Arvis Sulovari, Paul N Valdmanis, Danny E Miller, Evan E Eichler

引用次数: 0

Genetic modifiers of repeat expansion disorders. 重复扩增障碍的遗传修饰物。

IF 3.8

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230015

Sangeerthana Rajagopal, Jasmine Donaldson, Michael Flower, Davina J Hensman Moss, Sarah J Tabrizi

{"title":"Genetic modifiers of repeat expansion disorders.","authors":"Sangeerthana Rajagopal, Jasmine Donaldson, Michael Flower, Davina J Hensman Moss, Sarah J Tabrizi","doi":"10.1042/ETLS20230015","DOIUrl":"10.1042/ETLS20230015","url":null,"abstract":"Repeat expansion disorders (REDs) are monogenic diseases caused by a sequence of repetitive DNA expanding above a pathogenic threshold. A common feature of the REDs is a strong genotype-phenotype correlation in which a major determinant of age at onset (AAO) and disease progression is the length of the inherited repeat tract. Over a disease-gene carrier's life, the length of the repeat can expand in somatic cells, through the process of somatic expansion which is hypothesised to drive disease progression. Despite being monogenic, individual REDs are phenotypically variable, and exploring what genetic modifying factors drive this phenotypic variability has illuminated key pathogenic mechanisms that are common to this group of diseases. Disease phenotypes are affected by the cognate gene in which the expansion is found, the location of the repeat sequence in coding or non-coding regions and by the presence of repeat sequence interruptions. Human genetic data, mouse models and in vitro models have implicated the disease-modifying effect of DNA repair pathways via the mechanisms of somatic mutation of the repeat tract. As such, developing an understanding of these pathways in the context of expanded repeats could lead to future disease-modifying therapies for REDs.","PeriodicalId":46394,"journal":{"name":"Emerging Topics in Life Sciences","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49683478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of tandem repeat expansions in brain disorders. 串联重复扩展在脑部疾病中的作用。

IF 3.8

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230022

Mary Anne Panoyan, Frank R Wendt

引用次数: 0

Unravelling the link between neurodevelopmental disorders and short tandem CGG-repeat expansions. 解开神经发育障碍和短串联CGG重复扩增之间的联系。

IF 3.8

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230021

Dale J Annear, R Frank Kooy

{"title":"Unravelling the link between neurodevelopmental disorders and short tandem CGG-repeat expansions.","authors":"Dale J Annear, R Frank Kooy","doi":"10.1042/ETLS20230021","DOIUrl":"10.1042/ETLS20230021","url":null,"abstract":"Neurodevelopmental disorders (NDDs) encompass a diverse group of disorders characterised by impaired cognitive abilities and developmental challenges. Short tandem repeats (STRs), repetitive DNA sequences found throughout the human genome, have emerged as potential contributors to NDDs. Specifically, the CGG trinucleotide repeat has been implicated in a wide range of NDDs, including Fragile X Syndrome (FXS), the most common inherited form of intellectual disability and autism. This review focuses on CGG STR expansions associated with NDDs and their impact on gene expression through repeat expansion-mediated epigenetic silencing. We explore the molecular mechanisms underlying CGG-repeat expansion and the resulting epigenetic modifications, such as DNA hypermethylation and gene silencing. Additionally, we discuss the involvement of other CGG STRs in neurodevelopmental diseases. Several examples, including FMR1, AFF2, AFF3, XYLT1, FRA10AC1, CBL, and DIP2B, highlight the complex relationship between CGG STR expansions and NDDs. Furthermore, recent advancements in this field are highlighted, shedding light on potential future research directions. Understanding the role of STRs, particularly CGG-repeats, in NDDs has the potential to uncover novel diagnostic and therapeutic strategies for these challenging disorders.","PeriodicalId":46394,"journal":{"name":"Emerging Topics in Life Sciences","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41139581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Challenges facing repeat expansion identification, characterisation, and the pathway to discovery. 重复扩展面临的挑战——识别、表征和发现途径。

IF 3.8

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230019

Justin L Read, Kayli C Davies, Genevieve C Thompson, Martin B Delatycki, Paul J Lockhart

{"title":"Challenges facing repeat expansion identification, characterisation, and the pathway to discovery.","authors":"Justin L Read, Kayli C Davies, Genevieve C Thompson, Martin B Delatycki, Paul J Lockhart","doi":"10.1042/ETLS20230019","DOIUrl":"10.1042/ETLS20230019","url":null,"abstract":"Tandem repeat DNA sequences constitute a significant proportion of the human genome. While previously considered to be functionally inert, these sequences are now broadly accepted as important contributors to genetic diversity. However, the polymorphic nature of these sequences can lead to expansion beyond a gene-specific threshold, causing disease. More than 50 pathogenic repeat expansions have been identified to date, many of which have been discovered in the last decade as a result of advances in sequencing technologies and associated bioinformatic tools. Commonly utilised diagnostic platforms including Sanger sequencing, capillary array electrophoresis, and Southern blot are generally low throughput and are often unable to accurately determine repeat size, composition, and epigenetic signature, which are important when characterising repeat expansions. The rapid advances in bioinformatic tools designed specifically to interrogate short-read sequencing and the development of long-read single molecule sequencing is enabling a new generation of high throughput testing for repeat expansion disorders. In this review, we discuss some of the challenges surrounding the identification and characterisation of disease-causing repeat expansions and the technological advances that are poised to translate the promise of genomic medicine to individuals and families affected by these disorders.","PeriodicalId":46394,"journal":{"name":"Emerging Topics in Life Sciences","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54231553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Friedreich's ataxia: new insights. 弗里德里希共济失调症：新见解。

IF 3.8

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230017

Maria M Krasilnikova, Casey L Humphries, Emily M Shinsky

引用次数: 0

Insights into common fragile site instability: DNA replication challenges at DNA repeat sequences. 对常见脆弱位点不稳定性的见解:DNA重复序列的DNA复制挑战。

IF 3.8

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230023

Michal Irony-Tur Sinai, Batsheva Kerem

{"title":"Insights into common fragile site instability: DNA replication challenges at DNA repeat sequences.","authors":"Michal Irony-Tur Sinai, Batsheva Kerem","doi":"10.1042/ETLS20230023","DOIUrl":"10.1042/ETLS20230023","url":null,"abstract":"Common fragile sites (CFS) are specific genomic regions prone to chromosomal instability under conditions of DNA replication stress. CFSs manifest as breaks, gaps, and constrictions on metaphase chromosomes under mild replication stress. These replication-sensitive CFS regions are preferentially unstable during cancer development, as reflected by their association with copy number variants (CNVs) frequently arise in most tumor types. Over the years, it became clear that a combination of different characteristics underlies the enhanced sensitivity of CFSs to replication stress. As of today, there is a strong evidence that the core fragility regions along CFSs overlap with actively transcribed large genes with delayed replication timing upon replication stress. Recently, the mechanistic basis for CFS instability was further extended to regions which span topologically associated domain (TAD) boundaries, generating a fragility signature composed of replication, transcription and genome organization. The presence of difficult-to-replicate AT-rich repeats was one of the early features suggested to characterize a subgroup of CFSs. These long stretches of AT-dinucleotide have the potential to fold into stable secondary structures which may impede replication fork progression, leaving the region under-replicated. Here, we focus on the molecular mechanisms underlying repeat instability at CFSs and on the proteins involved in the resolution of secondary structure impediments arising along repetitive sequence elements which are essential for the maintenance of genome stability.","PeriodicalId":46394,"journal":{"name":"Emerging Topics in Life Sciences","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50159038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Detection and discovery of repeat expansions in ataxia enabled by next-generation sequencing: present and future. 通过下一代测序检测和发现共济失调的重复扩增：现在和未来。

IF 3.8

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230018

Haloom Rafehi, Mark F Bennett, Melanie Bahlo

{"title":"Detection and discovery of repeat expansions in ataxia enabled by next-generation sequencing: present and future.","authors":"Haloom Rafehi, Mark F Bennett, Melanie Bahlo","doi":"10.1042/ETLS20230018","DOIUrl":"10.1042/ETLS20230018","url":null,"abstract":"Hereditary cerebellar ataxias are a heterogenous group of progressive neurological disorders that are disproportionately caused by repeat expansions (REs) of short tandem repeats (STRs). Genetic diagnosis for RE disorders such as ataxias are difficult as the current gold standard for diagnosis is repeat-primed PCR assays or Southern blots, neither of which are scalable nor readily available for all STR loci. In the last five years, significant advances have been made in our ability to detect STRs and REs in short-read sequencing data, especially whole-genome sequencing. Given the increasing reliance of genomics in diagnosis of rare diseases, the use of established RE detection pipelines for RE disorders is now a highly feasible and practical first-step alternative to molecular testing methods. In addition, many new pathogenic REs have been discovered in recent years by utilising WGS data. Collectively, genomes are an important resource/platform for further advancements in both the discovery and diagnosis of REs that cause ataxia and will lead to much needed improvement in diagnostic rates for patients with hereditary ataxia.","PeriodicalId":46394,"journal":{"name":"Emerging Topics in Life Sciences","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endosphere microbial communities and plant nutrient acquisition toward sustainable agriculture. 内圈微生物群落与植物养分获取对可持续农业的影响。

IF 3.8

Emerging Topics in Life Sciences Pub Date : 2023-12-13 DOI: 10.1042/ETLS20230069

Olubukola Oluranti Babalola, Afeez Adesina Adedayo

{"title":"Endosphere microbial communities and plant nutrient acquisition toward sustainable agriculture.","authors":"Olubukola Oluranti Babalola, Afeez Adesina Adedayo","doi":"10.1042/ETLS20230069","DOIUrl":"10.1042/ETLS20230069","url":null,"abstract":"Endophytic microbial communities have essential information for scientists based on their biological contribution to agricultural practices. In the external plant environment, biotic and abiotic factors affect microbial populations before getting into plant tissues. Endophytes are involved in mutualistic and antagonistic activities with the host plant. Microbial communities inhabiting the internal tissues of plant roots depend on their ability to live and contend with other plant microflora. The advantageous ones contribute to soil health and plant growth either directly or indirectly. The microbial communities move via soil-root environment into the endosphere of plants promoting plant growth features like antibiosis, induced systemic resistance, phytohormone synthesis, and bioremediation. Therefore, the existence of these microorganisms contributes to plant genomes, nutrient availability in the soil, the presence of pathogens, and abiotic factors. This review aims at how endophytic microorganisms have displayed great interest in contributing to abundant crop production and phytopathogen inhibition.","PeriodicalId":46394,"journal":{"name":"Emerging Topics in Life Sciences","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136399666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expanding horizons of tandem repeats in biology and medicine: Why 'genomic dark matter' matters. 拓展串联重复序列在生物学和医学中的应用：为什么 "基因组暗物质 "很重要？

IF 3.8

Emerging Topics in Life Sciences Pub Date : 2023-12-13 DOI: 10.1042/ETLS20230075

Anthony J Hannan

{"title":"Expanding horizons of tandem repeats in biology and medicine: Why 'genomic dark matter' matters.","authors":"Anthony J Hannan","doi":"10.1042/ETLS20230075","DOIUrl":"10.1042/ETLS20230075","url":null,"abstract":"Approximately half of the human genome includes repetitive sequences, and these DNA sequences (as well as their transcribed repetitive RNA and translated amino-acid repeat sequences) are known as the repeatome. Within this repeatome there are a couple of million tandem repeats, dispersed throughout the genome. These tandem repeats have been estimated to constitute ∼8% of the entire human genome. These tandem repeats can be located throughout exons, introns and intergenic regions, thus potentially affecting the structure and function of tandemly repetitive DNA, RNA and protein sequences. Over more than three decades, more than 60 monogenic human disorders have been found to be caused by tandem-repeat mutations. These monogenic tandem-repeat disorders include Huntington's disease, a variety of ataxias, amyotrophic lateral sclerosis and frontotemporal dementia, as well as many other neurodegenerative diseases. Furthermore, tandem-repeat disorders can include fragile X syndrome, related fragile X disorders, as well as other neurological and psychiatric disorders. However, these monogenic tandem-repeat disorders, which were discovered via their dominant or recessive modes of inheritance, may represent the 'tip of the iceberg' with respect to tandem-repeat contributions to human disorders. A previous proposal that tandem repeats may contribute to the 'missing heritability' of various common polygenic human disorders has recently been supported by a variety of new evidence. This includes genome-wide studies that associate tandem-repeat mutations with autism, schizophrenia, Parkinson's disease and various types of cancers. In this article, I will discuss how tandem-repeat mutations and polymorphisms could contribute to a wide range of common disorders, along with some of the many major challenges of tandem-repeat biology and medicine. Finally, I will discuss the potential of tandem repeats to be therapeutically targeted, so as to prevent and treat an expanding range of human disorders.","PeriodicalId":46394,"journal":{"name":"Emerging Topics in Life Sciences","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0