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Annual review of genomics and human genetics最新文献

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DECIPHER: Improving Genetic Diagnosis Through Dynamic Integration of Genomic and Clinical Data. DECIPHER：通过动态整合基因组和临床数据改进基因诊断。
IF 8.7 2区 生物学
Annual review of genomics and human genetics Pub Date : 2023-08-25 Epub Date: 2023-06-07 DOI: 10.1146/annurev-genom-102822-100509
Julia Foreman, Daniel Perrett, Erica Mazaika, Sarah E Hunt, James S Ware, Helen V Firth
{"title":"DECIPHER: Improving Genetic Diagnosis Through Dynamic Integration of Genomic and Clinical Data.","authors":"Julia Foreman, Daniel Perrett, Erica Mazaika, Sarah E Hunt, James S Ware, Helen V Firth","doi":"10.1146/annurev-genom-102822-100509","DOIUrl":"10.1146/annurev-genom-102822-100509","url":null,"abstract":"<p><p>DECIPHER (<u>D</u>atabas<u>e</u> of Genomi<u>c</u> Var<u>i</u>ation and <u>P</u>henotype in <u>H</u>umans Using <u>E</u>nsembl <u>R</u>esources) shares candidate diagnostic variants and phenotypic data from patients with genetic disorders to facilitate research and improve the diagnosis, management, and therapy of rare diseases. The platform sits at the boundary between genomic research and the clinical community. DECIPHER aims to ensure that the most up-to-date data are made rapidly available within its interpretation interfaces to improve clinical care. Newly integrated cardiac case-control data that provide evidence of gene-disease associations and inform variant interpretation exemplify this mission. New research resources are presented in a format optimized for use by a broad range of professionals supporting the delivery of genomic medicine. The interfaces within DECIPHER integrate and contextualize variant and phenotypic data, helping to determine a robust clinico-molecular diagnosis for rare-disease patients, which combines both variant classification and clinical fit. DECIPHER supports discovery research, connecting individuals within the rare-disease community to pursue hypothesis-driven research.</p>","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"24 ","pages":"151-176"},"PeriodicalIF":8.7,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10298898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","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 p-Arms of Human Acrocentric Chromosomes Play by a Different Set of Rules. 人类顶中心染色体的p臂有一套不同的规则。
IF 8.7 2区 生物学
Annual review of genomics and human genetics Pub Date : 2023-08-25 DOI: 10.1146/annurev-genom-101122-081642
Brian McStay
{"title":"The p-Arms of Human Acrocentric Chromosomes Play by a Different Set of Rules.","authors":"Brian McStay","doi":"10.1146/annurev-genom-101122-081642","DOIUrl":"https://doi.org/10.1146/annurev-genom-101122-081642","url":null,"abstract":"<p><p>The p-arms of the five human acrocentric chromosomes bear nucleolar organizer regions (NORs) comprising ribosomal gene (rDNA) repeats that are organized in a homogeneous tandem array and transcribed in a telomere-to-centromere direction. Precursor ribosomal RNA transcripts are processed and assembled into ribosomal subunits, the nucleolus being the physical manifestation of this process. I review current understanding of nucleolar chromosome biology and describe current exploration into a role for the NOR chromosomal context. Full DNA sequences for acrocentric p-arms are now emerging, aided by the current revolution in long-read sequencing and genome assembly. Acrocentric p-arms vary from 10.1 to 16.7 Mb, accounting for ∼2.2% of the genome. Bordering rDNA arrays, distal junctions, and proximal junctions are shared among the p-arms, with distal junctions showing evidence of functionality. The remaining p-arm sequences comprise multiple satellite DNA classes and segmental duplications that facilitate recombination between heterologous chromosomes, which is likely also involved in Robertsonian translocations.</p>","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"24 ","pages":"63-83"},"PeriodicalIF":8.7,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10152747","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: 5
Methods and Insights from Single-Cell Expression Quantitative Trait Loci. 单细胞表达定量性状基因组的方法和见解。
IF 7.7 2区 生物学
Annual review of genomics and human genetics Pub Date : 2023-08-25 Epub Date: 2023-05-17 DOI: 10.1146/annurev-genom-101422-100437
Joyce B Kang, Alessandro Raveane, Aparna Nathan, Nicole Soranzo, Soumya Raychaudhuri
{"title":"Methods and Insights from Single-Cell Expression Quantitative Trait Loci.","authors":"Joyce B Kang, Alessandro Raveane, Aparna Nathan, Nicole Soranzo, Soumya Raychaudhuri","doi":"10.1146/annurev-genom-101422-100437","DOIUrl":"10.1146/annurev-genom-101422-100437","url":null,"abstract":"<p><p>Recent advancements in single-cell technologies have enabled expression quantitative trait locus (eQTL) analysis across many individuals at single-cell resolution. Compared with bulk RNA sequencing, which averages gene expression across cell types and cell states, single-cell assays capture the transcriptional states of individual cells, including fine-grained, transient, and difficult-to-isolate populations at unprecedented scale and resolution. Single-cell eQTL (sc-eQTL) mapping can identify context-dependent eQTLs that vary with cell states, including some that colocalize with disease variants identified in genome-wide association studies. By uncovering the precise contexts in which these eQTLs act, single-cell approaches can unveil previously hidden regulatory effects and pinpoint important cell states underlying molecular mechanisms of disease. Here, we present an overview of recently deployed experimental designs in sc-eQTL studies. In the process, we consider the influence of study design choices such as cohort, cell states, and ex vivo perturbations. We then discuss current methodologies, modeling approaches, and technical challenges as well as future opportunities and applications.</p>","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"24 ","pages":"277-303"},"PeriodicalIF":7.7,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10784788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10472932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Meiotic Chromosome Structure, the Synaptonemal Complex, and Infertility. 减数分裂染色体结构、突触复合体与不孕症。
IF 8.7 2区 生物学
Annual review of genomics and human genetics Pub Date : 2023-08-25 DOI: 10.1146/annurev-genom-110122-090239
Ian R Adams, Owen R Davies
{"title":"Meiotic Chromosome Structure, the Synaptonemal Complex, and Infertility.","authors":"Ian R Adams,&nbsp;Owen R Davies","doi":"10.1146/annurev-genom-110122-090239","DOIUrl":"https://doi.org/10.1146/annurev-genom-110122-090239","url":null,"abstract":"<p><p>In meiosis, homologous chromosome synapsis is mediated by a supramolecular protein structure, the synaptonemal complex (SC), that assembles between homologous chromosome axes. The mammalian SC comprises at least eight largely coiled-coil proteins that interact and self-assemble to generate a long, zipper-like structure that holds homologous chromosomes in close proximity and promotes the formation of genetic crossovers and accurate meiotic chromosome segregation. In recent years, numerous mutations in human SC genes have been associated with different types of male and female infertility. Here, we integrate structural information on the human SC with mouse and human genetics to describe the molecular mechanisms by which SC mutations can result in human infertility. We outline certain themes in which different SC proteins are susceptible to different types of disease mutation and how genetic variants with seemingly minor effects on SC proteins may act as dominant-negative mutations in which the heterozygous state is pathogenic.</p>","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"24 ","pages":"35-61"},"PeriodicalIF":8.7,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10090339","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: 3
TGF-β and BMP Signaling Pathways in Skeletal Dysplasia with Short and Tall Stature. TGF-β和BMP信号通路在矮个子和高个子骨骼发育不良中的作用。
IF 8.7 2区 生物学
Annual review of genomics and human genetics Pub Date : 2023-08-25 DOI: 10.1146/annurev-genom-120922-094107
Alice Costantini, Alessandra Guasto, Valérie Cormier-Daire
{"title":"TGF-β and BMP Signaling Pathways in Skeletal Dysplasia with Short and Tall Stature.","authors":"Alice Costantini,&nbsp;Alessandra Guasto,&nbsp;Valérie Cormier-Daire","doi":"10.1146/annurev-genom-120922-094107","DOIUrl":"https://doi.org/10.1146/annurev-genom-120922-094107","url":null,"abstract":"<p><p>The transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways play a pivotal role in bone development and skeletal health. More than 30 different types of skeletal dysplasia are now known to be caused by pathogenic variants in genes that belong to the TGF-β superfamily and/or regulate TGF-β/BMP bioavailability. This review describes the latest advances in skeletal dysplasia that is due to impaired TGF-β/BMP signaling and results in short stature (acromelic dysplasia and cardiospondylocarpofacial syndrome) or tall stature (Marfan syndrome). We thoroughly describe the clinical features of the patients, the underlying genetic findings, and the pathomolecular mechanisms leading to disease, which have been investigated mainly using patient-derived skin fibroblasts and mouse models. Although no pharmacological treatment is yet available for skeletal dysplasia due to impaired TGF-β/BMP signaling, in recent years advances in the use of drugs targeting TGF-β have been made, and we also discuss these advances.</p>","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"24 ","pages":"225-253"},"PeriodicalIF":8.7,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10104709","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: 1
Sickle Cell Disease: From Genetics to Curative Approaches. 镰状细胞病:从遗传学到治疗方法。
IF 8.7 2区 生物学
Annual review of genomics and human genetics Pub Date : 2023-08-25 DOI: 10.1146/annurev-genom-120122-081037
Giulia Hardouin, Elisa Magrin, Alice Corsia, Marina Cavazzana, Annarita Miccio, Michaela Semeraro
{"title":"Sickle Cell Disease: From Genetics to Curative Approaches.","authors":"Giulia Hardouin,&nbsp;Elisa Magrin,&nbsp;Alice Corsia,&nbsp;Marina Cavazzana,&nbsp;Annarita Miccio,&nbsp;Michaela Semeraro","doi":"10.1146/annurev-genom-120122-081037","DOIUrl":"https://doi.org/10.1146/annurev-genom-120122-081037","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is a monogenic blood disease caused by a point mutation in the gene coding for β-globin. The abnormal hemoglobin [sickle hemoglobin (HbS)] polymerizes under low-oxygen conditions and causes red blood cells to sickle. The clinical presentation varies from very severe (with acute pain, chronic pain, and early mortality) to normal (few complications and a normal life span). The variability of SCD might be due (in part) to various genetic modulators. First, we review the main genetic factors, polymorphisms, and modifier genes that influence the expression of globin or otherwise modulate the severity of SCD. Considering SCD as a complex, multifactorial disorder is important for the development of appropriate pharmacological and genetic treatments. Second, we review the characteristics, advantages, and disadvantages of the latest advances in gene therapy for SCD, from lentiviral-vector-based approaches to gene-editing strategies.</p>","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"24 ","pages":"255-275"},"PeriodicalIF":8.7,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10104711","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
Return of Results in Genomic Research Using Large-Scale or Whole Genome Sequencing: Toward a New Normal. 大规模或全基因组测序基因组研究结果的回归：迈向新常态。
IF 7.7 2区 生物学
Annual review of genomics and human genetics Pub Date : 2023-08-25 Epub Date: 2023-03-13 DOI: 10.1146/annurev-genom-101122-103209
Susan M Wolf, Robert C Green
{"title":"Return of Results in Genomic Research Using Large-Scale or Whole Genome Sequencing: Toward a New Normal.","authors":"Susan M Wolf, Robert C Green","doi":"10.1146/annurev-genom-101122-103209","DOIUrl":"10.1146/annurev-genom-101122-103209","url":null,"abstract":"<p><p>Genome sequencing is increasingly used in research and integrated into clinical care. In the research domain, large-scale analyses, including whole genome sequencing with variant interpretation and curation, virtually guarantee identification of variants that are pathogenic or likely pathogenic and actionable. Multiple guidelines recommend that findings associated with actionable conditions be offered to research participants in order to demonstrate respect for autonomy, reciprocity, and participant interests in health and privacy. Some recommendations go further and support offering a wider range of findings, including those that are not immediately actionable. In addition, entities covered by the US Health Insurance Portability and Accountability Act (HIPAA) may be required to provide a participant's raw genomic data on request. Despite these widely endorsed guidelines and requirements, the implementation of return of genomic results and data by researchers remains uneven. This article analyzes the ethical and legal foundations for researcher duties to offer adult participants their interpreted results and raw data as the new normal in genomic research.</p>","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"24 ","pages":"393-414"},"PeriodicalIF":7.7,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10237231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Federated Analysis for Privacy-Preserving Data Sharing: A Technical and Legal Primer. 保护隐私数据共享的联合分析：技术与法律入门。
IF 7.7 2区 生物学
Annual review of genomics and human genetics Pub Date : 2023-08-25 Epub Date: 2023-05-30 DOI: 10.1146/annurev-genom-110122-084756
James Casaletto, Alexander Bernier, Robyn McDougall, Melissa S Cline
{"title":"Federated Analysis for Privacy-Preserving Data Sharing: A Technical and Legal Primer.","authors":"James Casaletto, Alexander Bernier, Robyn McDougall, Melissa S Cline","doi":"10.1146/annurev-genom-110122-084756","DOIUrl":"10.1146/annurev-genom-110122-084756","url":null,"abstract":"<p><p>Continued advances in precision medicine rely on the widespread sharing of data that relate human genetic variation to disease. However, data sharing is severely limited by legal, regulatory, and ethical restrictions that safeguard patient privacy. Federated analysis addresses this problem by transferring the code to the data-providing the technical and legal capability to analyze the data within their secure home environment rather than transferring the data to another institution for analysis. This allows researchers to gain new insights from data that cannot be moved, while respecting patient privacy and the data stewards' legal obligations. Because federated analysis is a technical solution to the legal challenges inherent in data sharing, the technology and policy implications must be evaluated together. Here, we summarize the technical approaches to federated analysis and provide a legal analysis of their policy implications.</p>","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"24 ","pages":"347-368"},"PeriodicalIF":7.7,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10846631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10099242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RNA Crossing Membranes: Systems and Mechanisms Contextualizing Extracellular RNA and Cell Surface GlycoRNAs. RNA跨膜:细胞外RNA和细胞表面糖蛋白的系统和机制。
IF 8.7 2区 生物学
Annual review of genomics and human genetics Pub Date : 2023-08-25 DOI: 10.1146/annurev-genom-101722-101224
Peiyuan Chai, Charlotta G Lebedenko, Ryan A Flynn
{"title":"RNA Crossing Membranes: Systems and Mechanisms Contextualizing Extracellular RNA and Cell Surface GlycoRNAs.","authors":"Peiyuan Chai,&nbsp;Charlotta G Lebedenko,&nbsp;Ryan A Flynn","doi":"10.1146/annurev-genom-101722-101224","DOIUrl":"https://doi.org/10.1146/annurev-genom-101722-101224","url":null,"abstract":"<p><p>The subcellular localization of a biopolymer often informs its function. RNA is traditionally confined to the cytosolic and nuclear spaces, where it plays critical and conserved roles across nearly all biochemical processes. Our recent observation of cell surface glycoRNAs may further explain the extracellular role of RNA. While cellular membranes are efficient gatekeepers of charged polymers such as RNAs, a large body of research has demonstrated the accumulation of specific RNA species outside of the cell, termed extracellular RNAs (exRNAs). Across various species and forms of life, protein pores have evolved to transport RNA across membranes, thus providing a mechanistic path for exRNAs to achieve their extracellular topology. Here, we review types of exRNAs and the pores capable of RNA transport to provide a logical and testable path toward understanding the biogenesis and regulation of cell surface glycoRNAs.</p>","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"24 ","pages":"85-107"},"PeriodicalIF":8.7,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10098662","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: 2
Long-Read DNA Sequencing: Recent Advances and Remaining Challenges. 长读DNA测序:最近的进展和仍然存在的挑战。
IF 8.7 2区 生物学
Annual review of genomics and human genetics Pub Date : 2023-08-25 DOI: 10.1146/annurev-genom-101722-103045
Peter E Warburton, Robert P Sebra
{"title":"Long-Read DNA Sequencing: Recent Advances and Remaining Challenges.","authors":"Peter E Warburton,&nbsp;Robert P Sebra","doi":"10.1146/annurev-genom-101722-103045","DOIUrl":"https://doi.org/10.1146/annurev-genom-101722-103045","url":null,"abstract":"<p><p>DNA sequencing has revolutionized medicine over recent decades. However, analysis of large structural variation and repetitive DNA, a hallmark of human genomes, has been limited by short-read technology, with read lengths of 100-300 bp. Long-read sequencing (LRS) permits routine sequencing of human DNA fragments tens to hundreds of kilobase pairs in size, using both real-time sequencing by synthesis and nanopore-based direct electronic sequencing. LRS permits analysis of large structural variation and haplotypic phasing in human genomes and has enabled the discovery and characterization of rare pathogenic structural variants and repeat expansions. It has also recently enabled the assembly of a complete, gapless human genome that includes previously intractable regions, such as highly repetitive centromeres and homologous acrocentric short arms. With the addition of protocols for targeted enrichment, direct epigenetic DNA modification detection, and long-range chromatin profiling, LRS promises to launch a new era of understanding of genetic diversity and pathogenic mutations in human populations.</p>","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"24 ","pages":"109-132"},"PeriodicalIF":8.7,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10099487","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: 4
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