Annual review of genomics and human genetics最新文献_第5页

The UK Biobank: A Shining Example of Genome-Wide Association Study Science with the Power to Detect the Murky Complications of Real-World Epidemiology. 英国生物库：全基因组关联研究科学的光辉典范，有能力检测真实世界流行病学的复杂性。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-08-31 Epub Date: 2022-05-04 DOI: 10.1146/annurev-genom-121321-093606

Vanessa Y Tan, Nicholas J Timpson

{"title":"The UK Biobank: A Shining Example of Genome-Wide Association Study Science with the Power to Detect the Murky Complications of Real-World Epidemiology.","authors":"Vanessa Y Tan, Nicholas J Timpson","doi":"10.1146/annurev-genom-121321-093606","DOIUrl":"10.1146/annurev-genom-121321-093606","url":null,"abstract":"Genome-wide association studies (GWASs) have successfully identified thousands of genetic variants that are reliably associated with human traits. Although GWASs are restricted to certain variant frequencies, they have improved our understanding of the genetic architecture of complex traits and diseases. The UK Biobank (UKBB) has brought substantial analytical opportunity and performance to association studies. The dramatic expansion of many GWAS sample sizes afforded by the inclusion of UKBB data has improved the power of estimation of effect sizes but, critically, has done so in a context where phenotypic depth and precision enable outcome dissection and the application of epidemiological approaches. However, at the same time, the availability of such a large, well-curated, and deeply measured population-based collection has the capacity to increase our exposure to the many complications and inferential complexities associated with GWASs and other analyses. In this review, we discuss the impact that UKBB has had in the GWAS era, some of the opportunities that it brings, and exemplar challenges that illustrate the reality of using data from this world-leading resource.","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"23 ","pages":"569-589"},"PeriodicalIF":8.7,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10271092","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

The Role of Telomeres in Human Disease. 端粒在人类疾病中的作用。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-08-31 DOI: 10.1146/annurev-genom-010422-091101

Mary Armanios

{"title":"The Role of Telomeres in Human Disease.","authors":"Mary Armanios","doi":"10.1146/annurev-genom-010422-091101","DOIUrl":"https://doi.org/10.1146/annurev-genom-010422-091101","url":null,"abstract":"Telomere biology was first studied in maize, ciliates, yeast, and mice, and in recent decades, it has informed understanding of common disease mechanisms with broad implications for patient care. Short telomere syndromes are the most prevalent premature aging disorders, with prominent phenotypes affecting the lung and hematopoietic system. Less understood are a newly recognized group of cancer-prone syndromes that are associated with mutations that lengthen telomeres. A large body of new data from Mendelian genetics and epidemiology now provides an opportunity to reconsider paradigms related to the role of telomeres in human aging and cancer, and in some cases, the findings diverge from what was interpreted from model systems. For example, short telomeres have been considered potent drivers of genome instability, but age-associated solid tumors are rare in individuals with short telomere syndromes, and T cell immunodeficiency explains their spectrum. More commonly, short telomeres promote clonal hematopoiesis, including somatic reversion, providing a new leukemogenesis paradigm that is independent of genome instability. Long telomeres, on the other hand, which extend the cellular life span in vitro, are now appreciated to be the most common shared germline risk factor for cancer in population studies. Through this contemporary lens, I revisit here the role of telomeres in human aging, focusing on how short and long telomeres drive cancer evolution but through distinct mechanisms.","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"23 ","pages":"363-381"},"PeriodicalIF":8.7,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10111244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9312207","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: 29

Extrachromosomal DNA in Cancer. 癌症染色体外DNA。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-08-31 Epub Date: 2022-05-24 DOI: 10.1146/annurev-genom-120821-100535

Vineet Bafna, Paul S Mischel

{"title":"Extrachromosomal DNA in Cancer.","authors":"Vineet Bafna, Paul S Mischel","doi":"10.1146/annurev-genom-120821-100535","DOIUrl":"10.1146/annurev-genom-120821-100535","url":null,"abstract":"In cancer, complex genome rearrangements and other structural alterations, including the amplification of oncogenes on circular extrachromosomal DNA (ecDNA) elements, drive the formation and progression of tumors. ecDNA is a particularly challenging structural alteration. By untethering oncogenes from chromosomal constraints, it elevates oncogene copy number, drives intratumoral genetic heterogeneity, promotes rapid tumor evolution, and results in treatment resistance. The profound changes in DNA shape and nuclear architecture generated by ecDNA alter the transcriptional landscape of tumors by catalyzing new types of regulatory interactions that do not occur on chromosomes. The current suite of tools for interrogating cancer genomes is well suited for deciphering sequence but has limited ability to resolve the complex changes in DNA structure and dynamics that ecDNA generates. Here, we review the challenges of resolving ecDNA form and function and discuss the emerging tool kit for deciphering ecDNA architecture and spatial organization, including what has been learned to date about how this dramatic change in shape alters tumor development, progression, and drug resistance.","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"23 ","pages":"29-52"},"PeriodicalIF":8.7,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10508221/pdf/nihms-1907774.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9701963","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: 10

Advancing Pharmacogenomics from Single-Gene to Preemptive Testing. 推进药物基因组学从单基因到抢先检测。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-08-31 DOI: 10.1146/annurev-genom-111621-102737

Cyrine E Haidar, Kristine R Crews, James M Hoffman, Mary V Relling, Kelly E Caudle

引用次数: 7

Maintaining Transcriptional Specificity Through Mitosis. 通过有丝分裂维持转录特异性。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-08-31 DOI: 10.1146/annurev-genom-121321-094603

Kenji Ito, Kenneth S Zaret

{"title":"Maintaining Transcriptional Specificity Through Mitosis.","authors":"Kenji Ito, Kenneth S Zaret","doi":"10.1146/annurev-genom-121321-094603","DOIUrl":"https://doi.org/10.1146/annurev-genom-121321-094603","url":null,"abstract":"Virtually all cell types have the same DNA, yet each type exhibits its own cell-specific pattern of gene expression. During the brief period of mitosis, the chromosomes exhibit changes in protein composition and modifications, a marked condensation, and a consequent reduction in transcription. Yet as cells exit mitosis, they reactivate their cell-specific programs with high fidelity. Initially, the field focused on the subset of transcription factors that are selectively retained in, and hence bookmark, chromatin in mitosis. However, recent studies show that many transcription factors can be retained in mitotic chromatin and that, surprisingly, such retention can be due to nonspecific chromatin binding. Here, we review the latest studies focusing on low-level transcription via promoters, rather than enhancers, as contributing to mitotic memory, as well as new insights into chromosome structure dynamics, histone modifications, cell cycle signaling, and nuclear envelope proteins that together ensure the fidelity of gene expression through a round of mitosis.","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"23 ","pages":"53-71"},"PeriodicalIF":8.7,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9976632/pdf/nihms-1873036.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10813511","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: 10

Predicting Archaic Hominin Phenotypes from Genomic Data. 从基因组数据预测古人类表型。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-08-31 DOI: 10.1146/annurev-genom-111521-121903

Colin M Brand, Laura L Colbran, John A Capra

引用次数: 7

The Role of Genome Sequencing in Neonatal Intensive Care Units. 基因组测序在新生儿重症监护病房中的作用。

IF 7.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-08-31 Epub Date: 2022-06-08 DOI: 10.1146/annurev-genom-120921-103442

Stephen F Kingsmore, F Sessions Cole

{"title":"The Role of Genome Sequencing in Neonatal Intensive Care Units.","authors":"Stephen F Kingsmore, F Sessions Cole","doi":"10.1146/annurev-genom-120921-103442","DOIUrl":"10.1146/annurev-genom-120921-103442","url":null,"abstract":"Genetic diseases disrupt the functionality of an infant's genome during fetal-neonatal adaptation and represent a leading cause of neonatal and infant mortality in the United States. Due to disease acuity, gene locus and allelic heterogeneity, and overlapping and diverse clinical phenotypes, diagnostic genome sequencing in neonatal intensive care units has required the development of methods to shorten turnaround times and improve genomic interpretation. From 2012 to 2021, 31 clinical studies documented the diagnostic and clinical utility of first-tier rapid or ultrarapid whole-genome sequencing through cost-effective identification of pathogenic genomic variants that change medical management, suggest new therapeutic strategies, and refine prognoses. Genomic diagnosis also permits prediction of reproductive recurrence risk for parents and surviving probands. Using implementation science and quality improvement, deployment of a genomic learning healthcare system will contribute to a reduction of neonatal and infant mortality through the integration of genome sequencing into best-practice neonatal intensive care.","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"23 ","pages":"427-448"},"PeriodicalIF":7.7,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844117/pdf/nihms-1861578.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10528877","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 Joubert-Meckel-Nephronophthisis Spectrum of Ciliopathies. 纤毛病的joubert - meckel -肾病谱。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-08-31 DOI: 10.1146/annurev-genom-121321-093528

Julie C Van De Weghe, Arianna Gomez, Dan Doherty

{"title":"The Joubert-Meckel-Nephronophthisis Spectrum of Ciliopathies.","authors":"Julie C Van De Weghe, Arianna Gomez, Dan Doherty","doi":"10.1146/annurev-genom-121321-093528","DOIUrl":"https://doi.org/10.1146/annurev-genom-121321-093528","url":null,"abstract":"The Joubert syndrome (JS), Meckel syndrome (MKS), and nephronophthisis (NPH) ciliopathy spectrum could be the poster child for advances and challenges in Mendelian human genetics over the past half century. Progress in understanding these conditions illustrates many core concepts of human genetics. The JS phenotype alone is caused by pathogenic variants in more than 40 genes; remarkably, all of the associated proteins function in and around the primary cilium. Primary cilia are near-ubiquitous, microtubule-based organelles that play crucial roles in development and homeostasis. Protruding from the cell, these cellular antennae sense diverse signals and mediate Hedgehog and other critical signaling pathways. Ciliary dysfunction causes many human conditions termed ciliopathies, which range from multiple congenital malformations to adult-onset single-organ failure. Research on the genetics of the JS-MKS-NPH spectrum has spurred extensive functional work exploring the broadly important role of primary cilia in health and disease. This functional work promises to illuminate the mechanisms underlying JS-MKS-NPH in humans, identify therapeutic targets across genetic causes, and generate future precision treatments.","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"23 ","pages":"301-329"},"PeriodicalIF":8.7,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437135/pdf/nihms-1816012.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9751888","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: 12

Establishing the Medical Actionability of Genomic Variants. 建立基因组变异的医学可操作性。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-08-31 DOI: 10.1146/annurev-genom-111021-032401

Katrina A B Goddard, Kristy Lee, Adam H Buchanan, Bradford C Powell, Jessica Ezzell Hunter

{"title":"Establishing the Medical Actionability of Genomic Variants.","authors":"Katrina A B Goddard, Kristy Lee, Adam H Buchanan, Bradford C Powell, Jessica Ezzell Hunter","doi":"10.1146/annurev-genom-111021-032401","DOIUrl":"https://doi.org/10.1146/annurev-genom-111021-032401","url":null,"abstract":"Actionability is an important concept in medicine that does not have a well-accepted standard definition, nor is there a general consensus on how to establish it. Medical actionability is often conflated with clinical utility, a related but distinct concept. This lack of clarity contributes to practice variation and inconsistent coverage decisions in genomic medicine, leading to the potential for systematic bias in the use of evidence-based interventions. We clarify how medical actionability and clinical utility are distinct and then discuss the spectrum of actionability, including benefits for the person, the family, and society. We also describe applications across the life course, including prediction, diagnosis, and treatment. Current challenges in assessing the medical actionability of identified genomic variants include gaps in the evidence, limited contexts with practice guidelines, and subjective aspects of medical actionability. A standardized and authoritative assessment of medical actionability is critical to implementing genomic medicine in a fashion that improves population health outcomes and reduces health disparities.","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"23 ","pages":"173-192"},"PeriodicalIF":8.7,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10184682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9463891","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: 7

Structural Variation in Cancer: Role, Prevalence, and Mechanisms. 癌症的结构变异:作用、流行和机制。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-06-02 DOI: 10.1146/annurev-genom-120121-101149

M. R. Cosenza, Bernardo Rodriguez-Martin, J. Korbel

{"title":"Structural Variation in Cancer: Role, Prevalence, and Mechanisms.","authors":"M. R. Cosenza, Bernardo Rodriguez-Martin, J. Korbel","doi":"10.1146/annurev-genom-120121-101149","DOIUrl":"https://doi.org/10.1146/annurev-genom-120121-101149","url":null,"abstract":"Somatic rearrangements resulting in genomic structural variation drive malignant phenotypes by altering the expression or function of cancer genes. Pan-cancer studies have revealed that structural variants (SVs) are the predominant class of driver mutation in most cancer types, but because they are difficult to discover, they remain understudied when compared with point mutations. This review provides an overview of the current knowledge of somatic SVs, discussing their primary roles, prevalence in different contexts, and mutational mechanisms. SVs arise throughout the life history of cancer, and 55% of driver mutations uncovered by the Pan-Cancer Analysis of Whole Genomes project represent SVs. Leveraging the convergence of cell biology and genomics, we propose a mechanistic classification of somatic SVs, from simple to highly complex DNA rearrangement classes. The actions of DNA repair and DNA replication processes together with mitotic errors result in a rich spectrum of SV formation processes, with cascading effects mediating extensive structural diversity after an initiating DNA lesion has formed. Thanks to new sequencing technologies, including the sequencing of single-cell genomes, open questions about the molecular triggers and the biomolecules involved in SV formation as well as their mutational rates can now be addressed. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 23 is October 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"2 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89511669","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: 19