Annual review of genomics and human genetics最新文献_第9页

Mosaicism in Tumor Suppressor Gene Syndromes: Prevalence, Diagnostic Strategies, and Transmission Risk. 肿瘤抑制基因综合征中的镶嵌现象:患病率、诊断策略和传播风险。

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-120121-105450

Jillian L Chen, David T Miller, Laura S Schmidt, David Malkin, Bruce R Korf, Charis Eng, David J Kwiatkowski, Krinio Giannikou

{"title":"Mosaicism in Tumor Suppressor Gene Syndromes: Prevalence, Diagnostic Strategies, and Transmission Risk.","authors":"Jillian L Chen, David T Miller, Laura S Schmidt, David Malkin, Bruce R Korf, Charis Eng, David J Kwiatkowski, Krinio Giannikou","doi":"10.1146/annurev-genom-120121-105450","DOIUrl":"https://doi.org/10.1146/annurev-genom-120121-105450","url":null,"abstract":"A mosaic state arises when pathogenic variants are acquired in certain cell lineages during postzygotic development, and mosaic individuals may present with a generalized or localized phenotype. Here, we review the current state of knowledge regarding mosaicism for eight common tumor suppressor genes-NF1, NF2, TSC1, TSC2, PTEN, VHL, RB1, and TP53-and their related genetic syndromes/entities. We compare and discuss approaches for comprehensive diagnostic genetic testing, the spectrum of variant allele frequency, and disease severity. We also review affected individuals who have no mutation identified after conventional genetic analysis, as well as genotype-phenotype correlations and transmission risk for each tumor suppressor gene in full heterozygous and mosaic patients. This review provides new insight into similarities as well as marked differences regarding the appreciation of mosaicism in these tumor suppressor syndromes.","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":" ","pages":"331-361"},"PeriodicalIF":8.7,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40333597","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

Equity in Genomic Medicine. 基因组医学的公平性。

IF 7.9 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-08-31 Epub Date: 2022-04-01 DOI: 10.1146/annurev-genom-112921-022635

Chanita Hughes Halbert

引用次数: 0

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

The Genetics and Typical Traits of Thoracic Aortic Aneurysm and Dissection. 胸主动脉瘤及夹层的遗传学及典型特征。

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-111521-104455

Jotte Rodrigues Bento, Josephina Meester, Ilse Luyckx, Silke Peeters, Aline Verstraeten, Bart Loeys

引用次数: 9

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 7.9 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":7.9,"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

Five Priorities of African Genomics Research: The Next Frontier. 非洲基因组学研究的五个优先事项：下一个前沿。

IF 7.9 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-08-31 Epub Date: 2022-05-16 DOI: 10.1146/annurev-genom-111521-102452

Ambroise Wonkam, Nchangwi S Munung, Collet Dandara, Kevin K Esoh, Neil A Hanchard, Guida Landoure

{"title":"Five Priorities of African Genomics Research: The Next Frontier.","authors":"Ambroise Wonkam, Nchangwi S Munung, Collet Dandara, Kevin K Esoh, Neil A Hanchard, Guida Landoure","doi":"10.1146/annurev-genom-111521-102452","DOIUrl":"10.1146/annurev-genom-111521-102452","url":null,"abstract":"To embrace the prospects of accurately diagnosing thousands of monogenic conditions, predicting disease risks for complex traits or diseases, tailoring treatment to individuals' pharmacogenetic profiles, and potentially curing some diseases, research into African genomic variation is a scientific imperative. African genomes harbor millions of uncaptured variants accumulated over 300,000 years of modern humans' evolutionary history, with successive waves of admixture, migration, and natural selection combining with extensive ecological diversity to create a broad and exceptional genomic complexity. Harnessing African genomic complexity, therefore, will require sustained commitment and equitable collaboration from the scientific community and funding agencies. African governments must support academic public research and industrial partnerships that build the necessary genetic medicine workforce, utilize the emerging genomic big data to develop expertise in computer science and bioinformatics, and evolve national and globalgovernance frameworks that recognize the ethical implications of data-driven genomic research and empower its application in African social, cultural, economic, and religious contexts.","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"1 1","pages":"499-521"},"PeriodicalIF":7.9,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88635355","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 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