Annual review of genomics and human genetics最新文献_第8页

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

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 8.7 2区生物学

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

A. Wonkam, N. S. Munung, C. Dandara, K. Esoh, N. Hanchard, G. Landouré

{"title":"Five Priorities of African Genomics Research: The Next Frontier.","authors":"A. Wonkam, N. S. Munung, C. Dandara, K. Esoh, N. Hanchard, G. Landouré","doi":"10.1146/annurev-genom-111521-102452","DOIUrl":"https://doi.org/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 global governance frameworks that recognize the ethical implications of data-driven genomic research and empower its application in African social, cultural, economic, and religious contexts. 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":"1 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2022-05-16","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: 9

The Genetics of Brugada Syndrome. Brugada综合征的遗传学。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-05-13 DOI: 10.1146/annurev-genom-112921-011200

M. Cerrone, S. Costa, M. Delmar

{"title":"The Genetics of Brugada Syndrome.","authors":"M. Cerrone, S. Costa, M. Delmar","doi":"10.1146/annurev-genom-112921-011200","DOIUrl":"https://doi.org/10.1146/annurev-genom-112921-011200","url":null,"abstract":"Brugada syndrome is a heritable channelopathy characterized by a peculiar electrocardiogram (ECG) pattern and increased risk of cardiac arrhythmias and sudden death. The arrhythmias originate because of an imbalance between the repolarizing and depolarizing currents that modulate the cardiac action potential. Even if an overt structural cardiomyopathy is not typical of Brugada syndrome, fibrosis and structural changes in the right ventricle contribute to a conduction slowing, which ultimately facilitates ventricular arrhythmias. Currently, Mendelian autosomal dominant transmission is detected in less than 25% of all clinical confirmed cases. Although 23 genes have been associated with the condition, only SCN5A, encoding the cardiac sodium channel, is considered clinically actionable and disease causing. The limited monogenic inheritance has pointed toward new perspectives on the possible complex genetic architecture of the disease, involving polygenic inheritance and a polygenic risk score that can influence penetrance and risk stratification. 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":"465 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75845215","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: 7

A Journey Through Genetics to Biology. 从遗传学到生物学之旅

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-05-13 DOI: 10.1146/annurev-genom-010622-095109

V. van Heyningen

引用次数: 0

Mapping Human Reproduction with Single-Cell Genomics. 用单细胞基因组学绘制人类生殖图谱。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-05-13 DOI: 10.1146/annurev-genom-120121-114415

Magda Marečková, H. Massalha, V. Lorenzi, R. Vento-Tormo

引用次数: 5

Obtaining Complete Human Proteomes. 获得完整的人类蛋白质组。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-04-19 DOI: 10.1146/annurev-genom-112921-024948

Ana Martínez-Val, Ulises H. Guzmán, J. Olsen

{"title":"Obtaining Complete Human Proteomes.","authors":"Ana Martínez-Val, Ulises H. Guzmán, J. Olsen","doi":"10.1146/annurev-genom-112921-024948","DOIUrl":"https://doi.org/10.1146/annurev-genom-112921-024948","url":null,"abstract":"Proteins are the molecular effectors of the information encoded in the genome. Proteomics aims at understanding the molecular functions of proteins in their biological context. In contrast to transcriptomics and genomics, the study of proteomes provides deeper insight into the dynamic regulatory layers encoded at the protein level, such as posttranslational modifications, subcellular localization, cell signaling, and protein-protein interactions. Currently, mass spectrometry (MS)-based proteomics is the technology of choice for studying proteomes at a system-wide scale, contributing to clinical biomarker discovery and fundamental molecular biology. MS technologies are continuously being developed to fulfill the requirements of speed, resolution, and quantitative accuracy, enabling the acquisition of comprehensive proteomes. In this review, we present how MS technology and acquisition methods have evolved to meet the requirements of cutting-edge proteomics research, which is describing the human proteome and its dynamic posttranslational modifications with unprecedented depth. Finally, we provide a perspective on studying proteomes at single-cell resolution. 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":"13 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2022-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78925191","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: 6

Diverse Molecular Mechanisms Underlying Pathogenic Protein Mutations: Beyond the Loss-of-Function Paradigm. 致病蛋白突变背后的多种分子机制:超越功能丧失范式。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2022-04-08 DOI: 10.1146/annurev-genom-111221-103208

Lisa Backwell, J. Marsh

{"title":"Diverse Molecular Mechanisms Underlying Pathogenic Protein Mutations: Beyond the Loss-of-Function Paradigm.","authors":"Lisa Backwell, J. Marsh","doi":"10.1146/annurev-genom-111221-103208","DOIUrl":"https://doi.org/10.1146/annurev-genom-111221-103208","url":null,"abstract":"Most known disease-causing mutations occur in protein-coding regions of DNA. While some of these involve a loss of protein function (e.g., through premature stop codons or missense changes that destabilize protein folding), many act via alternative molecular mechanisms and have dominant-negative or gain-of-function effects. In nearly all cases, these non-loss-of-function mutations can be understood by considering interactions of the wild-type and mutant protein with other molecules, such as proteins, nucleic acids, or small ligands and substrates. Here, we review the diverse molecular mechanisms by which pathogenic mutations can have non-loss-of-function effects, including by disrupting interactions, increasing binding affinity, changing binding specificity, causing assembly-mediated dominant-negative and dominant-positive effects, creating novel interactions, and promoting aggregation and phase separation. We believe that increased awareness of these diverse molecular disease mechanisms will lead to improved diagnosis (and ultimately treatment) of human genetic disorders. 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":"1 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86477953","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: 27

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

IF 8.7 2区生物学

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

C. H. Halbert

{"title":"Equity in Genomic Medicine.","authors":"C. H. Halbert","doi":"10.1146/annurev-genom-112921-022635","DOIUrl":"https://doi.org/10.1146/annurev-genom-112921-022635","url":null,"abstract":"Since the completion of the Human Genome Project, considerable progress has been made in translating knowledge about the genetic basis of disease risk and treatment response into clinical services and public health interventions that have greater precision. It is anticipated that more precision approaches to early detection, prevention, and treatment will be developed and will enhance equity in healthcare and outcomes among disparity populations. Reduced access to genomic medicine research, clinical services, and public health interventions has the potential to exacerbate disparities in genomic medicine. The purpose of this article is to describe these challenges to equity in genomic medicine and identify opportunities and future directions for addressing these issues. Efforts are needed to enhance access to genomic medicine research, clinical services, and public health interventions, and additional research that examines the clinical utility of precision medicine among disparity populations should be prioritized to ensure equity in genomic medicine. 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":"40 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87754217","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