Annual review of genomics and human genetics最新文献_第10页

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

Investigating the Potential Roles of SINEs in the Human Genome. 研究正弦函数在人类基因组中的潜在作用。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2021-08-31 Epub Date: 2021-04-01 DOI: 10.1146/annurev-genom-111620-100736

Xiao-Ou Zhang, Henry Pratt, Zhiping Weng

引用次数: 14

Global Governance of Human Genome Editing: What Are the Rules? 人类基因组编辑的全球治理:规则是什么?

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2021-08-31 Epub Date: 2021-03-05 DOI: 10.1146/annurev-genom-111320-091930

Gary E Marchant

{"title":"Global Governance of Human Genome Editing: What Are the Rules?","authors":"Gary E Marchant","doi":"10.1146/annurev-genom-111320-091930","DOIUrl":"https://doi.org/10.1146/annurev-genom-111320-091930","url":null,"abstract":"Human gene editing, particularly using the new CRISPR/Cas9 technology, will greatly increase the capability to make precise changes to human genomes. Human gene editing can be broken into four major categories: somatic therapy, heritable gene editing, genetic enhancement, and basic and applied research. Somatic therapy is generally well governed by national regulatory systems, so the need for global governance is less urgent. All nations are in agreement that heritable gene editing should not proceed at this time, but there is likely to be divergence if and when such procedures are shown to be safe and effective. Gene editing for enhancement purposes is not feasible today but is more controversial with the public, and many nations do not have well-developed regulatory systems for addressing genetic enhancement. Finally, different nations treat research with human embryos very differently based on deeply embedded social, cultural, ethical, and legal traditions. Several international governance mechanisms are currently in operation for human gene editing, and several other governance mechanisms have been proposed. It is unlikely that any single mechanism will alone be effective for governing human gene editing; rather, a polycentric or ecosystem approach that includes several overlapping and interacting components is likely to be necessary.","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"22 ","pages":"385-405"},"PeriodicalIF":8.7,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25433231","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

Brain Somatic Mutation in Aging and Alzheimer's Disease. 衰老和阿尔茨海默病中的大脑体细胞突变。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2021-08-31 Epub Date: 2021-05-12 DOI: 10.1146/annurev-genom-121520-081242

Michael B Miller, Hannah C Reed, Christopher A Walsh

引用次数: 27

The Science and Art of Clinical Genetic Variant Classification and Its Impact on Test Accuracy. 临床遗传变异分类的科学与艺术及其对检测准确性的影响。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2021-08-31 Epub Date: 2021-04-26 DOI: 10.1146/annurev-genom-121620-082709

Hunter H Giles, Madhuri R Hegde, Elaine Lyon, Christine M Stanley, Iain D Kerr, Megan E Garlapow, Julie M Eggington

{"title":"The Science and Art of Clinical Genetic Variant Classification and Its Impact on Test Accuracy.","authors":"Hunter H Giles, Madhuri R Hegde, Elaine Lyon, Christine M Stanley, Iain D Kerr, Megan E Garlapow, Julie M Eggington","doi":"10.1146/annurev-genom-121620-082709","DOIUrl":"https://doi.org/10.1146/annurev-genom-121620-082709","url":null,"abstract":"Clinical genetic variant classification science is a growing subspecialty of clinical genetics and genomics. The field's continued improvement is essential for the success of precision medicine in both germline (hereditary) and somatic (oncology) contexts. This review focuses on variant classification for DNA next-generation sequencing tests. We first summarize current limitations in variant discovery and definition, and then describe the current five- and four-tier classification systems outlined in dominant standards and guideline publications for germline and somatic tests, respectively. We then discuss measures of variant classification discordance and the field's bias for positive results, as well as considerations for panel size and population screening in the context of estimates of positive predictive value thatincorporate estimated variant classification imperfections. Finally, we share opinions on the current state of variant classification from some of the authors of the most widely used standards and guideline publications and from other domain experts.","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"22 ","pages":"285-307"},"PeriodicalIF":8.7,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38908602","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

Transcriptional Regulation by (Super)Enhancers: From Discovery to Mechanisms. (超级)增强子的转录调控:从发现到机制。

IF 8.7 2区生物学

Annual review of genomics and human genetics Pub Date : 2021-08-31 Epub Date: 2021-05-05 DOI: 10.1146/annurev-genom-122220-093818

Frank Grosveld, Jente van Staalduinen, Ralph Stadhouders

引用次数: 49