全息时代:孟德尔染色质病未开发潜力的纽带。

IF 3.8 2区 生物学 Q2 GENETICS & HEREDITY Human Genetics Pub Date : 2024-04-01 Epub Date: 2023-04-28 DOI:10.1007/s00439-023-02560-2
Aileen A Nava, Valerie A Arboleda
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引用次数: 0

摘要

OMICs 级联描述了信息在生物系统中的分级流动。表观基因组位于级联的顶点,从而调节人类基因组的 RNA 和蛋白质表达,并控制着细胞的特性和功能。调控表观基因组的基因被称为表观基因,它们协调着驱动人类发育的复杂生物信号程序。表观基因在人类发育过程中的广泛表达模式意味着,表观基因的致病性种系突变可导致临床上严重的多系统畸形、发育迟缓、智力障碍和干细胞功能障碍。在本综述中,我们把表观基因突变导致的生殖系发育障碍称为 "染色质病"。我们收集了迄今为止数量最多的人类染色质病,我们的扩展方法使已确定的染色质病数量增加了一倍多,达到了由 148 个表基因引起的 179 种疾病。我们的研究显示,20.6%(148/720)的表观基因至少会导致一种染色质病。在这篇综述中,我们重点介绍了将 OMICs 方法应用于染色质病变患者生物样本以确定潜在疾病发病机制的主要实例。快速发展的 OMICs 技术将分子生物学与高通量测序或蛋白质组学相结合,使我们能够剖析出驱动时间、细胞和组织特异性表达的因果机制。利用 OMICs 级联产生的全部数据来研究染色质疾病,将为我们深入了解这些表观基因对发育的影响提供宝贵的信息,并为这些罕见疾病的未来精准靶点指明方向。
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The omics era: a nexus of untapped potential for Mendelian chromatinopathies.

The OMICs cascade describes the hierarchical flow of information through biological systems. The epigenome sits at the apex of the cascade, thereby regulating the RNA and protein expression of the human genome and governs cellular identity and function. Genes that regulate the epigenome, termed epigenes, orchestrate complex biological signaling programs that drive human development. The broad expression patterns of epigenes during human development mean that pathogenic germline mutations in epigenes can lead to clinically significant multi-system malformations, developmental delay, intellectual disabilities, and stem cell dysfunction. In this review, we refer to germline developmental disorders caused by epigene mutation as "chromatinopathies". We curated the largest number of human chromatinopathies to date and our expanded approach more than doubled the number of established chromatinopathies to 179 disorders caused by 148 epigenes. Our study revealed that 20.6% (148/720) of epigenes cause at least one chromatinopathy. In this review, we highlight key examples in which OMICs approaches have been applied to chromatinopathy patient biospecimens to identify underlying disease pathogenesis. The rapidly evolving OMICs technologies that couple molecular biology with high-throughput sequencing or proteomics allow us to dissect out the causal mechanisms driving temporal-, cellular-, and tissue-specific expression. Using the full repertoire of data generated by the OMICs cascade to study chromatinopathies will provide invaluable insight into the developmental impact of these epigenes and point toward future precision targets for these rare disorders.

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来源期刊
Human Genetics
Human Genetics 生物-遗传学
CiteScore
10.80
自引率
3.80%
发文量
94
审稿时长
1 months
期刊介绍: Human Genetics is a monthly journal publishing original and timely articles on all aspects of human genetics. The Journal particularly welcomes articles in the areas of Behavioral genetics, Bioinformatics, Cancer genetics and genomics, Cytogenetics, Developmental genetics, Disease association studies, Dysmorphology, ELSI (ethical, legal and social issues), Evolutionary genetics, Gene expression, Gene structure and organization, Genetics of complex diseases and epistatic interactions, Genetic epidemiology, Genome biology, Genome structure and organization, Genotype-phenotype relationships, Human Genomics, Immunogenetics and genomics, Linkage analysis and genetic mapping, Methods in Statistical Genetics, Molecular diagnostics, Mutation detection and analysis, Neurogenetics, Physical mapping and Population Genetics. Articles reporting animal models relevant to human biology or disease are also welcome. Preference will be given to those articles which address clinically relevant questions or which provide new insights into human biology. Unless reporting entirely novel and unusual aspects of a topic, clinical case reports, cytogenetic case reports, papers on descriptive population genetics, articles dealing with the frequency of polymorphisms or additional mutations within genes in which numerous lesions have already been described, and papers that report meta-analyses of previously published datasets will normally not be accepted. The Journal typically will not consider for publication manuscripts that report merely the isolation, map position, structure, and tissue expression profile of a gene of unknown function unless the gene is of particular interest or is a candidate gene involved in a human trait or disorder.
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