Chromatin accessibility provides a window into the genetic etiology of human brain disease.

IF 13.6 2区 生物学 Q1 GENETICS & HEREDITY
Jaroslav Bendl, John F Fullard, Kiran Girdhar, Pengfei Dong, Roman Kosoy, Biao Zeng, Gabriel E Hoffman, Panos Roussos
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引用次数: 0

Abstract

Neuropsychiatric and neurodegenerative diseases have a significant genetic component. Risk variants often affect the noncoding genome, altering cis-regulatory elements (CREs) and chromatin structure, ultimately impacting gene expression. Chromatin accessibility profiling methods, especially assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), have been used to pinpoint disease-associated SNPs and link them to affected genes and cell types in the brain. The integration of single-cell technologies with genome-wide association studies (GWAS) and transcriptomic data has further advanced our understanding of cell-specific chromatin dynamics. This review discusses recent findings regarding the role played by chromatin accessibility in brain disease, highlighting the need for high-quality data and rigorous computational tools. Future directions include spatial chromatin studies and CRISPR-based functional validation to bridge genetic discovery and clinical applications, paving the way for targeted gene-regulatory therapies.

染色质可及性为人类大脑疾病的遗传病因提供了一个窗口。
神经精神疾病和神经退行性疾病具有重要的遗传成分。风险变异通常影响非编码基因组,改变顺式调控元件(cre)和染色质结构,最终影响基因表达。染色质可及性分析方法,特别是对转座酶可及性染色质的高通量测序(ATAC-seq)测定,已被用于确定疾病相关的snp,并将它们与大脑中受影响的基因和细胞类型联系起来。单细胞技术与全基因组关联研究(GWAS)和转录组学数据的整合进一步提高了我们对细胞特异性染色质动力学的理解。这篇综述讨论了最近关于染色质可及性在脑部疾病中所起作用的发现,强调了对高质量数据和严格计算工具的需求。未来的方向包括空间染色质研究和基于crispr的功能验证,以架起基因发现和临床应用的桥梁,为靶向基因调控治疗铺平道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Trends in Genetics
Trends in Genetics 生物-遗传学
CiteScore
20.90
自引率
0.90%
发文量
160
审稿时长
6-12 weeks
期刊介绍: Launched in 1985, Trends in Genetics swiftly established itself as a "must-read" for geneticists, offering concise, accessible articles covering a spectrum of topics from developmental biology to evolution. This reputation endures, making TiG a cherished resource in the genetic research community. While evolving with the field, the journal now embraces new areas like genomics, epigenetics, and computational genetics, alongside its continued coverage of traditional subjects such as transcriptional regulation, population genetics, and chromosome biology. Despite expanding its scope, the core objective of TiG remains steadfast: to furnish researchers and students with high-quality, innovative reviews, commentaries, and discussions, fostering an appreciation for advances in genetic research. Each issue of TiG presents lively and up-to-date Reviews and Opinions, alongside shorter articles like Science & Society and Spotlight pieces. Invited from leading researchers, Reviews objectively chronicle recent developments, Opinions provide a forum for debate and hypothesis, and shorter articles explore the intersection of genetics with science and policy, as well as emerging ideas in the field. All articles undergo rigorous peer-review.
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