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DOI | 10.1126/science.aay3983 |
Allele-specific open chromatin in human iPSC neurons elucidates functional disease variants | |
Siwei Zhang; Hanwen Zhang; Yifan Zhou; Min Qiao; Siming Zhao; Alena Kozlova; Jianxin Shi; Alan R. Sanders; Gao Wang; Kaixuan Luo; Subhajit Sengupta; Siobhan West; Sheng Qian; Michael Streit; Dimitrios Avramopoulos; Chad A. Cowan; Mengjie Chen; Zhiping P. Pang; Pablo V. Gejman; Xin He; Jubao Duan | |
2020-07-31 | |
发表期刊 | Science
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出版年 | 2020 |
英文摘要 | Genetic variants in noncoding regions of the genome may underlie the development of disease. However, we are just beginning to tease apart the function of such variants associated with neuropsychiatric disease. Using five types of neural progenitor cells derived from 20 human induced pluripotent stem cell lines, Zhang et al. looked at allele-specific open chromatin (ASoC) variants. Many ASoC variants overlapped with genomic elements, such as transcription factor binding sites, and loci identified in genome-wide association studies for neurological traits. From the experimental and computational analyses, they identified single-nucleotide polymorphisms and illuminate how one schizophrenia-associated variant affects neurodevelopment. Science , this issue p. [561][1] Most neuropsychiatric disease risk variants are in noncoding sequences and lack functional interpretation. Because regulatory sequences often reside in open chromatin, we reasoned that neuropsychiatric disease risk variants may affect chromatin accessibility during neurodevelopment. Using human induced pluripotent stem cell (iPSC)–derived neurons that model developing brains, we identified thousands of genetic variants exhibiting allele-specific open chromatin (ASoC). These neuronal ASoCs were partially driven by altered transcription factor binding, overrepresented in brain gene enhancers and expression quantitative trait loci, and frequently associated with distal genes through chromatin contacts. ASoCs were enriched for genetic variants associated with brain disorders, enabling identification of functional schizophrenia risk variants and their cis-target genes. This study highlights ASoC as a functional mechanism of noncoding neuropsychiatric risk variants, providing a powerful framework for identifying disease causal variants and genes. [1]: /lookup/doi/10.1126/science.aay3983 |
领域 | 气候变化 ; 资源环境 |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/286871 |
专题 | 气候变化 资源环境科学 |
推荐引用方式 GB/T 7714 | Siwei Zhang,Hanwen Zhang,Yifan Zhou,et al. Allele-specific open chromatin in human iPSC neurons elucidates functional disease variants[J]. Science,2020. |
APA | Siwei Zhang.,Hanwen Zhang.,Yifan Zhou.,Min Qiao.,Siming Zhao.,...&Jubao Duan.(2020).Allele-specific open chromatin in human iPSC neurons elucidates functional disease variants.Science. |
MLA | Siwei Zhang,et al."Allele-specific open chromatin in human iPSC neurons elucidates functional disease variants".Science (2020). |
条目包含的文件 | 条目无相关文件。 |
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