Multiplex generation and single-cell analysis of structural variants in mammalian genomes

• 成果类型: Article
• 署名作者: Pinglay, Sudarshan; Lalanne, Jean-Benoit; Daza, Riza M.; Kottapalli, Sanjay; Quaisar, Faaiz; Koeppel, Jonas; Garge, Riddhiman K.; Li, Xiaoyi; Lee, David S.; Shendure, Jay
• 署名单位: University of Washington; University of Washington Seattle; Wellcome Trust Sanger Institute; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13028
• DOI: 10.1126/science.ado5978
• 发表日期: 2025-01-31
• 关键词: in-vivo; mouse; deletions; expression; diversity; EVOLUTION; DYNAMICS; IMPACT; loxp; p53

摘要

Studying the functional consequences of structural variants (SVs) in mammalian genomes is challenging because (i) SVs arise much less commonly than single-nucleotide variants or small indels and (ii) methods to generate, map, and characterize SVs in model systems are underdeveloped. To address these challenges, we developed Genome-Shuffle-seq, a method that enables the multiplex generation and mapping of thousands of SVs (deletions, inversions, translocations, and extrachromosomal circles) throughout mammalian genomes. We also demonstrate the co-capture of SV identity with single-cell transcriptomes, facilitating the measurement of SV impact on gene expression. We anticipate that Genome-Shuffle-seq will be broadly useful for the systematic exploration of the functional consequences of SVs on gene expression, the chromatin landscape, and three-dimensional nuclear architecture, while also initiating a path toward a minimal mammalian genome.