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

Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE

Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-

Single-Cell Analysis*/methods ; Genomic Structural Variation* ; Genome*; Animals ; Humans ; Mice ; Transcriptome ; Chromatin/genetics ; Chromatin/metabolism ; Mammals/genetics

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.

Update of: bioRxiv. 2024 Feb 12:2024.01.22.576756. doi: 10.1101/2024.01.22.576756.. (PMID: 38405830)
Comment in: Science. 2025 Jan 31;387(6733):477-478. doi: 10.1126/science.adt0750.. (PMID: 39883784)

R01 HG010632 United States HG NHGRI NIH HHS

0 (Chromatin)

Date Created: 20250130 Date Completed: 20250130 Latest Revision: 20250315

20250315

10.1126/science.ado5978

39883753