Most genome editing analyses to date are based on quantifying small insertions and deletions. Here, we show that CRISPR-Cas9 genome editing can induce large gene modifications, such as deletions, insertions, and complex local rearrangements in different primary cells and cell lines. We analyzed large deletion events in hematopoietic stem and progenitor cells (HSPCs) using different methods, including clonal genotyping, droplet digital polymerase chain reaction, single-molecule real-time sequencing with unique molecular identifier, and long-amplicon sequencing assay. Our results show that large deletions of up to several thousand bases occur with high frequencies at the Cas9 on-target cut sites on the
HBB
(11.7 to 35.4%),
HBG
(14.3%), and
BCL11A
(13.2%) genes in HSPCs and the
PD-1
(15.2%) gene in T cells. Our findings have important implications to advancing genome editing technologies for treating human diseases, because unintended large gene modifications may persist, thus altering the biological functions and reducing the available therapeutic alleles.
The deformation characteristics and instability patterns of rotational landslides are complicated. Such landslides are large and occur continuously, seriously threatening people’s lives. We used interferometry synthetic aperture radar (InSAR), digital elevation models of difference (DODs), numerical simulations, and other techniques for analyzing the topographic changes, surface deformation and movement process before, during and after a landslide. Based on the high-resolution terrain data before and after the landslide, the topographic changes were analyzed, and the active zone of the landslide was identified. The areas of the topographic changes were mainly located on the main scarp, toe and secondary landslides. The topographic changes were influenced by rainfall and rill erosion. The geomorphologically-guided InSAR interpretation method was applied to explore the displacement pattern. The deformation area in the middle of the landslide coincided with the secondary landslides. A time-series InSAR analysis revealed the dynamic evolution of the deformation before and after the landslide. Based on its evolution, the simulated landslide process included the main landslide and three secondary landslides. Based on the displacement of the longitudinal ground surface profiles, the displacement characteristics and kinematic behavior were summarized and compared with those of a single rotational landslide and multiple rotational landslides. The single rotational landslide had obvious secondary and progressive characteristics, developing into multiple rotational landslides triggered by conditions such as rainfall.
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