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CRISPR/Cas9 increases mitotic gene conversion in human cells
Faculty
Medicine
Year:
2020
Type of Publication:
ZU Hosted
Pages:
Authors:
Lubna Abdel- Aziz AbdelAzim
Staff Zu Site
Abstract In Staff Site
Journal:
Gene Therapy Gene Therapy
Volume:
Keywords :
CRISPR/Cas9 increases mitotic gene conversion , human
Abstract:
Gene conversion is a process of transferring genetic material from one homologous sequence to another. Most reported gene conversions are meiotic although mitotic gene conversion is also described. When using CRISPR/Cas9 to target the human hemoglobin subunit beta (HBB) gene, hemoglobin subunit delta (HBD) gene footprints were observed in HBB gene. However, it is unclear whether these were the results of gene conversion or PCR-mediated sequence shuffling between highly homologous sequences. Here we provide evidence that the HBD footprints in HBB were indeed results of gene conversion. We demonstrated that the CRISPR/Cas9 facilitated unidirectional sequence transfer from the homologous gene without double-strand breaks (DSB) to the one with DSBs, and showed that the rates of HBD footprint in HBB were positively correlated to the HBB insertion and deletion rates. We further showed that when targeting HBD gene, HBB footprints could also be observed in HBD gene. The mitotic gene conversion was observed not only in immortalized HEK293T cells, but also in human primary cells. Our work reveals mitotic gene conversion as an often overlooked effect of CRISPR/Cas9-mediated genome editing.
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Department Related Publications
Fatma Abdelaziz Mossa, "Imipenem resistance and blaimp gene among hospital strains of Pseudomonas aeruginosa at university hospital in Egypt", Journal of Infection in Developing Countries, 2007
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Mei Mohammed Malik Muhammad, "Occurrence of classes I and II integrons in Enterobacteriaceae collected from Zagazig University Hospitals, Egypt", frontier in microbiology, 2015
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Lubna Abdel- Aziz AbdelAzim, "Effect of Vitamin D Adjuvant and Allergen Specific Immunotherapy on Serum IL 10 and IL 17 Levels in Childhood Asthma: A Controlled Clinical Trial", Egyptian Journal of Medical Microbiology, 2021
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Amina Ahmed Mohamed Abdelhady, "Linezolid resistance in coagulase negative Staphylococci isolates and the related genes in intensive care unit patients in a University Hospital in Egypt", Zagazig University, 2023
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Heba Abdel- Aziz Mohammed Abedulaziz, "Diagnostic performance of direct latex agglutination, post-enrichment latex agglutination and culture methods in screening of group B streptococci in late pregnancy: a comparative study", Dove Medical Press Ltd, 2019
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