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Updated summary of genome editing technology in human cultured cells linked to human genetics studies

Authors
  • Miyamoto, Tatsuo1
  • Akutsu, Silvia Natsuko1
  • Matsuura, Shinya1
  • 1 Hiroshima University, Department of Genetics and Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima, Japan , Hiroshima (Japan)
Type
Published Article
Journal
Journal of Human Genetics
Publisher
Springer Nature
Publication Date
Oct 11, 2017
Volume
63
Issue
2
Pages
133–143
Identifiers
DOI: 10.1038/s10038-017-0349-z
Source
Springer Nature
License
Yellow

Abstract

Current deep-sequencing technology provides a mass of nucleotide variations associated with human genetic disorders to accelerate the identification of causative mutations. To understand the etiology of genetic disorders, reverse genetics in human cultured cells is a useful approach for modeling a disease in vitro. However, gene targeting in human cultured cells is difficult because of their low activity of homologous recombination. Engineered endonucleases enable enhancement of the local activation of DNA repair pathways at the human genome target site to rewrite the desired sequence, thereby efficiently generating disease-modeling cultured cell clones. These edited cells can be used to explore the molecular functions of a causative gene product to uncover the etiological mechanisms. The correction of mutations in patient cells using genome editing technology could contribute to the development of unique gene therapies. This technology can also be applied to screening causative mutations. Rare genetic disorders and non-exonic mutation-caused diseases remain frontier in the field of human genetics as it is difficult to validate whether the extracted nucleotide variants are mutation or polymorphism. When isogenic human cultured cells with a candidate variant reproduce the pathogenic phenotypes, it is confirmed that the variant is a causative mutation.

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