Cytogenetic Analysis of the Results of Genome Editing on the Cell Model of Parkinson's Disease

Bull Exp Biol Med. 2018 Jul;165(3):378-381. doi: 10.1007/s10517-018-4174-y. Epub 2018 Jul 13.

Abstract

We performed a cytogenetic analysis of the results of CRISPR/Cas9-correction of G2019S mutation in LRRK2 gene associated with Parkinson's disease. Genome editing was performed on induced pluripotent stem cells derived from fibroblasts of a patient carrying this mutation. A mosaic variant of tetraploidy 92 XXYY/46,XY (24-43% cells from various clones) was found in neuronal precursors differentiated from the induced pluripotent stem cells after gene editing procedure. Solitary cases of translocations and chromosome breaks were observed. These data confirm the importance of the development of new approaches ensuring genome stability in CRISPR/Cas9-edited cultures.

Keywords: CRISPR/Cas9; Parkinson’s disease; cytogenetics; genome editing; induced pluripotent stem cells.

Publication types

  • Case Reports

MeSH terms

  • Base Sequence
  • CRISPR-Cas Systems
  • Cell Differentiation
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Gene Editing / methods*
  • Gene Expression
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / pathology
  • Karyotyping
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics*
  • Mosaicism
  • Mutation*
  • Neurons / metabolism*
  • Neurons / pathology
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Primary Cell Culture
  • Tetraploidy

Substances

  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2