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MINI-REVIEW: Genome Editing and the Problem of Tetraploidy in Cell Modeling of the Genetic Form of Parkinsonism

V. V. Simonova1, A. S. Vetchinova1, E. V. Novosadova2,a, L. G. Khaspekov1,b, and S. N. Illarioshkin1,c*

1Research Center of Neurology, 125367 Moscow, Russia

2Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia

* To whom correspondence should be addressed.

Received April 19, 2018; Revision received May 8, 2018
The prevalent form of familial parkinsonism is caused by mutations in the LRRK2 gene encoding for the mitochondrial protein kinase. In the review, we discuss possible causes of appearance of tetraploid cells in neuronal precursors obtained from induced pluripotent stem cells from patients with the LRRK2-associated form of parkinsonism after genome editing procedure. As LRRK2 protein participates in cell proliferation and maintenance of the nuclear envelope, spindle fibers, and cytoskeleton, mutations in the LRRK2 gene can affect protein functions and lead, via various mechanisms, to the mitotic machinery disintegration and chromosomal aberration. These abnormalities can appear at different stages of fibroblast reprogramming; therefore, editing of the LRRK2 nucleotide sequence should be done during or before the reprogramming stage.
KEY WORDS: parkinsonism, LRRK2, induced pluripotent stem cells, neuronal precursors, genome editing, tetraploidy

DOI: 10.1134/S0006297918090055