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Genome Editing and the Problem of Tetraploidy in Cell Modeling of the Genetic Form of Parkinsonism

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Abstract

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.

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Abbreviations

ATM:

ataxia telangiectasia mutated

iPSCs:

induced pluripotent stem cells

PD:

Parkinson’s disease

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Authors and Affiliations

  1. Research Center of Neurology, 125367, Moscow, Russia

    V. V. Simonova, A. S. Vetchinova, L. G. Khaspekov & S. N. Illarioshkin

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

    E. V. Novosadova

Authors
  1. V. V. Simonova
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  2. A. S. Vetchinova
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  3. E. V. Novosadova
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  4. L. G. Khaspekov
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  5. S. N. Illarioshkin
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Correspondence to S. N. Illarioshkin.

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Original Russian Text © V. V. Simonova, A. S. Vetchinova, E. V. Novosadova, L. G. Khaspekov, S. N. Illarioshkin, 2018, published in Biokhimiya, 2018, Vol. 83, No. 9, pp. 1311–1317.

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Simonova, V.V., Vetchinova, A.S., Novosadova, E.V. et al. Genome Editing and the Problem of Tetraploidy in Cell Modeling of the Genetic Form of Parkinsonism. Biochemistry Moscow 83, 1040–1045 (2018). https://doi.org/10.1134/S0006297918090055

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