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Causes and Consequences of Genome Instability in Psychiatric and Neurodegenerative Diseases

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Abstract—

Each neuron has 100–10000 connections (synapses) with other neural cells, therefore genome pathologies affecting a small proportion of brain cells are capable of causing dysfunction of the entire central nervous system (CNS). Recently, genome and chromosome instability has been uncovered in neurodegeneration (Alzheimer’s disease, ataxia telangiectasia). Somatic tissue-specific mosaicism was observed in the brain of individuals with neuropsychiatric diseases including schizophrenia, autism, intellectual disability, and epilepsy. The study of genetic processes in neurons allows determination of a certain number of genetic pathways and candidate processes, modifications of which can cause impaired genome stability. Brain-specific somatic mutations generally occur at the earliest stages of development. Accordingly, genome variability and somatic mosaicism are expected to be mediated by cell cycle regulation, DNA repair, DNA replication, and programmed cell death in the brain. Endomitosis, endoreduplication, and abortive entrance to the cell cycle are also commonly observed in neurodegeneration. Brain-specific genome instability may be a key element in the pathogenic cascade of neurodegeneration. Here we review the current state of knowledge concerning somatic genome variations in neurodegenerative and psychiatric diseases and analyze the causes and consequences of genomic instability in the CNS.

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Funding

The present study was supported by the Russian Foundation for Basic Research (project no. 19-115-50415 “Expansion”).

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Correspondence to I. Y. Iourov.

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The authors declare no conflict of interest.

The present study contains no data on research involving animals as the objects of the study.

The present study contains no data on research involving humans as the objects of the study.

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Translated by A. Kazantseva

Abbreviations: ASD, autism spectrum disorders; CNS, central nervous system; CIN, chromosome instability; CNV, copy number variations; GIN, genome instability; FISH, fluorescence in situ hybridization; SNP, single nucleotide polymorphism.

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Iourov, I.Y., Vorsanova, S.G., Kurinnaia, O.S. et al. Causes and Consequences of Genome Instability in Psychiatric and Neurodegenerative Diseases. Mol Biol 55, 37–46 (2021). https://doi.org/10.1134/S0026893321010155

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  • DOI: https://doi.org/10.1134/S0026893321010155

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