Postzygotic Somatic Mutations in the Human Brain Expand the Threshold-Liability Model of Schizophrenia.

Frontiers in Psychiatry
Shiva M SinghKathleen A Hill

Abstract

The search for what causes schizophrenia has been onerous. This research has included extensive assessment of a variety of genetic and environmental factors using ever emerging high-resolution technologies and traditional understanding of the biology of the brain. These efforts have identified a large number of schizophrenia-associated genes, some of which are altered by mutational and epi-mutational mechanisms in a threshold liability model of schizophrenia development. The results, however, have limited predictability and the actual cause of the disease remains unknown. This current state asks for conceptualizing the problem differently in light of novel insights into the nature of mutations, the biology of the brain and the fine precision and resolution of emerging technologies. There is mounting evidence that mutations acquired during postzygotic development are more common than germline mutations. Also, the postzygotic somatic mutations including epimutations (PZMs), which often lead to somatic mosaicism, are relatively common in the mammalian brain in comparison to most other tissues and PZMs are more common in patients with neurodevelopmental mental disorders, including schizophrenia. Further, previously inaccessible, de...Continue Reading

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Citations

Feb 26, 2021·Journal of Molecular Evolution·Rama S SinghShiva M Singh

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Methods Mentioned

BETA
single-cell sequencing
methylation aberrations

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