Aneuploidy and Confined Chromosomal Mosaicism in the Developing Human Brain

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2007 Jun 28

PMID 17593959

Citations 109

Authors

Yuri B Yurov

Ivan Y Iourov

Svetlana G Vorsanova

Thomas Liehr

Alexei D Kolotii

Sergei I Kutsev

Franck Pellestor

Alfia K Beresheva

Irina A Demidova

Viktor S Kravets

Viktor V Monakhov

Ilia V Soloviev

Affiliations

Soon will be listed here.

Abstract

Background: Understanding the mechanisms underlying generation of neuronal variability and complexity remains the central challenge for neuroscience. Structural variation in the neuronal genome is likely to be one important mechanism for neuronal diversity and brain diseases. Large-scale genomic variations due to loss or gain of whole chromosomes (aneuploidy) have been described in cells of the normal and diseased human brain, which are generated from neural stem cells during intrauterine period of life. However, the incidence of aneuploidy in the developing human brain and its impact on the brain development and function are obscure.

Methodology/principal Findings: To address genomic variation during development we surveyed aneuploidy/polyploidy in the human fetal tissues by advanced molecular-cytogenetic techniques at the single-cell level. Here we show that the human developing brain has mosaic nature, being composed of euploid and aneuploid neural cells. Studying over 600,000 neural cells, we have determined the average aneuploidy frequency as 1.25-1.45% per chromosome, with the overall percentage of aneuploidy tending to approach 30-35%. Furthermore, we found that mosaic aneuploidy can be exclusively confined to the brain.

Conclusions/significance: Our data indicates aneuploidization to be an additional pathological mechanism for neuronal genome diversification. These findings highlight the involvement of aneuploidy in the human brain development and suggest an unexpected link between developmental chromosomal instability, intercellural/intertissular genome diversity and human brain diseases.

Citing Articles

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Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress.

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Single-nucleus multi-omic profiling of polyploid heart nuclei identifies fusion-derived cardiomyocytes in the human heart.

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Mapping recurrent mosaic copy number variation in human neurons.

Sun C, Kathuria K, Emery S, Kim B, Burbulis I, Shin J Nat Commun. 2024; 15(1):4220.

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Aneuploidy is Linked to Neurological Phenotypes Through Oxidative Stress.

Islam A, Shaukat Z, Hussain R, Ricos M, Dibbens L, Gregory S J Mol Neurosci. 2024; 74(2):50.

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