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Human brain harbors single nucleotide somatic variations in functionally relevant genes possibly mediated by oxidative stress [version 3; referees: 2 approved]

Authors :
Anchal Sharma
Asgar Hussain Ansari
Renu Kumari
Rajesh Pandey
Rakhshinda Rehman
Bharati Mehani
Binuja Varma
Bapu K. Desiraju
Ulaganathan Mabalirajan
Anurag Agrawal
Arijit Mukhopadhyay
Source :
F1000Research, Vol 5 (2017)
Publication Year :
2017
Publisher :
F1000 Research Ltd, 2017.

Abstract

Somatic variation in DNA can cause cells to deviate from the preordained genomic path in both disease and healthy conditions. Here, using exome sequencing of paired tissue samples, we show that the normal human brain harbors somatic single base variations measuring up to 0.48% of the total variations. Interestingly, about 64% of these somatic variations in the brain are expected to lead to non-synonymous changes, and as much as 87% of these represent G:C>T:A transversion events. Further, the transversion events in the brain were mostly found in the frontal cortex, whereas the corpus callosum from the same individuals harbors the reference genotype. We found a significantly higher amount of 8-OHdG (oxidative stress marker) in the frontal cortex compared to the corpus callosum of the same subjects (pT:A transversions in the cortex. We found significant enrichment for axon guidance and related pathways for genes harbouring somatic variations. This could represent either a directed selection of genetic variations in these pathways or increased susceptibility of some loci towards oxidative stress. This study highlights that oxidative stress possibly influence single nucleotide somatic variations in normal human brain.

Details

Language :
English
ISSN :
20461402
Volume :
5
Database :
Directory of Open Access Journals
Journal :
F1000Research
Publication Type :
Academic Journal
Accession number :
edsdoj.68de2454c7f943c5bfdc7451f23a0ae1
Document Type :
article
Full Text :
https://doi.org/10.12688/f1000research.9495.3