Human brain harbors single nucleotide somatic variations in functionally relevant genes possibly mediated by oxidative stress

Sharma, A; Ansan, AH; Kumari, R; Pandey, R; Rehman, R; Mehani, B; Varma, B; Desiraju, BK; Mabalirajan, U; Agrawal, A; Mukhopadhyay, A

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 (p<0.01), correlating
with the higher G:C>T: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.

Citation

Sharma, A., Ansan, A., Kumari, R., Pandey, R., Rehman, R., Mehani, B., …Mukhopadhyay, A. (2017). Human brain harbors single nucleotide somatic variations in functionally relevant genes possibly mediated by oxidative stress. F1000Research, 5, 2520. https://doi.org/10.12688/f1000research.9495.3

• Journal Article Type: Article
• Online Publication Date: Oct 14, 2016
• Publication Date: Jan 12, 2017
• Deposit Date: Feb 1, 2017
• Publicly Available Date: Feb 1, 2017
• Journal: F1000Research
• Publisher: F1000Research
• Volume: 5
• Pages: 2520
• DOI: https://doi.org/10.12688/f1000research.9495.3
• Publisher URL: http://dx.doi.org/10.12688/f1000research.9495.3
• Related Public URLs: https://f1000research.com/