BibTex format
@article{Keogh:2018:10.1038/s41467-018-06331-w,
author = {Keogh, M and Wei, W and Aryaman, J and Walker, L and van, den Ameele J and Coxhead, J and Wilson, I and Bashton, M and Beck, J and West, J and Chen, R and Haudenschild, C and Bartha, G and Luo, S and Morris, C and Jones, N and Attems, J and Chinnery, P},
doi = {10.1038/s41467-018-06331-w},
journal = {Nature Communications},
title = {High prevalence of focal and multi-focal somatic genetic variants in the human brain},
url = {http://dx.doi.org/10.1038/s41467-018-06331-w},
volume = {9},
year = {2018}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Somatic mutations during stem cell division are responsible for several cancers. In principle, a similar process could occur during the intense cell proliferation accompanying human brain development, leading to the accumulation of regionally distributed foci of mutations. Using dual platform >5000-fold depth sequencing of 102 genes in 173 adult human brain samples, we detect and validate somatic mutations in 27 of 54 brains. Using a mathematical model of neurodevelopment and approximate Bayesian inference, we predict that macroscopic islands of pathologically mutated neurons are likely to be common in the general population. The detected mutation spectrum also includes DNMT3A and TET2 which are likely to have originated from blood cell lineages. Together, these findings establish developmental mutagenesis as a potential mechanism for neurodegenerative disorders, and provide a novel mechanism for the regional onset and focal pathology in sporadic cases.
AU - Keogh,M
AU - Wei,W
AU - Aryaman,J
AU - Walker,L
AU - van,den Ameele J
AU - Coxhead,J
AU - Wilson,I
AU - Bashton,M
AU - Beck,J
AU - West,J
AU - Chen,R
AU - Haudenschild,C
AU - Bartha,G
AU - Luo,S
AU - Morris,C
AU - Jones,N
AU - Attems,J
AU - Chinnery,P
DO - 10.1038/s41467-018-06331-w
PY - 2018///
SN - 2041-1723
TI - High prevalence of focal and multi-focal somatic genetic variants in the human brain
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/s41467-018-06331-w
UR - http://hdl.handle.net/10044/1/63960
VL - 9
ER -
