Leija-Salazar, M;
Pittman, A;
Mokretar, K;
Morris, H;
Schapira, AH;
Proukakis, C;
(2020)
Investigation of Somatic Mutations in Human Brains Targeting Genes Associated With Parkinson's Disease.
Frontiers in Neurology
, 11
, Article 570424. 10.3389/fneur.2020.570424.
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Abstract
BACKGROUND: Somatic single nucleotide variant (SNV) mutations occur in neurons but their role in synucleinopathies is unknown. AIM: We aimed to identify disease-relevant low-level somatic SNVs in brains from sporadic patients with synucleinopathies and a monozygotic twin carrying LRRK2 G2019S, whose penetrance could be explained by somatic variation. METHODS AND RESULTS: We included different brain regions from 26 Parkinson's disease (PD), one Incidental Lewy body, three multiple system atrophy cases, and 12 controls. The whole SNCA locus and exons of other genes associated with PD and neurodegeneration were deeply sequenced using molecular barcodes to improve accuracy. We selected 21 variants at 0.33–5% allele frequencies for validation using accurate methods for somatic variant detection. CONCLUSIONS: We could not detect disease-relevant somatic SNVs, however we cannot exclude their presence at earlier stages of degeneration. Our results support that coding somatic SNVs in neurodegeneration are rare, but other types of somatic variants may hold pathological consequences in synucleinopathies.
| Type: | Article |
|---|---|
| Title: | Investigation of Somatic Mutations in Human Brains Targeting Genes Associated With Parkinson's Disease |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fneur.2020.570424 |
| Publisher version: | https://doi.org/10.3389/fneur.2020.570424 |
| Language: | English |
| Additional information: | © 2020 Leija-Salazar, Pittman, Mokretar, Morris, Schapira and Proukakis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Parkinson's disease, SNCA, molecular barcodes, somatic mutation, synuclein, synucleinopathies, targeted sequencing |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10115839 |
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