Mitochondrial DNA point mutations and relative copy number in 1363 disease and control human brains
Wei W, Keogh MJ, Wilson I, Coxhead J, Ryan S, Rollinson S, Griffin H, Kurzawa-Akanbi M et al.. Acta neuropathologica communications, 2017-02-02
Topic: Brain proteins, microglia and lab models
Mitochondria play a key role in common neurodegenerative diseases and contain their own genome: mtDNA. Common inherited polymorphic variants of mtDNA have been associated with several neurodegenerative diseases, and somatic deletions of mtDNA have been found in affected brain regions. However, there are conflicting reports describing the role of rare inherited variants and somatic point mutations in neurodegenerative disorders, and recent evidence also implicates mtDNA levels. To address these issues we studied 1363 post mortem human brains with a histopathological diagnosis of Parkinson's disease (PD), Alzheimer's disease (AD), Frontotemporal dementia - Amyotrophic Lateral Sclerosis (FTD-ALS), Creutzfeldt Jacob disease (CJD), and healthy controls. We obtained high-depth whole mitochondrial genome sequences using off target reads from whole exome sequencing to determine the association of mtDNA variation with the development and progression of disease, and to better understand the development of mtDNA mutations and copy number in the aging brain. With this approach, we found a surprisingly high frequency of heteroplasmic mtDNA variants in 32.3% of subjects. However, we found no evidence of an association between rare inherited variants of mtDNA or mtDNA heteroplasmy and disease. In contrast, we observed a reduction in the amount of mtDNA copy in both AD and CJD. Based on these findings, single nucleotide variants of mtDNA are unlikely to play a major role in the pathogenesis of these neurodegenerative diseases, but mtDNA levels merit further investigation.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Wei, W., Keogh, M. J., Wilson, I., Coxhead, J., Ryan, S., Rollinson, S., et al. (2017). Mitochondrial DNA point mutations and relative copy number in 1363 disease and control human brains. Acta neuropathologica communications. https://doi.org/10.1186/s40478-016-0404-6
Vancouver
Wei W, Keogh MJ, Wilson I, Coxhead J, Ryan S, Rollinson S, et al. Mitochondrial DNA point mutations and relative copy number in 1363 disease and control human brains. Acta neuropathologica communications. 2017. doi:10.1186/s40478-016-0404-6. PMID: 28153046.
BibTeX
@article{wei2017-28153046,
author = {Wei, W. and Keogh, M. J. and Wilson, I. and Coxhead, J. and Ryan, S. and Rollinson, S. and Griffin, H. and Kurzawa-Akanbi, M. and others},
title = {{Mitochondrial DNA point mutations and relative copy number in 1363 disease and control human brains}},
journal = {Acta neuropathologica communications},
year = {2017},
doi = {10.1186/s40478-016-0404-6},
pmid = {28153046},
url = {https://doi.org/10.1186/s40478-016-0404-6}
}
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Key findings
- Common inherited polymorphic variants of mtDNA have been associated with several neurodegenerative diseases, and somatic deletions of mtDNA have been found in affected brain regions.
- With this approach, we found a surprisingly high frequency of heteroplasmic mtDNA variants in 32.3% of subjects.
- However, we found no evidence of an association between rare inherited variants of mtDNA or mtDNA heteroplasmy and disease.
- In contrast, we observed a reduction in the amount of mtDNA copy in both AD and CJD.
- Based on these findings, single nucleotide variants of mtDNA are unlikely to play a major role in the pathogenesis of these neurodegenerative diseases, but mtDNA levels merit further investigation.
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Study details
- Participants1,363
- Effect size32.3%
- Evidence strengthLow
How this study scored 55/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 32 of the 58 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,363 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28153046) |
| Free to read | 2 / 2 | Free to read |
| Points | 32 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 32 of the 58 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
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