Heteroplasmic Variants of Mitochondrial DNA in Atherosclerotic Lesions of Human Aortic Intima
Abstract
:1. Introduction
2. Materials and Method
2.1. Human Aortic Intimal Tissue Autopsy Samples
2.2. DNA Extraction and mtDNA Enrichment
2.3. Whole mtDNA Sequencing
2.4. Measurement of mtDNA Copy Number
2.5. Bioinformatical and Statistical Analysis of Sequencing Data
- both of two variant nucleotides at the SNP site should be presented in the reads mapped to rCRS;
- the coverage of heteroplasmic site should be within the limit of 0.5–2.0-fold of the mean coverage depth;
- SNPs on homopolymeric sites were excluded from further analysis;
- heteroplasmic site should be covered with forward and reverse reads.
3. Results
3.1. Heteroplasmic Variants of mtDNA
3.2. MtDNA Copy Number
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Case No. (ID) | Age | Gender | Pathologic Diagnosis | The Number of Tissue Samples | ||||
---|---|---|---|---|---|---|---|---|
N | FI | FS | LFP | FP | ||||
as_01 | 85 | f | macrofocal atherosclerosis | 2 | 1 | 2 | 3 | 3 |
as_02 | 83 | m | pulmonary heart disease, thromboembolia of small pulmonary arteries, macrofocal cardiosclerosis | 2 | 2 | 2 | 3 | 3 |
as_03 | 86 | f | pulmonary heart disease, bilateral confluent bronchopneumonia, diffuse microfocal cardiosclerosis | 2 | 2 | 2 | 3 | 3 |
as_04 | 87 | f | pulmonary artery thromboembolia, macrofocal cardiosclerosis | 2 | 3 | 3 | 2 | 2 |
as_05 | 60 | m | gastrorrhagia | 3 | 2 | 2 | 2 | 3 |
as_06 | 83 | m | diffuse microfocal cardiosclerosis, cardiohepatic insufficiency, right-focal abscessed confluent pneumonia | 2 | 2 | 2 | 3 | 3 |
as_07 | 83 | m | right kidney cancer, cancerous cachexia, macrofocal atherosclerosis | 2 | 3 | 2 | 2 | 3 |
Total number of samples | 15 | 15 | 15 | 18 | 20 |
Position | Gene/Region | Nucleotide Change | Mutation Type (for Protein-Coding Genes) and Aminoacid Change | Total Number of Hetero-Plasmy Cases | Mean MAF | SD |
---|---|---|---|---|---|---|
150 | Hypervariable segment 2 | C > T | --- | 2 | 0.0175 | 0.0078 |
152 | Hypervariable segment 2 | T > C | --- | 11 | 0.1528 | 0.0407 |
384 | mt3 H-strand control element | A > G | --- | 1 | 0.0760 | |
1464 | 12S ribosomal RNA | G > A | --- | 1 | 0.1130 | |
1595 | tRNA valine | G > A | --- | 1 | 0.1240 | |
3849 | NADH Dehydrogenase subunit 1 | G > A | syn:L-L | 1 | 0.1050 | |
3915 | NADH Dehydrogenase subunit 1 | G > A | syn:G-G | 2 | 0.0430 | 0.0000 |
4727 | NADH dehydrogenase subunit 2 | A > G | syn:M-M | 1 | 0.0690 | |
7013 | Cytochrome c oxidase subunit I | G > A | syn:T-T | 1 | 0.0540 | |
7076 | Cytochrome c oxidase subunit I | A > G | syn:G-G | 1 | 0.2070 | |
7703 | Cytochrome c oxidase subunit II | T > C | non-syn:Y-H | 3 | 0.1183 | 0.0422 |
8116 | Cytochrome c oxidase subunit II | A > G | syn:G-G | 1 | 0.2730 | |
9935 | Cytochrome c oxidase subunit III | T > C | syn:H-H | 1 | 0.0770 | |
10686 | NADH dehydrogenase subunit 4 | G > A | non-syn:V-M | 1 | 0.0760 | |
11253 | NADH dehydrogenase subunit 4 | T > C | non-syn:I-T | 4 | 0.0398 | 0.0069 |
11711 | NADH dehydrogenase subunit 4 | G > A | non-syn:A-T | 1 | 0.1110 | |
11719 | NADH dehydrogenase subunit 4 | G > A | syn:G-G | 1 | 0.0160 | |
13368 | NADH dehydrogenase subunit 5 | G > A | syn:G-G | 1 | 0.0130 | |
13722 | NADH dehydrogenase subunit 5 | A > G | syn:L-L | 10 | 0.1229 | 0.0453 |
14160 | NADH dehydrogenase subunit 6 | G > A | non-syn:R-W | 1 | 0.0940 | |
15246 | Cytochrome b | G > A | non-syn:G-D | 1 | 0.1140 | |
16092 | Hypervariable segment 1 | T > C | --- | 2 | 0.0410 | 0.0141 |
16126 | Hypervariable segment 1 | T > C | --- | 1 | 0.0170 | |
16129 | Hypervariable segment 1 | G > A | --- | 1 | 0.2170 | |
16294 | Hypervariable segment 1 | C > T | --- | 1 | 0.1160 | |
16304 | Hypervariable segment 1 | T > C | --- | 2 | 0.0395 | 0.0304 |
16482 | Hypervariable segment 1 | A > G | --- | 1 | 0.0570 |
Parameter | The Type of Atherosclerotic Lesion | ||||
---|---|---|---|---|---|
N | FI | FS | LFP | FP | |
The number of minor variants | 68 | 70 | 106 | 113 | 134 |
The number of major variants | 786 | 1049 | 965 | 732 | 801 |
Case No. (ID) | Mean MAF | |
---|---|---|
N+FI | FS+FP+LFP | |
as_01 | 0 | 0.115 |
as_02 | 0.097 | 0.107 |
as_03 | 0.074 | 0.133 |
as_04 | 0.060 | 0.111 |
as_05 | 0.098 | 0.136 |
as_06 | 0.039 | 0.055 |
as_07 | 0.019 | 0.211 |
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Sobenin, I.A.; Zhelankin, A.V.; Khasanova, Z.B.; Sinyov, V.V.; Medvedeva, L.V.; Sagaidak, M.O.; Makeev, V.J.; Kolmychkova, K.I.; Smirnova, A.S.; Sukhorukov, V.N.; et al. Heteroplasmic Variants of Mitochondrial DNA in Atherosclerotic Lesions of Human Aortic Intima. Biomolecules 2019, 9, 455. https://doi.org/10.3390/biom9090455
Sobenin IA, Zhelankin AV, Khasanova ZB, Sinyov VV, Medvedeva LV, Sagaidak MO, Makeev VJ, Kolmychkova KI, Smirnova AS, Sukhorukov VN, et al. Heteroplasmic Variants of Mitochondrial DNA in Atherosclerotic Lesions of Human Aortic Intima. Biomolecules. 2019; 9(9):455. https://doi.org/10.3390/biom9090455
Chicago/Turabian StyleSobenin, Igor A., Andrey V. Zhelankin, Zukhra B. Khasanova, Vasily V. Sinyov, Lyudmila V. Medvedeva, Maria O. Sagaidak, Vsevolod J. Makeev, Kira I. Kolmychkova, Anna S. Smirnova, Vasily N. Sukhorukov, and et al. 2019. "Heteroplasmic Variants of Mitochondrial DNA in Atherosclerotic Lesions of Human Aortic Intima" Biomolecules 9, no. 9: 455. https://doi.org/10.3390/biom9090455