Table 2. L, A+B, and D mtDNA haplogroup ARPE-19 cybrids displayed unique SNP variants.
SNP Variants associated with the L, [A+B], and D mtDNA haplogroups were compared to one another. Nucleotide changes containing one or more differences between the studied haplogroups were identified and analyzed. The location of the nucleotide change within the mtDNA, the base pair changed, their associated rs number, their presence in the L, [A+B], or D cybrids, and any associated pathogenesis found in the literature were identified and displayed. Non-synonymous changes present in some but not all haplogroups tested were found at m.4824 A > G, rs ND; m.5178 C > A, rs28357984; m.5442 T > C, rs3020601; m.7146 G > A, rs372136420; m.8701 G > A, rs2000975; m.8794 C > T , rs2298007; m.10398 G > A, rs2853826; and m.13105 G > A, rs2853501. Data was incorporated using http://www.hmtvar.uniba.it as well as http://www.phylotree.org.
| Loci: MT- | SNP | AA Change | rs# | Present in L Cybrids | Present in A+B Cybrids | Present in D Cybrids | Related pathogenesis |
|---|---|---|---|---|---|---|---|
| D-Loop | 152 C>T | Noncoding | rs117135796 | No | Yes | Yes | Predisposition to ataxia, bladder cancer, aging, hepatocellular carcinoma, predisposition to breast cancer, lung cancer, nasopharyngeal carcinoma, stomach cancer, liver cancer, ovarian carcinoma |
| D-Loop | 182 T>C | Noncoding | rs41473347 | No | Yes | Yes | Predisposition to ataxia, bladder cancer, lung cancer |
| D-Loop | 195 C>T | Noncoding | rs2857291 | No | Yes | Yes | Bipolar disease, predisposition to ataxia, bladder cancer, aging, breast cancer, lung cancer |
| D-Loop | 235 A>G | Noncoding | rs3937037 | No | Yes | No | Lung cancer |
| D-Loop | 247 A>G | Noncoding | rs41334645 | No | Yes | Yes | Predisposition to ataxia |
| D-Loop | 263 G>A | Noncoding | rs2853515 | Yes | No | No | Oncocytic adenomas, predisposition to ataxia, breast cancer, nasopharyngeal carcinoma |
| RNR1 | 663 A>G | rRNA | ND | No | Yes | No | Hearing loss |
| RNR1 | 769 A>G | rRNA | rs2853519 | No | Yes | Yes | N/A |
| RNR1 | 825 A>T | rRNA | rs2853520 | No | Yes | Yes | N/A |
| RNR1 | 1018 A>G | rRNA | rs2856982 | No | Yes | Yes | Heteroplasmic variant |
| RNR1 | 1048 C>T | rRNA | rs2000974 | Yes | No | No | Heteroplasmic variant, hearing loss |
| RNR2 | 1736 A>G | rRNA | rs193303006 | No | Yes | No | Heteroplasmic variant |
| RNR2 | 2758 A>G | rRNA | rs2856980 | No | Yes | Yes | N/A |
| RNR2 | 2885 C>T | rRNA | rs2854130 | No | Yes | Yes | N/A |
| ND1 | 3516 C>A | syn:L-L | rs2854132 | Yes | No | No | N/A |
| ND1 | 3594 T>C | syn:V-V | rs193303025 | No | Yes | Yes | Thyroid tumor |
| ND1 | 4104 G>A | syn:L-L | rs1117205 | No | Yes | Yes | N/A |
| ND1 | 4248 T>C | syn:I-I | rs9326618 | No | Yes | No | Homoplasmic variant |
| ND2 | 4824 A>G | non-syn:T-A | ND | No | Yes | No | Glaucoma |
| ND2 | 5178 C>A | non-syn:L-M | rs28357984 | No | No | Yes | Infertility, increased longevity, diabetes, atherosclerosis, hypertension, myocardial infarction, Parkinson’s disease, glaucoma, blood iron metabolism, and cardiovascular disease |
| ND2 | 5442 T>C | non-syn:F-L | rs3020601 | Yes | No | No | Risk of mobility impairment |
| CO1 | 6185 T>C | syn:F-F | rs1029272 | Yes | No | No | Primary Open-Angle Glaucoma (POAG) |
| CO1 | 7146 G>A | non-syn:T-A | rs372136420 | No | Yes | Yes | Asthenospermia |
| CO1 | 7256 T>C | syn:N-N | ND | No | Yes | Yes | N/A |
| TD | 7521 A>G | tRNA | rs200336937 | No | Yes | Yes | Thyroid cancer, colorectal tumor |
| ATP8 | 8468 T>C | syn:L-L | rs1116907 | No | Yes | Yes | N/A |
| ATP6 | 8655 T>C | syn:I-I | rs2853822 | No | Yes | Yes | N/A |
| ATP6 | 8701 G>A | non-syn:T-A | rs2000975 | No | Yes | No | Neuromuscular disorders, somatic lung cancer, thyroid cancer, fertilization failure, atherosclerosis, irritable bowel syndrome, osteosarcoma, MELAS, cardiomyopathy, Parkinson disease, hearing loss |
| ATP6 | 8794 C>T | non-syn:H-Y | rs2298007 | No | Yes | No | Homoplasmic variant, coronary arteriosclerosis, irritable bowel syndrome |
| ATP6 | 9042 C>T | syn:H-H | rs3020605 | Yes | No | No | Homoplasmic variant |
| CO3 | 9347 A>G | syn:L-L | rs2853824 | Yes | No | No | Homoplasmic variant |
| CO3 | 9540 C>T | syn:L-L | rs2248727 | No | Yes | No | Normal-Tension Glaucoma (NTG) |
| ND3 | 10398 G>A | non-syn:T-A | rs2853826 | No | Yes | No | IVF failure, Fuch’s Endothelial Corneal Dystrophy (FECD), breast cancer, esophageal cancer, aging, diabetes, osteoarthritis, schizophrenia, LHON |
| ND4L | 10589 G>A | syn:L-L | rs2853487 | Yes | No | No | Homoplasmic variant |
| ND4L | 10688 A>G | syn:V-V | rs2853488 | No | Yes | Yes | N/A |
| ND4 | 10810 C>T | syn:L-L | rs28358282 | No | Yes | Yes | N/A |
| ND4 | 10873 C>T | syn:P-P | rs2857284 | No | Yes | No | Ischemic stroke |
| ND4 | 12007 G>A | syn:W-W | rs2853497 | Yes | No | No | Homoplasmic variant |
| ND5 | 12705 T>C | syn:I-I | rs193302956 | No | Yes | No | Neuropathy, dystonia, myoclonic epilepsy, MERRF, PD, schizophrenia, bipolar disorder, infantile cardiomyopathy, diabetes, hypertension, AD, Leigh syndrome, blood pressure |
| ND5 | 12720 A>G | syn:M-M | rs2853500 | Yes | No | No | Homoplasmic variant |
| ND5 | 13105 G>A | non-syn:I-V | rs2853501 | No | Yes | Yes | Deafness, neuropathy |
| ND5 | 13506 T>C | syn:Y-Y | rs2857287 | No | Yes | Yes | N/A |
| ND5 | 13650 T>C | syn:P-P | rs2854123 | No | Yes | Yes | N/A |
| CYB | 15301 A>G | syn:L-L | rs193302991 | No | Yes | No | Homoplasmic variant |
| CYB | 15301 G>A | syn:L-L | rs193302991 | No | Yes | Yes | Homoplasmic variant |
| D-Loop | 16129 A>G | Noncoding | rs41534744 | No | Yes | Yes | Ewing’s sarcoma, predisposition to breast cancer, nasopharyngeal carcinoma |
| D-Loop | 16187 T>C | Noncoding | ND | No | Yes | Yes | Friedreich’s ataxia, bladder cancer, lung cancer |
| D-Loop | 16189 T>C | Noncoding | rs28693675 | No | Yes | No | Diabetes mellitus, insulin resistance, cardiomyopathy, hypertension, Friedreich’s ataxia, Ewing’s sarcoma, obesity, predisposition to breast cancer, nasopharyngeal carcinoma |
| D-Loop | 16189 C>T | Noncoding | rs28693675 | No | Yes | Yes | Diabetes mellitus, insulin resistance, cardiomyopathy, hypertension, Friedreich’s ataxia, Ewing’s sarcoma, obesity, predisposition to breast cancer, nasopharyngeal carcinoma |
| D-Loop | 16223 T>C | Noncoding | rs2853513 | No | Yes | No | Mitochondrial disease , predisposition to ataxia, bladder cancer, predisposition to breast cancer, lung cancer, nasopharyngeal carcinoma, stomach cancer, liver cancer |
| D-Loop | 16278 T>C | Noncoding | rs41458645 | No | Yes | Yes | Bladder cancer, predisposition to breast cancer, lung cancer |
| D-Loop | 16290 C>T | Noncoding | ND | No | Yes | No | Parkinson’s disease |
| D-Loop | 16311 C>T | Noncoding | rs34799580 | No | Yes | Yes | Bladder cancer, predisposition to breast cancer, lung cancer |
| D-Loop | 16319 G>A | Noncoding | rs35105996 | No | Yes | No | Homoplasmic variant |
| D-Loop | 16362 T>C | Noncoding | rs62581341 | No | No | Yes | Homoplasmic variant, mitochondrial disease, bladder cancer , predisposition to breast cancer, lung cancer, stomach cancer, liver cancer |
Notes.
ND, Not Determined.
All SNPs had a Quality (A Phred-scaled quality score assigned by the variant caller) Score of 100 and Passed all the Filters.