@article{article_1394708, title={HETEROPLASMY-ASSOCIATED MITOCHONDRIAL DNA VARIANTS IN HUMAN BLOOD AND SKELETAL MUSCLE SAMPLES}, journal={Journal of Istanbul Faculty of Medicine}, volume={87}, pages={1–10}, year={2024}, DOI={10.26650/IUITFD.1394708}, author={Güleç, Çağrı and Gedikbaşı, Asuman and Şahin, Gökçen and Toksoy, Güven and Duramaz, Altuğ and Uyguner, Zehra Oya}, keywords={Mitokondriyel heteroplazmi, MT-TL1, MTTL2, MT-RNR2, MT-TM, MT-TI, MT-TF}, abstract={Objective: Mitochondrial heteroplasmy, a recognized trait in eukaryotic cells, plays a pivotal role in complex disorders like mitochondrial diseases. High-throughput sequencing has improved precision in detecting low-level heteroplasmy and can identify ultra-low-level variants (<1%) associated with heteroplasmy attributes. We aimed to investigate potential genetic and demographic factors associated with heteroplasmy levels in mitochondrial variants by analyzing both blood and muscle tissues in individuals, regardless of their phenotypes.
Material and Methods: High-throughput sequencing was conducted on the mitochondrial genomes of 10 individuals, with an equal gender distribution. Variants with heteroplasmy ratios both ranging from 5% to 95% and out of this range were used for statistical analysis.
Result: A total of 194 heteroplasmic variants were identified, of which 13 displayed lower heteroplasmy ratios in both blood and skeletal muscle samples from females, while the mitochondrial control region (D-Loop) exhibited higher ratios.
Conclusion: The study findings confirm the correlation between the m.10398A>G variant and mitochondrial heteroplasmy levels, consistent with prior research. Additionally, we identified the m.1811A>G variant in MT-RNR2 and the m.12308A>G variant in MT-TL2, both associated with higher heteroplasmy. Conversely, the m.582T>C variant in MT-TF, m.3260A>G in MT-TL1, m.3302A>G in MT-TL1, m.4409T>C in MT-TM, and m.4267A>G in MT-TI were linked to lower heteroplasmy, all involving transition-type alterations. Furthermore, our study hinted at a potential age-related threshold for variant accumulation in the control region. Future studies, involving larger cohorts and advanced expression analysis methods, will further contribute to the validation and enhancement of these findings.}, number={1}, publisher={İstanbul Üniversitesi}, organization={This study was supported by the Scientific Research Projects Coordination Unit of Istanbul University, Project No. TYL-2019-33447 and TDK-2018-32544.}