Deep Sequencing Analysis of Mitochondrial DNA Heteroplasmy Transmission and the Genetic Bottleneck Effect in Mother-Daughter Pairs

Authors

• Mayyahi Mohammed T. Jaber, Higher Institute of Forensic Sciences, Al Nahrain University, Baghdad, Iraq
• Sarah Talib AL-Mofarji, Higher Institute of Forensic Sciences, Al Nahrain University, Baghdad, Iraq
• Zahraa Mustafa AL-Jumaa, Department of Microbiology, College of Veterinary Medicine, University of Mosul, Mosul, IraqFollow
• Nisred Klichkhanov, Department of Biochemistry, College of Biology, Dagestan State University, Dagestan, Russia

Article Type

Article

Abstract

The inheritance pattern of mitochondrial DNA (mtDNA) from mother to offspring is well known, but the dynamics of heteroplasmy, the coexistence of more than one type of mtDNA molecule per cell, as well as the influence of the Genetic Bottleneck on the Variant Allele Frequency (VAF), are still under active research investigation. This study was conducted with the objective of detecting and analyzing the inheritance pattern of low levels of heteroplasmy across the Whole Mitochondrial Genome (WMS) within 100 phenotypically normal mother-daughter pairs. Blood DNA samples were used for extracting DNA, followed by Whole Mitochondrial Genome Sequencing with a depth of over 1000x. Computer analysis yielded 285 different Single Nucleotide Variants (SNVs), 95 of which were heteroplasmic (VAF < 50%); these were found within the mother's samples. Sixty-three of these heteroplasmic SNVs were found to be transmitted from the mothers to their daughters. What is more important is that there is a strongly statistically significant difference (P < 0.001) between the VAFs of the transmitted heteroplasmic SNVs found within the mothers and their corresponding daughters, with great variability in the VAF values, thus strongly confirming the influence of the Genetic Bottleneck during early embryonic development. The heteroplasmy levels did not correlate statistically significantly with the limited clinical data used (levels of thyroid hormones, glucose, and cholesterol), thus strongly indicating that these heteroplasmy levels are probably physiological heteroplasmy, which are not pathologic. This study confirms the transmission of mtDNA heteroplasmy and the genetic bottleneck effect, highlighting the importance of deep whole-genome sequencing. The study recommends further research focusing on tissue-specific heteroplasmy and the long-term effects of identified variants in clinical settings.

Keywords

Mitochondrial DNA, Heteroplasmy, Whole genome sequencing, Genetic bottleneck, Maternal inheritance

Recommended Citation

Jaber, Mayyahi Mohammed T.; AL-Mofarji, Sarah Talib; AL-Jumaa, Zahraa Mustafa; and Klichkhanov, Nisred (2026) "Deep Sequencing Analysis of Mitochondrial DNA Heteroplasmy Transmission and the Genetic Bottleneck Effect in Mother-Daughter Pairs," Muthanna Medical Journal: Vol. 13: Iss. 3, Article 7.
Available at: https://muthmj.mu.edu.iq/journal/vol13/iss3/7

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.