mtDNA Heteroplasmy in Monozygotic Twins Discordant for Schizophrenia
Although monozygotic (MZ) twins have theoretically identical nuclear DNA sequences, there may be phenotypic differences between them caused by somatic mutations and epigenetic changes affecting each genome. In this study, we collected eight families of MZ twins discordant for schizophrenia with the aim of investigating the potential role of mitochondrial DNA (mtDNA) heteroplasmy in causing the phenotypic differences between the twin pairs. Next-generation sequencing (NGS) technology was used to screen the whole mitochondrial genome of the twin pairs and their parents. The mtDNA heteroplasmy level was found to be nearly identical between the twin pairs but was distinctly different between each mother and their offspring. These results suggest that the discordance of schizophrenia between MZ twins may not be attributable to the difference in mtDNA heteroplasmy, and the high concordance of mtDNA heteroplasmy between MZ twins may indicate the relatively equal distribution of mtDNA during embryo separation of MZ twins and/or the modulation effect from the same nuclear genetic background. Furthermore, we observed an overrepresentation of heteroplasmy in noncoding regions and an elevated ratio of nonsynonymous heteroplasmy, suggesting the possible effects of a purifying selection in shaping the pattern of mtDNA heteroplasmy.
KeywordsMonozygotic twins mtDNA Heteroplasmy Schizophrenia
We are grateful to the subjects who donated DNA samples. We thank Ian Logan for helpful comments and language editing. This study was supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003), the National Natural Science Foundation of China (31171225, 81271484, 81471361, and 81371480), and the National Key Basic Research and Development Program (973) (Grant No. 2012CB517904).
Compliance with Ethical Standards
Conflict of Interest
- 18.Greaves LC, Nooteboom M, Elson JL, Tuppen HA, Taylor GA, Commane DM, Arasaradnam RP, Khrapko K et al (2014) Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing. PLoS Genet 10(9):e1004620CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Kloss-Brandstatter A, Weissensteiner H, Erhart G, Schafer G, Forer L, Schonherr S, Pacher D, Seifarth C et al (2015) Validation of next-generation sequencing of entire mitochondrial genomes and the diversity of mitochondrial DNA mutations in oral squamous cell carcinoma. PLoS One 10(8):e0135643CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Bi R, Zhang W, Yu D, Li X, Wang HZ, Hu QX, Zhang C, Lu W et al (2015) Mitochondrial DNA haplogroup B5 confers genetic susceptibility to Alzheimer’s disease in Han Chinese. Neurobiol Aging 36(3):1604.e7–16Google Scholar