Molecular Neurobiology

, Volume 54, Issue 6, pp 4343–4352 | Cite as

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.


Monozygotic 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


Supplementary material

12035_2016_9996_MOESM1_ESM.doc (158 kb)
ESM 1 (DOC 157 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Institute of Mental Health of the Second Xiangya Hospital of Central South University, The China National Clinical Research Center for Mental Health Disorders, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan ProvinceChangshaChina
  2. 2.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan ProvinceKunming Institute of ZoologyKunmingChina
  3. 3.Kunming College of Life Science, University of Chinese Academy of SciencesKunmingChina
  4. 4.Department of Psychiatrythe First Affiliated Hospital of China Medical UniversityShenyangChina
  5. 5.CAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghaiChina
  6. 6.Department of Psychiatrythe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

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