title: mtDNA Heteroplasmy in Monozygotic Twins Discordant for Schizophrenia.
abstract: 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.
authors.affiliation: 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 Province, Changsha, Hunan, 410011, China.|Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Bi
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, the First Affiliated Hospital of China Medical University, Shenyang, 110122, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Tang
authors.affiliation: 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 Province, Changsha, Hunan, 410011, China.
authors.forename: Zongchang
authors.initials: Z
authors.lastname: Li
authors.affiliation: 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 Province, Changsha, Hunan, 410011, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: 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 Province, Changsha, Hunan, 410011, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: 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 Province, Changsha, Hunan, 410011, China. tangjinsonghn@gmail.com.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Tang
authors.affiliation: 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 Province, Changsha, Hunan, 410011, China. chenxghn@163.com.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China. yaoyg@mail.kiz.ac.cn.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China. yaoyg@mail.kiz.ac.cn.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China. yaoyg@mail.kiz.ac.cn.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D054629:Genome, Mitochondrial; D018095:Germ-Line Mutation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial
keywords: Heteroplasmy; Monozygotic twins; Schizophrenia; mtDNA