title: Mitochondrial genome variations and functional characterization in Han Chinese families with schizophrenia.
abstract: The relationship between mitochondrial DNA (mtDNA) variants and schizophrenia has been strongly debated. To test whether mtDNA variants are involved in schizophrenia in Han Chinese patients, we sequenced the entire mitochondrial genomes of probands from 11 families with a family history and maternal inheritance pattern of schizophrenia. Besides the haplogroup-specific variants, we found 11 nonsynonymous private variants, one rRNA variant, and one tRNA variant in 5 of 11 probands. Among the nonsynonymous private variants, mutations m.15395 A>G and m.8536 A>G were predicted to be deleterious after web-based searches and in silico program affiliated analysis. Functional characterization further supported the potential pathogenicity of the two variants m.15395 A>G and m.8536 A>G to cause mitochondrial dysfunction at the cellular level. Our results showed that mtDNA variants were actively involved in schizophrenia in some families with maternal inheritance of this disease.
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: Institute of Mental Health, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Tang
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: Wen
authors.initials: W
authors.lastname: Zhang
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: Xiao
authors.initials: X
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: Shi-Yi
authors.initials: SY
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.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yu
authors.affiliation: Institute of Mental Health, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
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; CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: yaoyg@mail.kiz.ac.cn.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000502:physiology; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D017382:Reactive Oxygen Species / Q000378:metabolism; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D014162:Transfection
chemical_list: D004272:DNA, Mitochondrial; C501005:MT-ATP6 protein, human; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases
keywords: Allotopic expression; Maternal inheritance; Private variant; Schizophrenia; mtDNA