title: Complete mitochondrial DNA genome sequence variation of Chinese families with mutation m.3635G>A and Leber hereditary optic neuropathy.
abstract: OBJECTIVE
  The majority of Leber hereditary optic neuropathy (LHON) cases are caused by one of three mitochondrial DNA (mtDNA) primary mutations (m.3460G>A, m.11778G>A, and m.14484T>C). In recent studies, we and others have shown that mutation m.3635G>A is a primary LHON mutation, particularly in Chinese. The purpose of this study was to perform a thorough analysis for the complete mtDNA genome sequence variation in Chinese patients with m.3635G>A and to identify potentially functional variants cosegregated with m.3635G>A.
  
  
  METHODS
  The complete mtDNA genomes of five Chinese patients with LHON carrying m.3635G>A were determined. A phylogenetic tree was constructed to distinguish the private and ancestral mtDNA variants in each lineage. Previously unreported variants in each mtDNA were defined with a web-based and database search. mtDNA variants that changed the structure of the membrane-spanning region of the protein were also evaluated, together with evolutionary conservation analysis, to predict their potential pathogenicity.
  
  
  RESULTS
  The five patients with LHON sequenced in this study belonged to haplogroups M7b4 (Le131), F1a (Le329 and Le337), B5b (Le569), and M7b6 (Le834), which suggested multiple origins of m.3635G>A. Private variants m.12811T>C, m.14063T>C, m.15237T>C, and m.9071C>T in these patients were predicted to change the structure of the membrane-spanning region of the respective proteins.
  
  
  CONCLUSIONS
  Mutation m.3635G>A had multiple origins in Chinese patients with LHON. We also identified several potentially functional variants cosegregated with m.3635G>A.
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, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Bi
authors.forename: A-Mei
authors.initials: AM
authors.lastname: Zhang
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Jia
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D054629:Genome, Mitochondrial; D006239:Haplotypes; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D010802:Phylogeny; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial