title: Mitochondrial DNA sequence diversity in bipolar affective disorder.
abstract: OBJECTIVE
  Point mutations in mitochondrial DNA (mtDNA) are one mechanism that could explain the apparent excess maternal transmission of bipolar affective disorder observed in some families. The authors sequenced the mtDNA from probands with bipolar disorder and tested nucleotide variants for association with the disorder.
  
  
  METHODS
  The entire 16.5 kilobase mitochondrial genome was sequenced in nine unrelated probands selected from large pedigrees with exclusively maternal transmission of bipolar affective disorder. Compared to a reference sequence, variants were detected at 107 nucleotide positions. Fifteen variants of possible pathogenic significance were selected for further study. These variants were assayed in 93 unrelated probands with bipolar I, bipolar II, or schizoaffective-manic disorder and 63 comparison subjects, all of whom were classified into the major groups comprising the European mtDNA haplotype structure (haplogroups).
  
  
  RESULTS
  The major European haplogroups were represented at the expected frequencies among both probands and comparison subjects. There was no significant difference between probands and comparison subjects in the frequency of any variant, although odds ratios >2 or <0.5 were observed for four variants. Frequencies of these four variants were similar in probands and haplogroup-matched comparison subjects. The results of all comparisons were essentially unchanged when probands from families with an apparently paternal transmission pattern were excluded.
  
  
  CONCLUSIONS
  The results demonstrate that bipolar affective disorder occurs across all of the major European mtDNA haplogroups but do not reveal any point mutations that explain excess maternal transmission of the disorder.
authors.affiliation: Department of Psychiatry, University of Chicago, IL 60637, USA. fmcmahon@midway.uchicago.edu
authors.forename: F J
authors.initials: FJ
authors.lastname: McMahon
authors.forename: Y S
authors.initials: YS
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: J
authors.initials: J
authors.lastname: Kokoszka
authors.forename: M D
authors.initials: MD
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Torroni
authors.forename: J R
authors.initials: JR
authors.lastname: DePaulo
authors.forename: D C
authors.initials: DC
authors.lastname: Wallace
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers; D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014960:X Chromosome / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers