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Mitochondrial DNA Sequence Diversity in Bipolar Affective Disorder

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.METHOD: 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.

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				D. C. Wallace Mitochondria as Chi Genetics, June 1, 2008; 179(2): 727 - 735. [Full Text] [PDF]

				E. Ruiz-Pesini, M. T. Lott, V. Procaccio, J. C. Poole, M. C. Brandon, D. Mishmar, C. Yi, J. Kreuziger, P. Baldi, and D. C. Wallace An enhanced MITOMAP with a global mtDNA mutational phylogeny Nucleic Acids Res., January 12, 2007; 35(suppl_1): D823 - D828. [Abstract] [Full Text] [PDF]

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