杉本 研
   Department     ,
   Position  
Article types 原著
Language English
Peer review Peer reviewed
Title Direct linkage of mitochondrial genome variation to risk factors for type 2 diabetes in conplastic strains.
Journal Formal name:Genome research
Abbreviation:Genome Res
ISSN code:10889051/10889051
Domestic / ForeginForegin
Volume, Issue, Page 17(9),1319-1326頁
Author and coauthor Pravenec Michal, Hyakukoku Masaya, Houstek Josef, Zidek Vaclav, Landa Vladimir, Mlejnek Petr, Miksik Ivan, Dudová-Mothejzikova Kristyna, Pecina Petr, Vrbacky Marek, Drahota Zdenek, Vojtiskova Alena, Mracek Tomas, Kazdova Ludmila, Oliyarnyk Olena, Wang Jiaming, Ho Christopher, Qi Nathan, Sugimoto Ken, Kurtz Theodore
Publication date 2007/09
Summary Recently, the relationship of mitochondrial DNA (mtDNA) variants to metabolic risk factors for diabetes and other common diseases has begun to attract increasing attention. However, progress in this area has been limited because (1) the phenotypic effects of variation in the mitochondrial genome are difficult to isolate owing to confounding variation in the nuclear genome, imprinting phenomena, and environmental factors; and (2) few animal models have been available for directly investigating the effects of mtDNA variants on complex metabolic phenotypes in vivo. Substitution of different mitochondrial genomes on the same nuclear genetic background in conplastic strains provides a way to unambiguously isolate effects of the mitochondrial genome on complex traits. Here we show that conplastic strains of rats with identical nuclear genomes but divergent mitochondrial genomes that encode amino acid differences in proteins of oxidative phosphorylation exhibit differences in major metabolic risk factors for type 2 diabetes. These results (1) provide the first direct evidence linking naturally occurring variation in the mitochondrial genome, independent of variation in the nuclear genome and other confounding factors, to inherited variation in known risk factors for type 2 diabetes; and (2) establish that spontaneous variation in the mitochondrial genome per se can promote systemic metabolic disturbances relevant to the pathogenesis of common diseases.
DOI 10.1101/gr.6548207
PMID 17693571