TY  - JOUR
A1  - Pravenec, Michal
A1  - Hyakukoku, Masaya
A1  - Houstek, Josef
A1  - Zidek, Vaclav
A1  - Landa, Vladimir
A1  - Mlejnek, Petr
A1  - Miksik, Ivan
A1  - Dudová-Mothejzikova, Kristyna
A1  - Pecina, Petr
A1  - Vrbacký, Marek
A1  - Drahota, Zdenek
A1  - Vojtiskova, Alena
A1  - Mracek, Tomas
A1  - Kazdova, Ludmila
A1  - Oliyarnyk, Olena
A1  - Wang, Jiaming
A1  - Ho, Christopher
A1  - Qi, Nathan
A1  - Sugimoto, Ken
A1  - Kurtz, Theodore
T1  - Direct linkage of mitochondrial genome variation to risk factors for type 2 diabetes in conplastic strains
Y1  - 2007/09/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1319 
EP  - 1326 
DO  - 10.1101/gr.6548207 
VL  - 17 
IS  - 9 
UR  - http://genome.cshlp.org/content/17/9/1319.abstract 
N2  - 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. 
ER  -