RT Journal
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
JF Genome Research 
JO Genome Research 
YR 2007 
FD September 01 
VO 17 
IS 9 
SP 1319 
OP 1326 
DO 10.1101/gr.6548207 
UL http://genome.cshlp.org/content/17/9/1319.abstract 
AB 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.