The study, which highlights the role of mitochondrial genome variation in the pathogenesis of common diseases, is published online in Genome Research (www.genome.org).
According to the Centers for Disease Control, 7% of the U.S. population has diabetes, and 90-95% of those cases are classified as type 2 diabetes. Type 2 diabetes is caused by external factors such as diet and exercise, and is influenced by several genes. While most of the genes known to be involved in diabetes susceptibility are located in the nuclear genome, a recent study estimated that more than 20% of type 2 diabetes cases may involve mutations in the mitochondrial genome.
In the study published today, the scientists compared two different rat strains; the strains possessed virtually identical nuclear genomes but different mitochondrial genomes. This eliminated any complicating effects due to environmental factors or variation in the nuclear genome. Any differences observed between the two rat strains could be attributed to variation in the mitochondria.
When comparing the two rat strains, the researchers found that the two strains exhibited significant differences related to energy metabolism and storage. One rat strain exhibited impaired glucose tolerance, reduced muscle glycogen synthesis, decreased skeletal muscle ATP (energy) levels, and decreased activity of an energy-producing enzyme called cytochrome c oxidase, when compared to the second rat strain. These metabolic characteristics are typical of diabetic individuals.
The researchers then obtained DNA sequences from mitochondria of both rat strains, and found DNA variants in genes that encode for proteins involved in energy production. Thus, for the first time, they were able to directly link inherited variation in the mitochondrial genome to metabolic markers for type 2 diabetes.
“Our study highlights the role of mitochondrial DNA variation in common genetic diseases,” says Dr. Theodore Kurtz, the lead investigator on the project. “In addition, the animal models developed in this study will open the door for future studies in which the effects of mitochondrial genome variation can be investigated on fixed nuclear genetic backgrounds.”
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The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
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