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In silico modeling helps predict severity of mitochondrial disease
Date:1/27/2008

A team of researchers in Australia, the United Kingdom and the United States has revealed how mitochondrial diseases are passed from the mother to the next generation in a mouse model system. The study, which was published on-line in Nature Genetics*, shows for the first time how mitochondrial diseases that cause muscle weakness, diabetes, stroke, heart failure and epilepsy are passed from mother to offspring.

Mitochondria are the engines present in each cell that produce adenosine triphosphate (ATP), the key energy currency that drives metabolism. Mitochondria also have their own DNA (mitochondrial or mtDNA) that encodes a small but essential number of proteins required for energy production in cells. Mitochondria, and the mtDNA that they contain, are inherited solely from the mother, as the paternal mtDNA present in the sperm are destroyed after the egg is fertilized. In almost all diseases caused by mutant mtDNA, the patients cells will contain a mixture of mutant and normal mtDNA. The proportion of mutant mtDNA in most cases determines the severity of the disease.

The inheritance of these diseases does not follow the rules of Mendelian genetics. Instead, there are large random shifts at the mtDNA mutation level between mother and offspring. This study explains how these large random shifts occur within the first three weeks of embryo formation, through the combined use of computational modeling and a mouse model system.

Dr. David Samuels, assistant professor at the Virginia Bioinformatics Institute (VBI), commented: The computational model used in this investigation simulates the biological process directly and allows scientists to examine the early stages of embryo formation and development. Clinicians can therefore take a close look at the replication of mitochondrial DNA and the dynamics of cell division in mouse embryos before and after implantation in the uterus. He added: Computational modeling and cutting-edge lab work we
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Contact: Barry Whyte
whyte@vbi.vt.edu
540-231-1767
Virginia Tech
Source:Eurekalert

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