Science News
from research organizations

How Mitochondrial Disease Is Passed Down From Mother To Child: Predicting Severity

January 31, 2008
Virginia Tech
Scientists have shown for the first time how a particular family of diseases are passed down from mother to child and how this can lead to the severity of the disease differing widely. The research offers new hope of being able to predict a child's risk of developing a mitochondrial disease which can cause muscle weakness, diabetes, strokes, heart failure and epilepsy.

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 patient's cells will contain a mixture of mutant and normal mtDNA. The proportion of mutant mtDNA in most cases determines the severity of the disease. Defective mitochondria cause most damage in muscles, nerves and the brain, the parts of the body which consume the most energy.

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 were both essential for this study. The experiments gave us new information that we had to have to build the simulation, and the simulation was used as a tool to analyze the data from the experiment."

Dr. Patrick Chinnery, Wellcome Senior Fellow in Clinical Science and professor of neurogenetics at the University of Newcastle in the United Kingdom, remarked: "Mitochondrial disease can have devastating effects on a family, and the chance of having affected children is a cause of major stress. By defining the main biological mechanism, we hope in the long term to develop counseling guidelines that will help patients and their families make more informed decisions."

The computational model reveals how mtDNA is divided into different embryonic cells before and after implantation and how the replicating mtDNA molecules are subsequently separated between the dividing germ cells that make up the embryo. The model accounts for the marked reduction in the number of mtDNA molecules that are transmitted from mother to offspring, the so-called "mitochondrial genetic bottleneck." It is thought that this genetic bottleneck has evolved over time to remove deleterious mitochondrial mutations from the population. These mutations are either lost during transmission or, if transferred, give rise to offspring with a low chance of survival.

A woman's eggs are formed at a very early stage in her development. As a precursor cell divides into a number of eggs, so the mitochondria from that cell are distributed randomly throughout these eggs. Hence different eggs can contain very different amounts of mutant mtDNA, which determine the amount of mutant genetic material that is passed on to the next generation. This difference is thought to explain the variation in the severity of the disease between siblings however the mechanism responsible for this variation was not understood for many years.

"In essence, it's a game of chance," explains Professor Chinnery. "If you have a mixture of red and white balls and pick handfuls at random, then some of those handfuls will contain very few red balls and other very few white ones. We have shown this is the reason for the different amounts of mutant mtDNA in different eggs."

Although the current study investigates the transmission of mitochondrial DNA in mice, the computational model is also applicable to human data. Mitochondrial diseases are thought to affect as many as one person in 5000. The research offers the hope that clinicians will be able to predict a child's risk of developing maternally inherited mitochondrial diseases that cause muscle weakness, diabetes, stroke, heart failure and epilepsy.

* Journal reference: Lynsey M Cree, David C Samuels, Susana Chuva de Sousa Lopes, Harsha Karur Rajasimha, Passorn Wonnapinij, Jeffrey R Mann, Hans-Henrik M Dahl, Patrick F Chinnery (2008) "A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes," Nature Genetics,

This research is supported by the Wellcome Trust and the Thailand Higher Education Strategic Scholarship for Frontier Research Network.

Story Source:

Materials provided by Virginia Tech. Note: Content may be edited for style and length.

Cite This Page:

Virginia Tech. "How Mitochondrial Disease Is Passed Down From Mother To Child: Predicting Severity." ScienceDaily. ScienceDaily, 31 January 2008. <>.
Virginia Tech. (2008, January 31). How Mitochondrial Disease Is Passed Down From Mother To Child: Predicting Severity. ScienceDaily. Retrieved March 30, 2017 from
Virginia Tech. "How Mitochondrial Disease Is Passed Down From Mother To Child: Predicting Severity." ScienceDaily. (accessed March 30, 2017).