New hope for disease prediction

For the first time, scientists can now show how a particular family of diseases is passed down from mother to child, and how this can lead to the severity of the disease differing widely.

This research, funded by the Wellcome Trust, has proved that there is a ‘mitochondrial genetic bottleneck’, where only a small number of Mitochondria DNA (mtDNA) molecules in the mother are passed on to the next generation.

An international team of collaborators have shown in mice that this bottleneck does exist and causes the dramatic reduction in the number of mtDNA molecules in the cells that eventually form the eggs.

“Inheritance of mitochondrial diseases within families has proved incredibly difficult to predict,” says Prof Patrick Chinnery of Newcastle University and a Wellcome Trust Senior Clinical Research Fellow.

“A mother can pass on a small proportion of mutant mtDNA, or a very high proportion, and this can make the difference between a child being born without disease and another having a very severe form of the disease.”

The research offers hope of being able to predict a child’s risk of developing a mitochondrial disease, a disease that carries genetic features, which can cause muscle weakness, diabetes, strokes, heart failure and epilepsy.

All cells contain many mitochondria, which are involved in energy production within the body. Mitochondria have their own genetic information, known mtDNA, which is inherited solely from the mother.

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.

“In essence, it’s a game of chance,” explains 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 others very few white ones. We have shown this is the reason for the different amounts of mutant mtDNA in different eggs.

“With conventional genetics, we’re able to say, for example, that if you carry a certain gene, your child has a one in 10 chance of developing a particular disease. Now that we understand how different levels of abnormal mtDNA are inherited, we may soon be able to predict a child’s risk of disease and the level of severity.”