In a novel research, funded by the Wellcome Trust, scientists have cracked a "mitochondrial genetic bottleneck", by which a particular family of diseases is passed down from mother to child and leads to the severity of the disease differing widely.
The findings may enable them the scientists to predict a child's risk of developing a mitochondrial disease causing muscle weakness, diabetes, strokes, heart failure and epilepsy.
The research has proven that there is a "mitochondrial genetic bottleneck", where only a small number of mtDNA molecules in the mother are passed on to the next generation.
All human and animal cells contain many mitochondria, responsible for energy production in the body. These mitochondria have their own genetic information, known as mitochondrial DNA, or mtDNA, which is inherited. Although, a child inherits one copy of DNA from each parent, a child may inherit many copies of mtDNA, which are only passed down from the mother.Mutations in mtDNA can affect energy production within cells and thus causes the disease.
Though, mitochondrial diseases differ both in location and severity depending on where and at what levels the mutations are distributed, defective mitochondria leads to maximum damage in muscles, nerves and the brain, as these are the parts of the body consuming most of the energy.
"Inheritance of mitochondrial diseases within families has proved incredibly difficult to predict. 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," said Professor Patrick Chinnery, a Wellcome Trust Senior Clinical Research Fellow at Newcastle University.
He explained: "In essence, it's a game of chance. 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."
The eggs of a woman are formed at a very early stage in her development. When a precursor cell divides into a number of eggs, the mitochondria from that cell are distributed randomly throughout these eggs. Thus different eggs can contain different amounts of mutant mtDNA, determining the amount of mutant genetic material passed on to the next generation.
This difference is believed 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 the new research, it has been shown in mice that this bottleneck does exist and causes the remarkable reduction in the number of mtDNA molecules in the cells that ultimately form the eggs. This may cause a wide variation in the severity of disease.
A high proportion of abnormal mitochondria may be passed on to the child, depending on which egg is fertilised. Here, the child will be more severely affected than the mother.
Though mitochondrial diseases were once considered rare, they are now believed to affect almost one person in 5,000. Although, even when the precise proportion of abnormal mtDNA carried by the mother is known, it has not been predicted whether and how a child will be affected.
Professor Chinnery hopes that this new research will open up opportunities for predicting disease risk.
"With conventional genetics, we're able to say, for example, that if you carry a certain gene, your child has a one in ten 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. ," he said.
The study is published online in the journal Nature Genetics.