Nature Genetics paper says process occurs during egg maturation.



Researchers at the Montreal Neurological Institute, McGill University have located a genetic bottleneck that ascertains the proportion of mutated mtDNA that mothers transmit to their offspring.


The study locates the bottleneck as occurring during egg development in the early postnatal life of a female, supporting the knowledge that mature oocytes or egg cells contain the full set of copies of mtDNA. This evidence enables preimplantation genetic diagnosis such as for in-vitro fertilization, which involves an oocyte being screened for harmful mutations prior to fertilization.


“The proportion of mutated DNA copies shifts rapidly and unpredictably from mother to child making it very hard to predict what proportion of mutated DNA will be passed on,” notes Eric Shoubridge, Ph.D., neuroscientist at the MNI and lead investigator in the study. “We now understand that this is partly due to the genetic bottleneck, in which just a small number of the original mtDNA copies from the mother are actually transmitted to the child.


“This bottleneck occurs during the development of eggs in affected females. Only a small set of the female’s mtDNA is selected to replicate resulting in the individual producing eggs with a wide range of proportions of mutated mtDNA. These eggs give rise to offspring with proportions of mutated mtDNA that differ from each other and are different from the proportion of mutated mtDNA in the mother.


“This explains why the occurrence and severity of a disease from mutated mtDNA can vary in offspring of an affected mother,” Dr. Shoubridge concludes.


The study is published in the December issue of Nature Genetics.