Scientists in Australia believe they have discovered the ancient origins of a rare form of childhood epilepsy caused by a genetic mutation: a single common ancestor who lived in Britain about 800 years ago. The find is particularly noteworthy because: hereditary disorders of this kind usually do not survive for such long in the population.
Epilepsy is a broad term for recurrent bursts of abnormal brain activity that cause neurological symptoms, especially seizures. It can have many different causes, including variations in our genes that are passed down between families. When these seizures are accompanied by a fever, they are also called febrile seizures.
This new study, led by researchers from the University of Melbourne’s Epilepsy Research Center, looked at childhood febrile seizure cases strongly linked to the SCN1Bc.363C>G variant. This variant has been found in multiple unrelated families in Australia, UK and US of the families had a long history of early epilepsy and the condition appears to be a dominant genetic disorder, meaning: a disease that can be caused by having only one copy of the bad gene. But the researchers were curious whether this mutation had been passed on from a solitary common ancestor to these affected families or whether it had arisen independently multiple times in human history.
The group attempted to trace the lineage of the SCN1Bc.363C>G variant in 14 families with these attacks. They also analyzed genome data from the UK Biobank, a large-scale and long-term study of human health that also their genetic information.
Within the biobank, the researchers identified another 74 individuals with the same variant. And all of these people had similar patterns of other genetic variations around the variant — a group of genes known as a haplotype. It’s highly unlikely that all of these people would have the same common haplotype without a shared ancestor, the researchers say, meaning the existence of this genetic disease today is likely due to just one ancestor, known as a single ancestor. founder event. And as far as they can tell, this ancestor lived about 800 years ago.
“Here we report evidence of a single founder event that gave rise to the SCN1Bc.363C>GQ11 variant in 14 independent families with epilepsy,” the authors wrote in their paper, published Tuesday in The American Journal of Human Genetics.
There are other genetic disorders or traits that can be clearly traced back to a single founder event. But these disorders usually occur later in life (after a person has already reproduced) or are recessive, meaning they only cause disease when someone inherits both copies of the bad variant. So it’s very unusual to see the same thing in a deleterious dominant mutation that shows up in childhood. Often, these mutations are eradicated in a short time, because affected people are less likely to survive into adulthood and pass the mutation on to the next generation – an example of natural selection.
This mutation, the authors speculate, might have endured because most people experience relatively mild seizures with it. Oonly about 70% of people with the mutation seem to get sick, something known as incomplete penetration. In other words, this mutation can cause problems, but not enough to stop people who had it from living their lives and passing on their genes.
Aside from learning more about this disease, the authors say their findings may have broader implications. There may very well be other genetic mutations that similarly linger in the population at low levels, but may actually turn out to be more harmful than currently believed.
“These findings suggest that variants present in the low-frequency population should be considered potentially pathogenic in mild phenotypes with incomplete penetrance and may be more important than previously thought,” they wrote.