By Carl Zimmer
The family seemed to defy the rules of genetics.
When Meriel M. McEntagart, a geneticist at St. George’s University of London, met the family in May 2012, she suspected that three of the children had a rare genetic disorder called Smith-Magenis syndrome. They had many of the symptoms of the disease, such as trouble sleeping through the night. Dr. McEntagart confirmed that diagnosis with a genetic test. The children were all missing an identical chunk of a gene known as RAI1.
One of the children had a different father from the other two, and so the mother could be the only source of their altered gene. But when Dr. McEntagart ran a standard blood test on the mother, the results were not nearly so straightforward: The woman had a normal version of RAI1.
Dr. McEntagart and her colleagues suspected that the answer to this puzzle was that the mother was a genetic mosaic.
We tend to think of ourselves as having just one set of genetic material, which exists in identical form in every one of our cells. But sometimes, people have two or more significantly different genomes. As our cells divide, some may go through a major mutation. So some individuals end up with groups of cells that have very different DNA from the rest of them.
Dr. McEntagart said that she suspected that the mother she encountered had a normal version of RAI1 in some cells but an altered version in other cells, including her eggs.
“We wanted to understand if there was a way to demonstrate that she was a mosaic,” Dr. McEntagart said.
Dr. McEntagart got wind that researchers at Baylor College of Medicine in Houston were developing new methods for pinpointing mosaics, and they confirmed that the mother was indeed a mosaic. Some of her cells carried the Smith-Magenis syndrome mutation.
Scientists have known about mosaicism for decades, but they’ve studied it mostly on a case-by-case basis. As a result, it has been hard to tell if the kind of mosaicism Dr. McEntagart encountered was a fluke, or if it was common enough to be medically important.
In a study released Thursday in the American Journal of Human Genetics, the Baylor team and its colleagues describe the biggest search for cases in which mosaic parents passed down disease-causing mutations to their children. It turns out to be far from a fluke.
“This happens a surprising amount of the time,” said Chad A. Shaw, a co-author of the new study.
Michael Snyder, a geneticist at Stanford University who was not involved in the study, said it showed that mosaicism could have a significant effect on not just people’s own health, but on their children as well.
“We will have to be on the lookout for these types of events,” he said.