Researchers led by University of Montreal scientists discovered how new or de novo gene mutations — alterations of the cell’s DNA — play a role in these devastating conditions.
New (de novo) mutations are alterations of the cell’s DNA that can occur because of errors in the DNA replication, which happen prior to cell division. Once DNA is changed, this mutation is passed down to a next generation. These de novo mutations are newly formed within each individual, and are not inherited from either parent.
The study, which has implications for disease prevalence and severity, is published in the American Journal of Human Genetics.
“This study emphasizes the importance of de novo mutations as genetic factors predisposing to autism and schizophrenia. We found an increased frequency of severe de novo mutations in critical brain genes in both of these diseases,” says senior author and University of Montreal professor Guy Rouleau.
“Harmful de novo mutations, as observed in this study, may in part explain the high global incidences of autism and schizophrenia,” adds Dr. Rouleau.
As part of the investigation of human mutation rates, the team analyzed 400 genes that are turned on in nerve cells from patients with autism or schizophrenia spectrum disorders. Their results showed that there is an excess of de novo gene mutations associated with the two diseases.
The study also revealed that DNA taken directly from the patient’s blood was superior to that taken from patient-derived cell lines.
“The source of biological material is crucial for these types of experiments,” says lead author Philip Awadalla, a University of Montreal pediatrics professor.
“In the process of confirming our findings, we were also able to provide one of the first direct estimates of the human mutation rate,” continues Dr. Awadalla.
“The number of mutations per generation is extremely small but on the order of what was previously indirectly inferred for human-chimpanzee comparisons. We also discovered that mutations can be introduced when cell lines are produced, which creates false-positive results. This artifact can significantly bias results and therefore great care needs to taken when analyzing these samples.”
Source: University of Montreal