Somatic mutations naturally occur in cells throughout human development and during aging. However, it has yet to be determined whether the frequency of somatic mutations in the population are a contributing factor to the cause of neuropsychiatric disorders, cancers, and various diseases.
Alexej Abyzov, Ph.D., a Mayo Clinic genomics researcher, seeks to gain a better understanding of genomic variants so that one day it will be possible to identify individual genetic risks in diseases, monitor these risks during a person’s lifetime, personalize medical treatment and improve therapy.
In a study released in Science, Mayo Clinic researchers analyzed the somatic variants in 131 human brains. The analysis included 44 neurotypical brains, 19 with Tourette syndrome, nine with schizophrenia, and 59 with an autism spectrum disorder.
Researchers highlighted the following findings:
“We found that a subset of brains has elevated mutation burden, i.e., hypermutable," says Dr. Abyzov, lead author. “Given the association of hypermutability with age and its frequent localization in one brain region, we hypothesized that it could be related to gliogenesis in adult brains.”
Gliogenesis refers to the formation of glial cells from their multipotent stem cells. Dr. Abyzov explains gliogenesis is important especially in the developmental stage to construct brain structure and impairments to gliogenesis at any stage of life are associated with many neurological disorders.
“It could be relevant to cognitive aging, such as Parkinson’s and Alzheimer’s disease, or hypermutability could be a remnant of a brain tumor that escaped earlier in life,” he says. “It has yet to be determined whether the frequency of mutations in the population contribute to the cause of neuropsychiatric disorders.”
The authors reported that the autism spectrum disorder cohort was the only one where deletions were detected in the individual genomes. Brains with autism were associated with mutations in enhancer-like regions in the developing brain, suggesting a potential link between their involvement in gene regulation and autism.
Dr. Abyzov notes future research establishing the cause and extent of hypermutability will require analysis of larger sets of brains and additional analyses at the single-cell level.
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