Genetics of autism
- Studies show potent influence of various genetic defects in mosaic responsible for autism
A Coruña, March 5th, 2021. Autism is a neurodevelopmental disorder characterized by deficits in communication and social interaction, with altered behavior. Autism has an important genetic basis, with multiple inherited genomic defects and also with de novo mutations. De novo mutations contribute to 30% of the cases of children whose autism appears for the first time in the family. The main source of new mutations in these children is due to repeats of 1 to 20 base pairs distributed in different places of the genome, as demonstrated by an excellent work of Ileena Mitra, from the Bioinformatics and Systems Biology Program, and the group of Melissa Gymrek, from the Department of Medicine of the University of California, La Jolla, San Diego.
Another study by Maxwell A. Sherman, from the Division of Genetics of the Department of Medicine at Harvard University and the Massachusetts Institute of Technology (MIT) in Boston, demonstrates the genesis of CNVs(copy number variants) in the germ cells of children with autism, which are formed very early in development. In this study, with 12,077 probands with autism and 5500 healthy relatives, the authors detected 46 new mutations in CNVs of probands and 19 mCNVs in relatives, affecting cells in a range of 2.8% and 73.8%. The higher the number of CNVs, the higher the risk of autism.
In a third paper, Rachel E. Rodin and her team, from the Division of Genetics and Genomics at the Howard Hughes Medical Institute, Boston Children's Hospital, and the Departments of Pediatrics and Neurology at Harvard University, demonstrated the presence of somatic mutations in the prefrontal cortex, with a ratio of more than 3 mutations per cell in early post-fertilization divisions (with an average of 24 somatic mutations per brain in more than 4% of brain cells).
This work demonstrates the powerful influence of various genetic defects in mosaic responsible for autism and the possibility of using new genomic biomarkers for an effective diagnosis of this disease early in life and to be able to intervene in support of the neurodevelopment of affected children.
References
- Mitra, I. et al. Patterns of de novo tandem repeat mutations and their role in autism. Nature 2021; 589:246-250.
- Sherman, M. A. et al. Large mosaic copy number variations confer autism risk. Nat. Neurosci. 2021; 24:197-203.
- Rodin, R. E. et al. The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing. Nat. Neurosci. 2021; 24:176-185.
