A recent study has found several genes associated with autism and discovered evidence for a shared genetic mechanism in both autism and fragile X syndrome. Fragile X syndrome is a genetic condition involving changes in part of the X chromosome and is the most common genetic cause of intellectual disability.
Genetic variation caused by mutation leading to autism spectrum disorders is well established, and research has repeatedly implicated “de novo” (new) mutations, those that show up for the first time in affected children, as being especially pertinent. Identification of the specific genes connected to autism may lead to vital advances in the diagnosis and treatment of autism spectrum disorders. The current study, led by Dr. Michael Wigler from Cold Spring Harbor Laboratory, used gene sequencing methods to look at nearly 350 families with healthy children and children on the autistic spectrum, part of the larger Simons Simplex Collection. Specifically, the researchers looked for mutations that were present in the children but not in their parents.
The researchers found that autism is linked with the types of new mutations that are likely to disrupt the function of a gene. By disrupting one of the pair of healthy genes that we normally inherit, such mutations alter “gene dosage.” There was double the incidence of such mutations in the affected child than in the healthy child, but little to no difference in the overall incidence of much more common types of mutations. The results also showed that children with older parents have more new mutations. This is in line with other recent reports and possibly explains why older parents are more likely to have children on the autism spectrum. “More generally, this work and the work preceding it point to the importance of new mutations and gene dosage in so-called complex genetic disorders,” says Dr. Wigler.
The study also identified many new autism candidate genes, and these genes showed a strong overlap with genes linked to the pathway involved in fragile X syndrome, one of the best studied cognitive-behavioral disorders in humans. “We observe strong statistical evidence for the link between autism and fragile X syndrome, first suggested by study coauthors Dr. Jennifer Darnell and Dr. Robert Darnell, in a paper they published in Cell last year,” explains Dr. Wigler. “Our finding has important implications for therapy and shows that autism is in large part a molecular disorder of neuroplasticity, the mechanisms by which our nervous system adapts to change.”
Ivan Iossifov, Michael Ronemus, Dan Levy, Zihua Wang, Inessa Hakker, Julie Rosenbaum, Boris Yamrom, Yoon-ha Lee, Giuseppe Narzisi, Anthony Leotta, Jude Kendall, Ewa Grabowska, Beicong Ma, Steven Marks, Linda Rodgers, Asya Stepansky, Jennifer Troge, Peter Andrews, Mitchell Bekritsky, Kith Pradhan, Elena Ghiban, Melissa Kramer, Jennifer Parla, Ryan Demeter, Lucinda L. Fulton, Robert S. Fulton, Vincent J. Magrini, Kenny Ye, Jennifer C. Darnell, Robert B. Darnell, Elaine R. Mardis, Richard K. Wilson, Michael C. Schatz, W. Richard McCombie, Michael Wigler. De Novo Gene Disruptions in Children on the Autistic Spectrum. Neuron, 2012; 74 (2): 285 DOI:10.1016/j.neuron.2012.04.009
Cold Spring Harbor Laboratory (2012, April 25). A striking link is found between the Fragile-X gene and mutations that cause autism. ScienceDaily. Retrieved April 27, 2012, from http://www.sciencedaily.com/releases/2012/04/120425140359.html