- Awarded: 2014
- Award Type: Research
- Award #: 306063
Comprehensive studies of the human genome using high-speed DNA sequencing have identified new genes whose mutations appear to contribute to autism. One class of autism genes consists of regulators of the way that cells, including neurons in the brain, compact their DNA so that it can fit into the nucleus of the cell, while also being available for the selective production of proteins required for brain function. These genes, called chromatin regulators, appear to be among the most frequently mutated genes in individuals with autism. It seems that chromatin regulators control the production of proteins necessary for the development of neural circuits, and perhaps transmission of electrical impulses in the brain.
Gerald Crabtree and his colleagues at Stanford University in California are using genetic and biochemical approaches to understand how chromatin regulators may contribute to autism. They intend to determine how chromatin regulators function in normal brain development. In mice, chromatin regulators are essential for normal brain development, but their mechanisms of action are relatively unclear.
Crabtree’s group previously discovered a neuron-specific chromatin regulator called nBAF, which is related to the yeast SWI/SNF chromatin regulator. The subunits that make up the nBAF complex are repeatedly mutated in autism, and other research groups have found that one of the mutated subunits is capable of directing the formation of specific neural circuits. One characteristic of the autism-linked mutations affecting nBAF function is that they alter only one of two alleles of the genes encoding its subunits. If these molecules can boost the activity of the remaining normal allele, it might offer a path to treatment for individuals with autism.