“Genetic studies are showing that there will be about 1,000 genes linked to autism. This means you could mutate any one of them and get the disorder. We found how one of these mutations works,” said Zylka, senior author of the Cell paper and member of the UNC Neuroscience Center.
The work was done in human cell lines, as well as mouse models.
Because this one autism-linked UBE3A mutation was part of the Simons Simplex Collection – and Zylka previously had been funded through a Simons Foundation grant – he had access to the cells that were used to find this one mutation. When Jason Yi, PhD, a postdoctoral fellow in Zylka’s lab, sequenced the genes from the cell samples – including cells from the child’s parents – he found that the parents had no hyperactive UBE3A but the child did.
The child’s regulatory switch was broken, causing UBE3A to be perpetually switched on.