Control of monoallelic expression of the Angelman gene UBE3A
The gene disrupted in AS, UBE3A, is unique because its action is controlled by a remote DNA region that is called the imprinting center(IC). In the normal brain, this IC turns off the UBE3A that the father contributed (on chromosome 15) but turns on UBE3A on the number 15 chromosome contributed by the mother. Individuals with AS are thus missing the function of the maternally derived UBE3A. ASF funded this investigator to learn more about how the IC turns UBE3A on and off. This was an effort by ASF to promote molecular research on the IC and complement ASF’s promotion of human clinical trials to provide dietary supplements in hope of modulating the action of the imprinting center. Many publications arose from this work and more evidence supports the fact that the paternal IC is not methylated while the maternal IC is methylated.