About Angelman Syndrome
The place to begin is here, with a picture of a normally functioning Chromosome 15.
Focus on the orange region, known as q11-q13, which appears on both the maternal (mother’s) and paternal (father’s) copies. That’s the area in charge of producing the UBE3A protein from the UBE3A gene, a protein that helps us walk, talk and perform many other everyday tasks.
Here’s where things get tricky. In most tissues in the body (again, we’re still talking about typically functioning individuals without Angelman syndrome), UBE3A is expressed from both the paternal and maternal chromosomes 15. But in neurons in the brain, the paternal UBE3A allele is silenced by a process known as imprinting. This is the case in all of us. We all have a silent paternal copy of the UBE3A gene. As a result, in the neurons of individuals without AS, only the maternal UBE3A allele is expressed; the paternal side is silent.
In other words: “neurotypical” = maternal side functioning, paternal side silent.
But what happens if something goes wrong with the maternal gene—leaving you with a nonfunctioning maternal gene and a silent paternal one? Or with two silent paternal genes, in rare cases? Meaning, what happens when neither side is properly expressing the UBE3A gene, or there is limited production of the resultant UBE3A protein?
What happens is Angelman syndrome. This can look differently depending on how this happens.
More specifically, when this maternal gene is able to be properly read, than it produces messenger RNA (mRNA). You can think of mRNA as a message that was translated from the DNA, which is then able to be better understood by the cell. The mRNA leaves the nucleus of the cell as a blueprint of each gene, and brings the translated message to the protein-assembly factories of our cells. People with AS have a defect in their UBE3A gene, and that interrupts this translation service. As a result, their neurons do not make functional UBE3A protein, and that’s what triggers the symptoms of AS.
In most cases, Angelman syndrome isn’t inherited—particularly those caused by a deletion or UPD. Instead, these genetic changes occur as random events during the formation of reproductive cells or in early embryonic development.
For the best overview of AS genetics (and in under 10 minutes of watching time!)