Families & Caregivers
Genetics 101
This section reviews basic genetics concepts. For a a deeper dive, check out Genetics 201.
Our bodies are made of tiny building blocks called cells, and inside almost every cell, most people have 46 chromosomes. Think of chromosomes as instruction books that tell our bodies how to grow and work. The chromosomes are arranged in pairs, and we typically get 23 chromosomes from our mother (maternal) and 23 from our father (paternal), for a total of 46 chromosomes.
The chromosomes are made up of DNA and contain our genes. Each gene gives an instruction to make a protein. Proteins do essentially everything in our body—controlling growth, development, and everyday functioning.
One important gene is called UBE3A, which is found on chromosome 15. This gene gives instructions to make the UBE3A protein. UBE3A protein is needed for activities like walking and talking. Because most people have two copies of chromosome 15, most people have two copies of the UBE3A gene.
In most body tissues, both copies of the UBE3A gene (one from each parent) are turned on. However, in brain cells, specifically neurons, only the maternal copy of UBE3A is turned on. Due to a process called imprinting, the paternal copy is turned off or silenced in everyone's neurons. “Neurotypical” people (with regard to AS) have the maternal UBE3A gene turned on, paternal UBE3A gene turned off.
Angelman syndrome is caused by not enough functional UBE3A protein in the brain.
People living with Angelman syndrome have a genetic difference that affects the maternal UBE3A gene. That difference results in not enough functional UBE3A protein in the brain.
Most often, this is because the maternal UBE3A gene is missing (Deletion) but it can also happen because of an error inside the gene (Mutation), because a person has two copies of the paternal UBE3A gene (Uniparental disomy (UPD)) or because the maternal UBE3A gene was incorrectly turned off (Imprinting center defect (ICD)).
These genetic differences all result in the maternal UBE3A gene being absent or nonfunctional and are referred to as genotypes in AS. Learn more about each AS genotype.
The bottom line is that when the maternal UBE3A gene is absent or nonfunctional, there is no UBE3A protein made in the brain. This is what causes Angelman syndrome.
Why does the absence of UBE3A protein in the brain cause Angelman syndrome?
UBE3A protein helps control how brain cells communicate with each other. It works by marking certain other proteins for removal, which is important for keeping our brain cells healthy and functioning properly. When UBE3A is absent, other proteins can build up, interfering with how brains cells communicate, which then affects learning and muscle control.
In most cases, Angelman syndrome isn’t inherited. Instead, the genetic differences that cause AS occur as random events during the formation of sperm or egg cells or in early embryonic development. In more rare instances, it is inherited from a parent who carries a UBE3A mutation or a chromosome difference. For more information on inheritance by specific genotype, click here.
For Genetics 201, head over to this page.