How is the paternally derived UBE3A gene silenced?

In neurons, the paternal copy (allele) of UBE3A is silenced by the process of genomic imprinting. As a result, only the maternal UBE3A allele is expressed in neurons from normal individuals (Albrecht et al., 1997; Rougeulle et al., 1997; Vu and Hoffman, 1997) (Fig.

Is UBE3A imprinted?

The ubiquitin protein E3A ligase gene (UBE3A) gene is imprinted with maternal-specific expression in neurons and biallelically expressed in all other cell types.

What protein is affected by Angelman syndrome?

Abstract. Angelman syndrome is a severe neurological disorder characterized by mental retardation, absent speech, ataxia, seizures, and hyperactivity. The gene affected in this disorder is UBE3A, the gene encoding the E6-associated protein (E6AP) ubiquitin-protein ligase.

What is the difference between Prader Willi and Angelman syndrome?

Both can also result from a structural abnormality of the imprinting center, known as an imprinting mutation. In addition, Angelman syndrome can be caused by a mutation in the gene that causes it; a comparable cause is not present in Prader-Willi syndrome since it results from abnormality in more than 1 gene.

Is UBE3A methylated?

The UBE3A gene is part of the imprinted Prader-Willi/Angelman syndrome locus (PWS/AS locus) on chromosome 15q11q13. At this locus, only the maternal allele is methylated at a CpG island, which encompasses the promoter and exon 1 of the SNRPN gene and represents the DMR of the locus.

Is UBE3A paternally imprinted?

Because the paternal allele of UBE3A is epigenetically silenced (i.e., paternally imprinted) in most neurons but not other tissues (discussed below) [9–14], maternal inactivation of UBE3A causes a nearly complete loss of UBE3A protein selectively from the brain [14, 15].

Are there different types of Angelman syndrome?

There are 4 ways that Angelman syndrome can occur. These are called genotypes. Each genotype has a different mechanism that results in AS.

What is Prader-Willi?

Prader-Willi (PRAH-dur VIL-e) syndrome is a rare genetic disorder that results in a number of physical, mental and behavioral problems. A key feature of Prader-Willi syndrome is a constant sense of hunger that usually begins at about 2 years of age.

What kind of enzyme is the UBE3A gene?

View/Edit Mouse. Ubiquitin-protein ligase E3A (UBE3A) also known as E6AP ubiquitin-protein ligase (E6AP) is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells.

Where does the UBE3A isoform go in the brain?

In typically developing humans, one of the UBE3A isoforms travels to the synapse, where neurons intersect in the brain and are told what to do. With the recent discovery, we now know the other UBE3A isoform goes to the nucleus of the neuron, where DNA is located.

How are mutations in the UBE3A gene related to Angelman syndrome?

Mutations within the UBE3A gene are responsible for some cases of Angelman syndrome and Prader-Willi syndrome. Most of these mutations result in an abnormally short, nonfunctional version of ubiquitin protein ligase E3A.

Where is UBE3A located on the paternal allele?

Silencing of Ube3a on the paternal allele is thought to occur through the Ube3a-ATS part of a lincRNA called “LNCAT”, (Large Non-Coding Antisense Transcript). The UBE3A gene is located on the long (q) arm of chromosome 15 between positions 11 and 13, from base pair 23,133,488 to base pair 23,235,220.