Department of Pediatrics Division of Genetics and Metabolism

Syndrome Gene Maps

15q11.2-q13 Region

The AS gene, UBE3A, encodes a ubiquitin ligase protein. The diagram below shows the UBE3A gene map location in chromosome region 15q11.2-q13. Blue represents paternally expressed (e.g., mono-allelic expression), red represents maternally expressed, and black rep resents bi-allelically expressed genes. The presumptive gene region of the Prader-Willi syndrome is also indicated. The 3 common breakpoints associated with AS deletions are labeled BP1,BP2 and BP3.

Angelman and Prader-Willi region, 15q11.2-q13

Angelman and Prader-Willi Gene Region

Illustration of how various genetic mechanisms can cause the two sydnromes: large chromosome deletions, imprinting defects and uniparental disomy. In the case of Angelman syndrome, mutations within the gene UBE3A can also cause the syndrome.

Angelman syndrome, prader-willi syndrome, image, diagram, UBE3A

For Angelman syndrome, the below diagram shows how the imprinting center may regulate UBE3A expression by coordinated expression of an antisense transcript.

Imprinting center control of UBE3A, Angelman syndrome

11p15.5 Region

This region contains a complex area of imprinting that is associated with the Beckwith-Wiedemann syndrome. Recently, reciprocal abnormalities in this region have been implicated as the most common cause of the Russell-Silver syndrome. This first diagram illustrates the two areas of imprinted domains within this region (a centromeric and a telomeric domain).

The diagram below indicates areas that account for the main mechanisms causing Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann mechanism

As illustrated below, segmental UPD can occur as a result of mitotic crossover. Such a mechanism can create both paternal and maternal segmental uniparental disomy.

Beckwith-Wiedemann segmental UPD mechanism

The Russell-Silver Syndrome and the 11p11.5 region

In the two diagrams illustrated below, I have indicated how loss of methylation in the telomere imprinting domain of 11p11.5 can cause the Russell-Silver Syndrome. One way of thinking about IFG2 is regulation is by considering the idea of how insulator areas govern gene expression. The telomore region at 11p11.5 is known to have such an insulator (a CTCF binding domain) at this region is sensitive to DNA methylation changes as illustrated.

Russell-Silver imprinting IGF2 mechanism