Genomic Organization of theUBE3A/E6-AP Gene and Related Pseudogenes

Abstract

TheUBE3Agene encodes the E6-AP ubiquitin–protein ligase and has recently been shown to be mutated in Angelman syndrome patients who lack 15q11–q13 deletions or chromosome 15 paternal uniparental disomy. PreviousUBE3AcDNA analysis has shown a coding region of approximately 2.6 kb and a 3′-untranslated region (UTR) of <50 bp, whereas Northern analysis has indicated mRNA sizes of 5–8 kb. We have analyzed additional cDNA clones and provide evidence for an additional 0.5 kb of 5′-UTR and >2 kb of 3′-UTR. We have established the genomic organization ofUBE3Aand the sequence of intron–exon borders. We have also mapped two highly homologous processed pseudogenes,UBE3AP1andUBE3AP2,to chromosomes 2 and 21, respectively, and determined their genomic organization. These results will form the basis for studies of mutation and imprinting ofUBE3A.