GENOMIC ORGANIZATION OF THE UBE3A E6-AP GENE AND RELATED PSEUDOGENES/

The UBE3A gene encodes the E6-AP ubiquitin-protein ligase and has rece ntly been shown to be mutated in Angelman syndrome patients who lack 1 5q11-q13 deletions or chromosome 15 paternal uniparental disomy. Previ ous UBE3A cDNA analysis has shown a coding region of approximately 2.6 kb and a 3'-untranslated region (UTR) of <50 bp, whereas Northern ana lysis 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 an d >2 kb of 3'-UTR. We have established the genomic organization of UBE 3A and the sequence of intron-exon borders. We have also mapped two hi ghly homologous processed pseudogenes, UBE3AP1 and UBE3AP2, to chromos omes 2 and 21, respectively, and determined their genomic organization . These results will form the basis for studies of mutation and imprin ting of UBE3A. (C) 1998 Academic Press.