Identification of novel imprinted transcripts in the Prader-Willi syndromeand Angelman syndrome deletion region: Further evidence for regional imprinting control

Deletions and other abnormalities of human chromosome 15q11-q13 are associa ted with two developmental disorders, Prader-Willi syndrome (PWS) and Angel man syndrome (AS). Loss of expression of imprinted, paternally expressed ge nes has been implicated in PWS. However, the number of imprinted genes that contribute to PWS, and the range over which the imprinting signal acts to silence one copy of the gene in a parent-of-origin-specific manner, are unk nown. To identify additional imprinted genes that could contribute to the P WS phenotype and to understand the regional control of imprinting in 15q11- q13, we have constructed an imprinted transcript map of the PWS-AS deletion interval. The imprinting status of 22 expressed sequence tags derived from the radiation-hybrid human transcript maps or physical maps was determined in a reverse transcriptase-PCR assay and correlated with the position of t he transcripts on the physical map. Seven new paternally expressed transcri pts localize to an similar to 1.5-Mb domain surrounding the SNRPN-associate d imprinting center, which already includes four imprinted, paternally expr essed genes. All other tested new transcripts in the deletion region were e xpressed from both alleles. A domain of exclusive paternal expression surro unding the imprinting center suggests strong regional control of the imprin ting process. This study provides the means for further investigation of ad ditional genes that cause or modify the phenotypes associated with rearrang ements of 15q11-q13.