THE NECDIN GENE IS DELETED IN PRADER-WILLI-SYNDROME AND IS IMPRINTED IN HUMAN AND MOUSE

Human chromosome 15q11-q13 contains genes that are imprinted and expre ssed from only one parental allele, Prader-Willi syndrome (PWS) is due to the loss of expression of one or more paternally expressed genes o n proximal human chromosome 15q, most often by deletion or maternal un iparental disomy. Several candidate genes and a putative imprinting ce ntre have been identified in the deletion region, We report that the h uman necdin-encoding gene (NDN) is within the centromeric portion of t he PWS deletion region, between the two imprinted genes ZNF127 and SNR PN. Murine necdin is a nuclear protein expressed exclusively in differ entiated neurons in the brain, Necdin is postulated to govern the perm anent arrest of cell growth of post-mitotic neurons during murine nerv ous system development, We have localized the mouse locus Ndn encoding necdin to chromosome 7 in a region of conserved synteny with human ch romosome 15q11-q13, by genetic mapping in an interspecific backcross p anel. Furthermore, we demonstrate that expression of Ndn is limited to the paternal allele in RNA from newborn mouse brain, Expression of ND N is detected in many human tissues, with highest levels of expression in brain and placenta. NDN is expressed exclusively from the paternal ly inherited allele in human fibroblasts, Loss of necdin gene expressi on may contribute to the disorder of brain development in individuals with PWS.