The human necdin gene, NDN, is maternally imprinted and located in the Prader-Willi syndrome chromosomal region.
Prader-Willi syndrome (PWS) is a neurogenetic disorder that results from the absence of a normal paternal contribution to the 15q11-13 region. The clinical manifestations of PWS are a transient severe hypotonia in the newborn period, with mental retardation, hypogonadism and obesity observed later in development. Five transcripts with exclusive expression from the paternal allele have been isolated, but none of these has been shown to be involved in PWS. In this study, we report the isolation and characterization of NDN, a new human imprinted gene. NDN is exclusively expressed from the paternal allele in the tissues analysed and is located in the PWS region. It encodes a putative protein homologous to the mouse brain-specific NECDIN protein, NDN; as in mouse, expression in brain is restricted to post-mitotic neurons. NDN displays several characteristics of an imprinted locus, including allelic DNA methylation and asynchronous DNA replication. A complete lack of NDN expression in PWS brain and fibroblasts indicates that the gene is expressed exclusively from the paternal allele in these tissues and suggests a possible role of this new gene in PWS.
Jay
P
P
Centre de Recherches de Biochimie Macromoléculaire, CNRS ERS 115, INSERM U 249, Montpellier, France.
Rougeulle
C
C
Massacrier
A
A
Moncla
A
A
Mattei
M G
MG
Malzac
P
P
Roëckel
N
N
Taviaux
S
S
Lefranc
J L
JL
Cau
P
P
Berta
P
P
Lalande
M
M
Muscatelli
F
F
D017204:Angelman Syndrome / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D019175:DNA Methylation; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009424:Nervous System Physiological Phenomena; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000235:genetics*; D014018:Tissue Distribution
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C069766:necdin; C046751:endodeoxyribonuclease XmaIII; D015252:Deoxyribonucleases, Type II Site-Specific