PMID- 11157801
OWN - NLM
STAT- MEDLINE
DCOM- 20010607
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 10
IP  - 4
DP  - 2001 Feb 15
TI  - Large-scale evaluation of imprinting status in the Prader-Willi syndrome region: 
      an imprinted direct repeat cluster resembling small nucleolar RNA genes.
PG  - 383-94
AB  - Loss of paternal gene expression at the imprinted domain on proximal human 
      chromosome 15 causes Prader-Willi syndrome (PWS), a complex multiple-anomaly 
      disorder involving variable mental retardation, hyperphasia leading to obesity 
      and infantile hypotonia with failure to thrive. Although numerous paternally 
      expressed transcripts have been identified that reside in the candidate region, 
      the individual contributions to the development of PWS have not been firmly 
      established. Recent studies of mouse models carrying a cytogenetic deletion 
      suggest that paternal deficiency of the SNRPN-IPW interval is critical for 
      perinatal lethality of potential relevance to PWS. Here we determined the allelic 
      expression profiles of a total of 118 cDNA clones using monochromosomal hybrids 
      retaining either a paternal or maternal human chromosome 15. Our results 
      demonstrated a preponderance of unusual transcripts lacking protein-coding 
      potential that were expressed exclusively from the paternal copy of the critical 
      interval. This interval was also found to encompass a large direct repeat (DR) 
      cluster displaying a potentially active chromatin conformation of paternal 
      origin, as suggested by enhanced sensitivity to nuclease digestion. Database 
      searches revealed an unexpected organization of tandemly repeated consensus 
      elements, all of which possessed well-defined box C and D sequences 
      characteristic of small nucleolar RNAs (snoRNAs). Southern blot analysis further 
      demonstrated a considerable degree of phylogenetic conservation of the DR locus 
      in the genomes of all mammalian species tested, but not in chicken, Xenopus and 
      Drosophila. These findings imply a potential direct contribution of the DR locus, 
      representing a cluster of multiple snoRNA genes, to certain phenotypic features 
      of PWS.
FAU - Meguro, M
AU  - Meguro M
AD  - Core Research for Evolutional Science and Technology project, Department of 
      Molecular and Cell Genetics, School of Life Sciences, Faculty of Medicine, 
      Tottori University, Nishimachi 86, Yonago, Tottori 683-8503, Japan.
FAU - Mitsuya, K
AU  - Mitsuya K
FAU - Nomura, N
AU  - Nomura N
FAU - Kohda, M
AU  - Kohda M
FAU - Kashiwagi, A
AU  - Kashiwagi A
FAU - Nishigaki, R
AU  - Nishigaki R
FAU - Yoshioka, H
AU  - Yoshioka H
FAU - Nakao, M
AU  - Nakao M
FAU - Oishi, M
AU  - Oishi M
FAU - Oshimura, M
AU  - Oshimura M
LA  - eng
SI  - OMIM/105830
SI  - OMIM/176270
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (RNA, Small Nucleolar)
SB  - IM
MH  - Base Sequence
MH  - Blotting, Northern
MH  - Chromosomes, Artificial, Yeast/genetics
MH  - Chromosomes, Human, Pair 15/genetics
MH  - Conserved Sequence
MH  - Contig Mapping
MH  - Cosmids/genetics
MH  - Evolution, Molecular
MH  - Genomic Imprinting/*genetics
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - Multigene Family/*genetics
MH  - Prader-Willi Syndrome/*genetics
MH  - RNA, Small Nucleolar/*genetics
MH  - Repetitive Sequences, Nucleic Acid/*genetics
MH  - Transcription, Genetic
EDAT- 2001/02/07 11:00
MHDA- 2001/06/19 10:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/06/19 10:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - 10.1093/hmg/10.4.383 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2001 Feb 15;10(4):383-94. doi: 10.1093/hmg/10.4.383.