title: Tissue-specific and allele-specific replication timing control in the imprinted human Prader-Willi syndrome region.
abstract: To examine the relationship between replication timing and differential gene transcription in tissue-specific and imprinted settings we have studied the replication timing properties of the human Prader-Willi syndrome (PWS) region on human chromosome 15q11-13. Interphase fluorescence in situ hybridization with an overlapping series of cosmid clones was used to map a PWS replication timing domain to a 500- to 650-kb region that includes the SNRPN gene. This PWS domain replicates late in lymphocytes but predominantly early in neuroblasts, with replication asynchrony observed in both tissues, and appears to colocalize with a genetically imprinted transcription domain showing prominent expression in the brain. A 5- to 30-kb deletion in the 5' region of SNRPN results in the loss of late replication control of this domain in lymphocytes when the deleted chromosome is inherited paternally. This potential allele-specific replication timing control region also appears to colocalize with a putative imprinting control region that has been shown previously to abolish the expression of three imprinted transcripts in this same region.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Gunaratne
authors.forename: M
authors.initials: M
authors.lastname: Nakao
authors.forename: D H
authors.initials: DH
authors.lastname: Ledbetter
authors.forename: J S
authors.initials: JS
authors.lastname: Sutcliffe
authors.forename: A C
authors.initials: AC
authors.lastname: Chinault
mesh_terms: D002478:Cells, Cultured; D002884:Chromosomes, Human, Pair 15; D004261:DNA Replication; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000235:genetics*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics*; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D017411:Ribonucleoproteins, Small Nuclear