title: Genome-wide assessment of imprinted expression in human cells.
abstract: BACKGROUND
  Parent-of-origin-dependent expression of alleles, imprinting, has been suggested to impact a substantial proportion of mammalian genes. Its discovery requires allele-specific detection of expressed transcripts, but in some cases detected allelic expression bias has been interpreted as imprinting without demonstrating compatible transmission patterns and excluding heritable variation. Therefore, we utilized a genome-wide tool exploiting high density genotyping arrays in parallel measurements of genotypes in RNA and DNA to determine allelic expression across the transcriptome in lymphoblastoid cell lines (LCLs) and skin fibroblasts derived from families.
  
  
  RESULTS
  We were able to validate 43% of imprinted genes with previous demonstration of compatible transmission patterns in LCLs and fibroblasts. In contrast, we only validated 8% of genes suggested to be imprinted in the literature, but without clear evidence of parent-of-origin-determined expression. We also detected five novel imprinted genes and delineated regions of imprinted expression surrounding annotated imprinted genes. More subtle parent-of-origin-dependent expression, or partial imprinting, could be verified in four genes. Despite higher prevalence of monoallelic expression, immortalized LCLs showed consistent imprinting in fewer loci than primary cells. Random monoallelic expression has previously been observed in LCLs and we show that random monoallelic expression in LCLs can be partly explained by aberrant methylation in the genome.
  
  
  CONCLUSIONS
  Our results indicate that widespread parent-of-origin-dependent expression observed recently in rodents is unlikely to be captured by assessment of human cells derived from adult tissues where genome-wide assessment of both primary and immortalized cells yields few new imprinted loci.
authors.affiliation: McGill University and Genome Quebec Innovation Centre, 740 Dr Penfield Avenue, Montreal, Quebec, H3A 1A4, Canada.
authors.forename: Lisanne
authors.initials: L
authors.lastname: Morcos
authors.forename: Bing
authors.initials: B
authors.lastname: Ge
authors.forename: Vonda
authors.initials: V
authors.lastname: Koka
authors.forename: Kevin C L
authors.initials: KC
authors.lastname: Lam
authors.forename: Dmitry K
authors.initials: DK
authors.lastname: Pokholok
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Gunderson
authors.forename: Alexandre
authors.initials: A
authors.lastname: Montpetit
authors.forename: Dominique J
authors.initials: DJ
authors.lastname: Verlaan
authors.forename: Tomi
authors.initials: T
authors.lastname: Pastinen
mesh_terms: D000483:Alleles; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D000077209:Decitabine; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D015894:Genome, Human; D018392:Genomic Imprinting / Q000235:genetics*; D023281:Genomics; D006801:Humans
chemical_list: D000077209:Decitabine; D001374:Azacitidine