title: DDC and COBL, flanking the imprinted GRB10 gene on 7p12, are biallelically expressed.
abstract: Maternal duplication of human 7p11.2-p13 has been associated with Silver-Russell syndrome (SRS) in two familial cases. GRB10 is the only imprinted gene identified within this region to date. GRB10 demonstrates an intricate tissue- and isoform-specific imprinting profile in humans, with paternal expression in fetal brain and maternal expression of one isoform in skeletal muscle. The mouse homolog is maternally transcribed. The GRB10 protein is a potent growth inhibitor and represents a candidate for SRS, which is characterized by pre- and postnatal growth retardation and a spectrum of additional dysmorphic features. Since imprinted genes tend to be grouped in clusters, we investigated the imprinting status of the dopa-decarboxylase gene (DDC) and the Cordon-bleu gene (COBL) which flank GRB10 within the 7p11.2-p13 SRS duplicated region. Although both genes were found to replicate asynchronously, suggestive of imprinting, SNP expression analyses showed that neither gene was imprinted in multiple human fetal tissues. The mouse homologues, Ddc and Cobl, which map to the homologous imprinted region on proximal Chr 11, were also biallelically expressed in mice with uniparental maternal or paternal inheritance of this region. With the intent of using mouse Grb10 as an imprinted control, biallelic expression was consistently observed in fetal, postnatal, and adult brain of these mice, in contrast to the maternal-specific transcription previously demonstrated in brain in inter-specific F1 progeny. This may be a further example of over-expression of maternally derived transcripts in inter-specific mouse crosses. GRB10 remains the only imprinted gene identified within 7p11.2-p13.
authors.affiliation: Department of Fetal and Maternal Medicine, Institute of Reproductive and Developmental Biology, Imperial College, Faculty of Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK. M.Hitchins@ich.ucl.ac.uk
authors.forename: Megan P
authors.initials: MP
authors.lastname: Hitchins
authors.forename: Louise
authors.initials: L
authors.lastname: Bentley
authors.forename: David
authors.initials: D
authors.lastname: Monk
authors.forename: Colin
authors.initials: C
authors.lastname: Beechey
authors.forename: Jo
authors.initials: J
authors.lastname: Peters
authors.forename: Gavin
authors.initials: G
authors.lastname: Kelsey
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Ishino
authors.forename: Michael A
authors.initials: MA
authors.lastname: Preece
authors.forename: Philip
authors.initials: P
authors.lastname: Stanier
authors.forename: Gudrun E
authors.initials: GE
authors.lastname: Moore
mesh_terms: D000483:Alleles; D000818:Animals; D001973:Bromodeoxyuridine; D002453:Cell Cycle; D002455:Cell Division; D002478:Cells, Cultured; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D003598:Cytoskeletal Proteins; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D004296:Dopa Decarboxylase / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D005333:Fetus / Q000166:cytology; D051383:GRB10 Adaptor Protein; D020440:Gene Duplication; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D051379:Mice; D008840:Microfilament Proteins; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D013577:Syndrome; D014158:Transcription, Genetic
chemical_list: C096541:Cobl protein, mouse; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D018076:DNA, Complementary; C495959:Grb10 protein, mouse; D008840:Microfilament Proteins; D011506:Proteins; D051383:GRB10 Adaptor Protein; D066246:ErbB Receptors; D004296:Dopa Decarboxylase; D001973:Bromodeoxyuridine