title: Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes.
abstract: Human chromosome 14q32.2 carries a cluster of imprinted genes including paternally expressed genes (PEGs) such as DLK1 and RTL1 and maternally expressed genes (MEGs) such as MEG3 (also known as GTL2), RTL1as (RTL1 antisense) and MEG8 (refs. 1,2), together with the intergenic differentially methylated region (IG-DMR) and the MEG3-DMR. Consistent with this, paternal and maternal uniparental disomy for chromosome 14 (upd(14)pat and upd(14)mat) cause distinct phenotypes. We studied eight individuals (cases 1-8) with a upd(14)pat-like phenotype and three individuals (cases 9-11) with a upd(14)mat-like phenotype in the absence of upd(14) and identified various deletions and epimutations affecting the imprinted region. The results, together with recent mouse data, imply that the IG-DMR has an important cis-acting regulatory function on the maternally inherited chromosome and that excessive RTL1 expression and decreased DLK1 and RTL1 expression are relevant to upd(14)pat-like and upd(14)mat-like phenotypes, respectively.
authors.affiliation: Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Kagami
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sekita
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Masahito
authors.initials: M
authors.lastname: Irie
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kato
authors.forename: Michiyo
authors.initials: M
authors.lastname: Okada
authors.forename: Shunji
authors.initials: S
authors.lastname: Yamamori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakayama
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kentarou
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Mika
authors.initials: M
authors.lastname: Noguchi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kouji
authors.initials: K
authors.lastname: Masumoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Utsunomiya
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kouzan
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Komatsu
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.forename: Kenjirou
authors.initials: K
authors.lastname: Kosaki
authors.forename: Anne C
authors.initials: AC
authors.lastname: Ferguson-Smith
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Ishino
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D019457:Chromosome Breakage; D002883:Chromosomes, Human, Pair 14; D003198:Computer Simulation; D019175:DNA Methylation; D021901:DNA, Intergenic; D005220:Fathers; D005260:Female; D017353:Gene Deletion; D018392:Genomic Imprinting; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009035:Mothers; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D062085:RNA, Long Noncoding; D012045:Regulatory Sequences, Nucleic Acid; D024182:Uniparental Disomy / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D021901:DNA, Intergenic; D036341:Intercellular Signaling Peptides and Proteins; C498907:MEG3 non-coding RNA, human; D008565:Membrane Proteins; D011506:Proteins; D062085:RNA, Long Noncoding