2. Academic Validation
  3. Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes

Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes

  • Nat Genet. 2008 Feb;40(2):237-42. doi: 10.1038/ng.2007.56.
Masayo Kagami 1,  Yoichi Sekita,  Gen Nishimura,  Masahito Irie,  Fumiko Kato,  Michiyo Okada,  Shunji Yamamori,  Hiroshi Kishimoto,  Masahiro Nakayama,  Yukichi Tanaka,  Kentarou Matsuoka,  Tsutomu Takahashi,  Mika Noguchi,  Yoko Tanaka,  Kouji Masumoto,  Takeshi Utsunomiya,  Hiroko Kouzan,  Yumiko Komatsu,  Hirofumi Ohashi,  Kenji Kurosawa,  Kenjirou Kosaki,  Anne C Ferguson-Smith,  Fumitoshi Ishino,  Tsutomu Ogata
Affiliations

Affiliation

  • 1 Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
PMID: 18176563 DOI: 10.1038/ng.2007.56
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.

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