在具有父源和母源单亲二倍体（upd(14)）样表型的个体中，影响人类14q32.2印记区域的缺失和表观突变。

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

作者信息

Kagami Masayo, Sekita Yoichi, Nishimura Gen, Irie Masahito, Kato Fumiko, Okada Michiyo, Yamamori Shunji, Kishimoto Hiroshi, Nakayama Masahiro, Tanaka Yukichi, Matsuoka Kentarou, Takahashi Tsutomu, Noguchi Mika, Tanaka Yoko, Masumoto Kouji, Utsunomiya Takeshi, Kouzan Hiroko, Komatsu Yumiko, Ohashi Hirofumi, Kurosawa Kenji, Kosaki Kenjirou, Ferguson-Smith Anne C, Ishino Fumitoshi, Ogata Tsutomu

机构信息

Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.

出版信息

Nat Genet. 2008 Feb;40(2):237-42. doi: 10.1038/ng.2007.56. Epub 2008 Jan 6.

DOI:10.1038/ng.2007.56

PMID:18176563

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.

摘要

人类染色体14q32.2携带一组印记基因，包括父源表达基因（PEGs），如DLK1和RTL1，以及母源表达基因（MEGs），如MEG3（也称为GTL2）、RTL1as（RTL1反义链）和MEG8（参考文献1,2），还有基因间差异甲基化区域（IG-DMR）和MEG3-DMR。与此一致的是，14号染色体的父源和母源单亲二体性（分别为upd(14)pat和upd(14)mat）会导致不同的表型。我们研究了8名具有upd(14)pat样表型的个体（病例1 - 8）和3名具有upd(14)mat样表型但不存在upd(14)的个体（病例9 - 11），并鉴定出了影响该印记区域的各种缺失和表观突变。这些结果与最近的小鼠数据一起表明，IG-DMR对母源遗传的染色体具有重要的顺式作用调节功能，并且RTL1表达过高以及DLK1和RTL1表达降低分别与upd(14)pat样和upd(14)mat样表型相关。