Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease

被引：411

作者：

Tufarelli, C ^{[1
]}

Stanley, JAS ^{[1
]}

Garrick, D ^{[1
]}

Sharpe, JA ^{[1
]}

Ayyub, H ^{[1
]}

Wood, WG ^{[1
]}

Higgs, DR ^{[1
]}

机构：

[1] Univ Oxford, MRC, Mol Haematol Unit, Weatherall Inst Mol Med,John Radcliffe Hosp, Oxford OX3 9DS, England

来源：

NATURE GENETICS | 2003年 / 34卷 / 02期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/ng1157

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Nearly all human genetic disorders result from a limited repertoire of mutations in an associated gene or its regulatory elements. We recently described an individual with an inherited form of anemia (alpha-thalassemia) who has a deletion that results in a truncated, widely expressed gene (LUC7L) becoming juxtaposed to a structurally normal alpha-globin gene (HBA2). Although it retains all of its local and remote cis-regulatory elements, expression of HBA2 is silenced and its CpG island becomes completely methylated early during development. Here we show that in the affected individual, in a transgenic model and in differentiating embryonic stem cells, transcription of antisense RNA mediates silencing and methylation of the associated CpG island. These findings identify a new mechanism underlying human genetic disease.

引用

页码：157 / 165

页数：9

共 43 条

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[Anonymous], 1993, Human gene mutation

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