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Dev Cell. 2014 Feb 24;28(4):366-80. doi: 10.1016/j.devcel.2014.01.016.

Developmental dynamics and disease potential of random monoallelic gene expression.

Author information

1
Institut Curie, 26 rue d'Ulm, Paris 75248, France; Genetics and Developmental Biology Unit, INSERM U934/CNRS UMR3215, Paris 75248, France.
2
Institut Curie, 26 rue d'Ulm, Paris 75248, France; Genetics and Developmental Biology Unit, INSERM U934/CNRS UMR3215, Paris 75248, France; Bioinformatics and Computational Systems Biology of Cancer, INSERM U900, Paris 75248, France; Mines ParisTech, Fontainebleau 77300, France.
3
Institut Curie, 26 rue d'Ulm, Paris 75248, France; Bioinformatics and Computational Systems Biology of Cancer, INSERM U900, Paris 75248, France; Mines ParisTech, Fontainebleau 77300, France.
4
Institut Curie, 26 rue d'Ulm, Paris 75248, France; Genetics and Developmental Biology Unit, INSERM U934/CNRS UMR3215, Paris 75248, France. Electronic address: edith.heard@curie.fr.

Abstract

X chromosome inactivation (XCI) and allelic exclusion of olfactory receptors or immunoglobulin loci represent classic examples of random monoallelic expression (RME). RME of some single copy genes has also been reported, but the in vivo relevance of this remains unclear. Here we identify several hundred RME genes in clonal neural progenitor cell lines derived from embryonic stem cells. RME occurs during differentiation, and, once established, the monoallelic state can be highly stable. We show that monoallelic expression also occurs in vivo, in the absence of DNA sequence polymorphism. Several of the RME genes identified play important roles in development and have been implicated in human autosomal-dominant disorders. We propose that monoallelic expression of such genes contributes to the fine-tuning of the developmental regulatory pathways they control, and, in the context of a mutation, RME can predispose to loss of function in a proportion of cells and thus contribute to disease.

PMID:
24576422
DOI:
10.1016/j.devcel.2014.01.016
[Indexed for MEDLINE]
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